Flow regulating device in body cavity

Abstract

The devices and methods described herein include a body cavity fluid flow conditioner that includes an upstream flow accelerator and a downstream flow reducer. The flow conditioner preferably includes one or more openings that define a gap / entrainment region that provides a path through which additional fluid is entrained from a branch lumen into a fluid flow flowing from the upstream flow accelerator to the downstream flow reducer.

Description

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS

[0002] This application claims the benefit of priority to U.S. Provisional Application Serial No. 62 / 873,755, filed on July 12, 2019, and U.S. Provisional Application Serial No. 62 / 771,559, filed on November 26, 2018, the entire contents of each of which are incorporated herein by reference. This application is related to U.S. patent application serial number 15 / 995,101 filed on May 31, 2018 (now U.S. Patent No. 10,195,406) and PCT International Application No. PCT / IB2018 / 053925 filed on May 31, 2018 (published as WO2018 / 220589), each of which claims the benefit of priority to U.S. Provisional Application Serial No. 62 / 537,067 filed on July 26, 2017 and U.S. Provisional Application Serial No. 62 / 514,020 filed on June 2, 2017, the entire contents of each of which are incorporated herein by reference. Technical Field

[0003] The present invention generally relates to devices and methods for modifying flow in body lumens, such as devices and methods for creating pressure differentials and / or entraining fluids at lumens that branch from other lumens for enhancing or regulating fluid flow to treat various disorders or diseases. Background Art

[0004] Heart failure is a physiological state in which cardiac output is insufficient to meet the demands of the body and lungs. Patients with any of the many forms of heart failure are susceptible to increased fluid accumulation in the body. Congestive heart failure (CHF) occurs when cardiac output is relatively low and the body becomes congested. CHF has many possible underlying causes, including myocardial infarction, coronary artery disease, valvular disease, and myocarditis. Chronic heart failure is associated with neurohormonal activation and altered autonomic control. Although these compensatory neurohormonal mechanisms provide valuable support to the heart under normal physiological conditions, they also play an important role in the development and subsequent progression of CHF. For example, one of the body's main compensatory mechanisms to reduce blood flow in CHF is to increase the amount of salt and water retained by the kidneys. Retaining salt and water, rather than excreting it into the urine, increases the amount of blood in the bloodstream and helps maintain blood pressure. However, a larger volume of blood also stretches the heart muscle, enlarging the heart chambers, especially the ventricles. After a certain amount of stretching, the heart's contractions weaken, and heart failure worsens. Another compensatory mechanism is vasoconstriction of the arterial system. This mechanism, similar to retaining salt and water, raises blood pressure to help maintain adequate perfusion.

[0005] The glomerular filtration rate (GFR), the rate at which the kidneys filter blood, is commonly used to quantify kidney function and, therefore, the extent of kidney disease in a patient. An individual with normal kidney function has a GFR of at least 90 mL / min with no signs of kidney damage. Progression of kidney disease is indicated by a declining GFR, with a GFR below 15 mL / min typically indicating that a patient has end-stage renal disease (ESRD), which is a complete inability of the kidneys to remove waste or concentrate urine.

[0006] In addition to the increase in total body salt and water, it has been found that the altered capacitance of the splenic venous vessels alters blood volume distribution. Reduced venous capacitance may result in a shift of fluid from the venous reservoir to the effective circulating volume / splenic circulation, thereby increasing filling pressures. This may result in clinical cardiac congestion.

[0007] Cardiovascular problems, such as but not limited to insufficient blood flow or chronic high blood pressure, can lead to fluid retention in the kidneys, chronic kidney disease, reduced GFR, renal failure or even ESRD. For example, high blood pressure is considered the second most common cause of renal failure (after diabetes). It is estimated that high blood pressure causes renal damage and reduces GFR.

[0008] Transjugular intrahepatic portosystemic shunt (TIPS or TIPSS) is an artificial channel in the liver that establishes communication between the inflowing portal vein and the outflowing hepatic vein. Typically, under the guidance of imaging, a small metal stent is placed to keep the channel open and allow the channel to carry blood draining from the intestine back to the heart while avoiding the liver. TIPS can be used to treat conditions such as portal hypertension (usually caused by cirrhosis of the liver), which often leads to intestinal bleeding, life-threatening esophageal bleeding (esophageal varices), and accumulation of fluid in the abdominal cavity (ascites), and has shown promise in treating hepatorenal syndrome. The disadvantage of TIPS is that the blood that should have been filtered by the liver bypasses the liver via the artificial channel, which can cause complications.

[0009] Therefore, it is desirable to provide devices and methods for improving blood flow to prevent disease, improve body function, and / or treat conditions that would benefit from regulated body fluid flow. For example, it is desirable to treat heart failure, treat high blood pressure, prevent kidney disease, improve kidney function, restore normal values ​​of spleen circulation, improve liver function, enhance or replace TIPS, and / or prevent blood clots from traveling through the vasculature to sensitive parts of the body such as the brain in order to prevent stroke. Summary of the invention

[0010] The present invention seeks to provide devices and methods for modifying flow in a body cavity, as described in more detail below. For example, devices and methods are provided for creating pressure differentials and / or fluid entrainment at lumens branching from other lumens for enhancing or regulating fluid flow to treat various disorders or diseases. For positioning, the device can be implanted acutely or chronically in a body cavity.

[0011] The device and method of the present invention have many applications. For example, the device can be used to reduce pressure and improve flow, thereby improving flow in narrow body cavities. It can also be used in the aortic arch to reduce the peak systolic pressure in the brain or to divert emboli to other parts of the body (such as the legs), thereby reducing the risk of stroke. The device can also be installed in a bifurcation (for example, in the brachiocephalic vessels) to reduce the peak pressure gradient or divert emboli with little energy loss.

[0012] The devices and methods of the present invention have particular application in treating blood flow to and from the kidneys. According to one embodiment, the device is configured to be installed near one of the renal arteries or near a renal vein branch in the inferior venous cavity or in one of the renal veins.

[0013] When installed in the inferior vena cava or renal vein, the device can (due to the Bernoulli effect or other factors) create an area with increased blood flow velocity and reduced pressure in the inferior vena cava or renal vein. In this way, blood can be drawn from the kidneys to the renal veins and then to the inferior vena cava, thereby improving kidney function and reducing necrotic damage to the kidneys.

[0014] When installed in or near the renal vein, the device of the present invention can improve renal function by improving the net filtration pressure, which is the glomerular capillary blood pressure - (plasma-colloid osmotic pressure + Bowman capsule hydrostatic pressure), for example 55mmHg - (30mmHg + 15mmHg) = 10mmHg. Therefore, the device and method of the present invention provide an improvement over existing therapies, such as diuretics (although the present invention can also be used in addition to diuretics), angiotensin converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs), which may have deleterious effects on renal function. When used in conjunction with current treatment modalities such as diuretics, it is expected that the device and method of the present invention will improve the response to diuretics and reduce the dose required to obtain the therapeutic benefits of such previously known therapies without the disadvantages of these existing therapies.

[0015] The devices and methods of the present invention can be used to divert blood flow from the kidneys to the inferior vena cava with little energy loss. For example, significantly greater increases in blood flow can be achieved with less energy loss due to pressure drops and other fluid factors. This flow diversion from the kidneys with little energy loss to increase blood flow is promising for treating conditions such as heart failure and / or hypertension.

[0016] Note that there is a significant difference between using an upstream nozzle without a downstream flow reducer (such as a diffuser). If only one upstream nozzle is placed in the flow path, significant energy losses occur downstream of the nozzle due to the sudden expansion of the flow. However, by using a downstream flow reducer (such as a diffuser), the energy losses can be significantly reduced. This brings another advantage: since the energy losses are significantly reduced, the additional flow flowing into the gap is effectively added to the flow from the upstream flow accelerator.

[0017] In addition, when used with a downstream flow decelerator, it is expected that the present invention provides an optimal structure for the upstream flow accelerator. For example, the distance between the outlet of the upstream flow accelerator and the inlet of the downstream flow decelerator should be less than a predetermined length to reduce the pressure at the gap between the outlet and the inlet.

[0018] When installed in the renal artery, the device can reduce the pressure applied to the kidney. Without being bound by any theory, high blood pressure may damage the blood vessels and filters in the kidneys, making it difficult to remove waste from the body. By reducing the pressure in the renal artery, the filtration rate improves. Although the perfusion pressure may be reduced, the filtration rate will increase because the overall kidney function is more efficient.

[0019] Note that the fluid flow regulator of the present invention can regulate fluid flow without any input from an external energy source such as a fan, motor, etc., and without any moving parts. The structure of the device of the present invention transfers energy from one lumen flow to another different lumen flow with minimal flow energy loss.

[0020] According to one aspect of the present invention, a device is provided for changing the flow of fluid flowing through a body cavity (e.g., the inferior vena cava) coupled with (multiple) branch lumens (e.g., (multiple) renal veins, (multiple) hepatic veins). The device includes a flow regulator configured to be positioned in the body cavity. The flow regulator preferably has an upstream component and a downstream component and defines a gap. The flow regulator can be formed as a single unit (e.g., formed by a single frame) or multiple units. The upstream component has an inlet, an outlet, and a cross-sectional flow area that preferably converges from the inlet toward the outlet. The downstream component has an inlet, an outlet, and a cross-sectional flow area that preferably diverges from the inlet toward the outlet. The gap defines a path that is connected to the branch lumen, and is preferably between the inlet of the upstream component and the outlet of the downstream component. The upstream component and the downstream component each preferably define a plurality of compartments, respectively a first plurality and a second plurality, and the first plurality of compartments can have a more flexible structure than the second plurality of compartments. For example, this can be achieved by making the average void space area of ​​the second plurality of compartments less than the average void space area of ​​the first plurality of compartments. Preferably, the void space is the area of ​​the compartment defined by the struts of the frame. For example, the struts may define a closed loop shape, such as an ellipse or a diamond or a combination thereof. The gap that may be formed by one or more openings of the entrainment region may be free of compartments, or may include a plurality of radially spaced openings disposed on the downstream component. The plurality of radially spaced openings may be parallel or angled relative to the longitudinal axis of the flow conditioner. The flow conditioner preferably accelerates the fluid flow passing through the upstream component toward the downstream component to generate a low pressure region near the gap and to entrain additional fluid into the fluid flow when the fluid flow enters the inlet of the downstream component. The inner core may be advanced into the flow conditioner to further entrain the fluid by increasing or decreasing the effective cross-sectional area of ​​the nozzle and / or diffuser.

[0021] The outlet of the upstream component is preferably spaced apart from the inlet of the downstream component by an appropriate distance to increase the flow in the branch lumen(s) while minimizing pressure loss. For example, the distance from the outlet to the inlet may be less than 15 mm.

[0022] According to one aspect, the downstream component has two divergent portions, each having a different average divergence angle. For example, the second divergent portion may have a larger average divergence angle than the first divergent portion. In one embodiment, the second divergent portion defines a third plurality of compartments, which is more flexible in structure than the second plurality of compartments. The second plurality of compartments is preferably positioned between the first plurality of compartments and the third plurality of compartments. In this way, the structure of the middle region of the flow conditioner is more rigid than the more flexible inner and outer regions. The first plurality of compartments and the third plurality of compartments may have substantially the same flexibility.

[0023] According to one aspect, the cross-sectional flow area at the outlet of the upstream component is less than the cross-sectional flow area at the inlet of the downstream component. In addition, the upstream component may include a narrowing section to allow coupling to a delivery device, which may remain coupled to the delivery device throughout the acute treatment process, or may be detached from the delivery device for chronic treatment. The downstream device may include a non-traumatic end to prevent vascular damage, leave the distal end intact, and prevent straightening during device curling. The outlet of the upstream component can be positioned downstream of the location where the branch lumen first intersects the body cavity. The gap can extend downstream from the location where the branch lumen first intersects the body cavity. The upstream component and the downstream component can share a flow axis that is colinear with the flow axis of the body cavity. The outlet of the upstream component can be positioned downstream of the inlet of the downstream component.

[0024] In one example, the upstream component is coupled to the downstream component via a fluid flow structure that defines a gap. The upstream component, the downstream component, and the fluid flow structure can be formed by a single frame. The fluid flow structure can extend outward from the upstream component and the downstream component so that the fluid flow structure contacts the inner wall of the body cavity. The joint between the fluid flow structure and the upstream component and / or the downstream component can have a curved shape, such as an S-shaped curve shape.

[0025] According to one aspect, the length of the downstream component is greater than the length of the upstream component. The average convergence angle of the upstream component may be greater than the average divergence angle of the downstream component. The upstream component may include a nozzle that accelerates the fluid flow through the upstream component, and the downstream component may include a diffuser that decelerates the fluid flow with entrained additional fluid through the downstream component.

[0026] The flow conditioner can be formed of a metal frame. The metal frame can be at least partially coated with a biocompatible material at the upstream component and the downstream component. In one example, an uncoated portion of the metal frame between the upstream and downstream components defines a gap that allows fluid from the branch lumen(s) to entrain fluid flow through the flow conditioner.

[0027] According to one aspect, a delivery device for delivering a flow regulator to a body cavity is provided. The delivery device preferably has a sheath to hold the flow regulator in a retracted state, and an inner component configured to slide within the sheath and push the flow regulator out of the sheath and into the body cavity into a deployed state.

[0028] According to another aspect, a method for changing the flow of fluid through a body cavity coupled to a branch lumen is provided. The method may include positioning a flow regulator in the body cavity, the flow regulator including an upstream component and a downstream component and defining a gap, the upstream component being positioned in a first body cavity portion and having an inlet, an outlet, and a cross-sectional flow area converging from the inlet toward the outlet, the downstream component being positioned in a second body cavity portion, and having an inlet, an outlet, and a cross-sectional flow area diverging from the inlet toward the outlet. The gap may be positioned at a position where the branch lumen intersects with the body cavity, and the outlet may be positioned downstream of a position where the branch lumen first intersects with the body cavity. The upstream component and the downstream component may each include a plurality of compartments, and the plurality of compartments of the downstream component may be harder than the plurality of compartments of the upstream component. The method may include accelerating a fluid flow passing through the upstream component toward the downstream component to generate a low pressure region near the gap, and entraining additional fluid into the fluid flow when the fluid flow enters the inlet of the downstream component. The method may also include advancing the inner core into the flow regulator to further entrain the fluid.

[0029] Positioning the flow regulator within the body cavity may include positioning the upstream component in the inferior vena cava so that the inlet is upstream of the branch of the renal vein(s), and positioning the downstream component in the inferior vena cava so that the outlet is downstream of the branch of the renal vein(s), thereby drawing blood from the renal vein(s) into the inferior vena cava and improving kidney function. Drawing blood from the renal vein(s) to the inferior vena cava to improve kidney function may further reduce excess fluid for treating heart failure.

[0030] Positioning the flow regulator within the body cavity may include positioning an upstream component in the inferior vena cava such that the inlet is upstream of the branch of the hepatic vein(s), and positioning a downstream component in the inferior vena cava such that the outlet is downstream of the branch of the hepatic vein(s), thereby cannulating blood back into the inferior vena cava and improving spleen circulation. A flow regulator positioned within the inferior vena cava at the branch of the hepatic vein(s) is expected to improve liver function and / or may replace, or be used in conjunction with, a TIPS procedure.

[0031] The flow conditioner can regulate fluid flow without any input from an external energy source. The flow conditioner can regulate fluid flow without any moving parts. For example, the gap can be a plurality of radially spaced openings that are angled relative to the longitudinal axis of the flow conditioner, such as in a spiral shape, thereby causing a rotating fluid flow pattern.

[0032] Therefore, according to an embodiment of the present invention, a system is provided, which includes a body cavity fluid flow regulator, which includes an upstream flow accelerator separated from a downstream flow reducer by a gap, wherein the gap is a path for entraining additional fluid with fluid flowing from the upstream flow accelerator to the downstream flow reducer.

[0033] A gap may be located in a fluid flow structure that defines a boundary for a path to entrain additional fluid flow toward a downstream flow reducer. The upstream flow accelerator may have a flow cross-section that converges in a downstream direction. The downstream flow reducer may have a flow cross-section that diverges in a downstream direction. The fluid flow structure may include one or more conduits that are not colinear with the flow direction from the upstream flow accelerator to the downstream flow reducer. The upstream flow accelerator and the downstream flow reducer may share a common colinear flow axis. The fluid flow structure may or may not connect the upstream flow accelerator to the downstream flow reducer. The fluid flow structure may diverge outward in a direction away from the central axis of the fluid flow structure. The junction between the fluid flow structure and at least one of the upstream flow accelerator and the downstream flow reducer may be curved.

[0034] According to an embodiment of the present invention, a method for modifying fluid flow through a body cavity is provided, the method comprising installing a fluid flow regulator in the body, the fluid flow regulator comprising an upstream flow accelerator, the upstream flow accelerator being separated from a downstream flow reducer by a gap, the upstream flow accelerator being installed in a first body cavity portion, and the downstream flow reducer being installed in a second body cavity portion, wherein when fluid flows from the upstream flow accelerator to the downstream flow reducer, additional fluid is entrained into the gap and added to the fluid flowing from the upstream flow accelerator to the downstream flow reducer.

[0035] In one approach, a fluid flow regulator is installed near the renal artery to improve kidney function by reducing renal perfusion pressure.

[0036] In one approach, a fluid flow regulator is installed near the bifurcation to divert emboli away from the bifurcation.

[0037] In one approach, a fluid flow regulator is installed in the aortic arch to reduce peak systolic pressure.

[0038] In one approach, a fluid flow regulator is installed near the hepatic vein to improve spleen circulation.

[0039] According to another aspect of the present invention, another device for changing the fluid flow of a body cavity coupled to a branch lumen is provided. The device includes a flow regulator having an upstream component and a downstream component and defining a gap. The upstream component has an inlet, an outlet, and a cross-sectional flow area converging from the inlet toward the outlet, and defines a first plurality of compartments. The downstream component has an inlet, an outlet, and a cross-sectional flow area diverging from the inlet toward the outlet, and defines a second plurality of compartments, and its structure is less flexible than the first plurality of compartments, wherein the gap defines a path communicated with the branch lumen. The gap can be positioned between the inlet of the upstream component and the outlet of the downstream component. The upstream component and the downstream component can be at least partially coated with a biocompatible material, thereby exposing the gap. In addition, the flow regulator is designed to accelerate the fluid flow passing through the upstream component toward the downstream component, to generate a low pressure area near the gap, and to entrain additional fluid into the fluid flow when the fluid flow enters the inlet of the downstream component.

[0040] In addition, the downstream component may include a first diverging portion and a second diverging portion, such that the first diverging portion is upstream of the second diverging portion. The average diverging angle of the second diverging portion may be greater than the average diverging angle of the first diverging portion. In addition, the second diverging portion may define a third plurality of compartments having a structure that is more flexible than the second plurality of compartments. The second plurality of compartments may be disposed between the first plurality of compartments and the third plurality of compartments. In addition, the first plurality of compartments and the third plurality of compartments may have substantially the same flexibility.

[0041] According to one aspect of the invention, the first plurality of compartments and the third plurality of compartments have a rhombus shape, and the second plurality of compartments have a hexagonal shape. Therefore, the average void space area of ​​the second plurality of compartments can be greater than the average void space area of ​​the first plurality of compartments and the third plurality of compartments. According to another aspect of the invention, the average void space area of ​​the first plurality of compartments and the third plurality of compartments can be greater than the average void space area of ​​the second plurality of compartments. The upstream portion can also include a narrowing section at the upstream end to allow coupling to a delivery device. For example, the narrowing section can remain coupled to the delivery device for acute treatment. In addition, the downstream component can include a non-traumatic end.

[0042] The cross-sectional flow area at the outlet of the upstream component may be smaller than the cross-sectional flow area at the inlet of the downstream component. The upstream component and the downstream component may be formed by a single frame. In addition, the length of the downstream component may be greater than the length of the upstream component. The average convergence angle of the upstream component may be greater than the average divergence angle of the downstream component. In addition, the upstream component may be a nozzle that accelerates the fluid flow through the upstream component, and the downstream component may be a diffuser that decelerates the fluid flow with entrained additional fluid through the downstream component.

[0043] The present invention may further include a delivery device for delivering a flow regulator. The delivery device includes a sheath having an inner lumen sized to accommodate the flow regulator in a collapsed delivery state during delivery, and an inner component slidably disposed within the inner lumen of the sheath to facilitate deployment from a distal end of the sheath.

[0044] According to another aspect of the present invention, a method for changing the flow of fluid through a body cavity coupled to a branch lumen is provided. The method includes positioning a flow regulator and accelerating the fluid flow through an upstream component toward a downstream component to generate a low pressure area near the gap and entrain additional fluid into the fluid flow when the fluid flow enters the inlet of the downstream component. For example, the method includes positioning the upstream component in the inferior vena cava so that the inlet is upstream of the renal vein branch, and positioning the downstream component in the inferior vena cava so that the outlet is downstream of the renal vein branch, thereby drawing blood from the renal vein and improving kidney function. Drawing blood from the renal vein to improve kidney function further reduces excess fluid to treat heart failure.

[0045] According to another aspect of the invention, the method includes positioning the upstream component in the inferior vena cava so that the inlet is upstream of the hepatic vein branches, and positioning the downstream component in the inferior vena cava so that the outlet is downstream of the hepatic vein branches, thereby drawing blood to the inferior vena cava and improving spleen circulation. The method may further include coupling the narrowed section to a delivery device for acute treatment.

[0046] According to another aspect of the present invention, another device for changing the fluid flow of a body cavity coupled to a branch lumen is provided. The device comprises an inner core having an upstream region and a downstream region, the upstream region having a first end and a cross-sectional area increasing from the first end toward the downstream region, and the downstream region having a second end and a cross-sectional area decreasing from the upstream region toward the second end. For example, the rate at which the cross-sectional area of ​​the upstream region increases from the first end toward the downstream region may be greater than the rate at which the cross-sectional area of ​​the downstream region decreases from the upstream region toward the second end. Therefore, the inner core can accelerate the fluid flow transmitted around the upstream region toward the downstream region between the inner core and the branch lumen. In one embodiment, the fluid flow only passes through the downstream region between the inner core and the branch lumen around the upstream region and does not pass through the inner core.

[0047] According to one aspect of the invention, the inner core is symmetrical about a longitudinal plane extending along the longitudinal axis of the inner core. Therefore, the diameter of the inner core changes continuously from the first end of the upstream region to the second end of the downstream region. The inner core can be completely suspended in the body cavity without contacting the inner wall of the body cavity. The region of the inner core with the largest cross-sectional area can be positioned upstream of the branch lumen. Therefore, the downstream region of the inner core can extend beyond the body cavity across the entire section where the body cavity intersects with the branch lumen. BRIEF DESCRIPTION OF THE DRAWINGS

[0048] The present invention will be more fully understood and appreciated from the following detailed description taken in conjunction with the accompanying drawings, in which:

[0049] Figure 1 is a schematic diagram of a fluid flow regulator constructed and operative in accordance with an embodiment of the present invention;

[0050] Figure 2 is a side cross-sectional view of a fluid flow regulator constructed and operative in accordance with another embodiment of the present invention;

[0051] Figure 3A-19 are schematic diagrams of various fluid flow regulators of the present invention, some of which are shown installed in various body cavities, according to embodiments of the present invention;

[0052] Fig. 20 and Fig.21 is a side view of an illustrative flow accelerator constructed in accordance with the principles of the present invention;

[0053] Fig. 22 is a schematic diagram of a fluid flow regulator according to another embodiment of the present invention and includes a pump (downstream or upstream);

[0054] Fig.23 is a schematic diagram of a fluid flow regulator installed in an aneurysm according to an embodiment of the present invention;

[0055] Fig.24 is a schematic diagram of a fluid flow conditioner according to another embodiment of the present invention, wherein an outlet nozzle of an upstream flow accelerator enters a mouth of a downstream flow decelerator;

[0056] Fig.25 is a schematic diagram of a fluid flow conditioner according to another embodiment of the present invention, which has an upstream flow accelerator, a portion of which is not in line with the downstream flow reducer but is inclined relative thereto and can be installed in a branch lumen;

[0057] Fig.26 is a schematic diagram of an inner cavity support member used with a fluid flow regulator according to another embodiment of the present invention;

[0058] Fig. 27 is a schematic diagram of a fluid flow conditioner according to another embodiment of the present invention, wherein an upstream flow accelerator and / or a downstream flow decelerator may not seal against an interior contour of a body cavity;

[0059] Fig.28 is a schematic diagram of an asymmetric transition between an upstream flow accelerator and a downstream flow decelerator according to another embodiment of the present invention;

[0060] Fig.29A and Fig.29B is a view of an upstream flow accelerator or a downstream flow decelerator, the shape of which is changeable according to another embodiment of the present invention, wherein Fig.29B is along Fig.29A A cross-sectional view taken along line BB in FIG.

[0061] Figure 30-34 is a schematic diagram of a fluid flow regulator according to an embodiment of the present invention, shown in a delivery and retrieval type configuration;

[0062] Figure 35-37E are the results of bench testing used to determine the preferred configuration of a flow conditioner constructed in accordance with the present invention;

[0063] Fig.38A is a side view of a fluid flow regulator according to another embodiment of the present invention, the regulator having a frame structure including a plurality of compartments shown on the frame structure (before the frame is formed);

[0064] Fig.38B Various void space shapes with different compliances are shown according to an aspect of the present invention;

[0065] Fig.38C yes Fig.38A A side view of a fluid flow regulator;

[0066] Fig.38D is a side view of a fluid flow regulator according to yet another embodiment of the present invention having a frame structure coated with a biocompatible material;

[0067] Figures 38E-38H Various framework structures including multiple compartments having various configurations of uncoated portions of biocompatible material are shown;

[0068] Fig.38I A frame structure including a plurality of compartments having a deployment and retrieval mechanism is shown;

[0069] Fig.38J A frame structure is shown, which includes a plurality of compartments having flexible connecting portions;

[0070] Figure 38K Shown according to Fig.38J A flexible connection portion of the frame structure of an embodiment;

[0071] Fig.39 is a schematic diagram of a fluid flow regulator according to another embodiment of the present invention, the regulator being coated with a biocompatible material;

[0072] Fig.40A and Fig.40Cis an exemplary external component of a delivery device according to an embodiment of the present invention ( Fig.40A ) and internal components ( Fig.40C ) is a side view of a

[0073] Fig.40B , Fig.40D and Fig.40E According to an embodiment of the present invention Fig.40A and Fig.40C A cross-sectional view of the internal and external components of the delivery device shown in FIG.

[0074] Fig.41 is a schematic diagram of a fluid flow regulator and a delivery device coupled together for acute treatment according to another embodiment of the present invention;

[0075] Figures 42A-42F is a schematic diagram of a method for delivering a fluid flow regulator according to another embodiment of the present invention;

[0076] Figures 43A-43F is a schematic diagram of a method of retrieving a fluid flow regulator according to another embodiment of the present invention;

[0077] Fig.44 is a schematic diagram of a fluid flow regulator having an internal device according to another embodiment of the present invention;

[0078] Fig.45 is a schematic diagram of a fluid flow regulator having an external expansion element according to another embodiment of the present invention;

[0079] Fig.46 is a schematic diagram of a fluid flow regulator having an external frame according to another embodiment of the present invention;

[0080] Fig.47 is a schematic diagram of a fluid flow regulator installed near a hepatic vein according to another embodiment of the present invention;

[0081] Fig.48A and Fig.48B FIG. 1 is a schematic diagram of a fluid flow regulator installed near both the renal vein and the hepatic vein according to another embodiment of the present invention, which may be a separate regulator ( Fig.48A ) or connected as a regulator ( Fig.48B );

[0082] Fig.49 is a schematic diagram of a fluid flow conditioner according to another embodiment of the present invention, wherein an outlet nozzle of an upstream flow accelerator enters a portion of a downstream flow decelerator;

[0083] Figures 50A-50FA method of delivering and retrieving a fluid flow regulator according to another embodiment of the present invention is shown;

[0084] Figures 51A-51C is a schematic diagram of a flow conditioner with exemplary dimensions and corresponding flow patterns according to another embodiment of the present invention;

[0085] Figures 52A-52D is a schematic diagram of a flow regulator with an opening according to another embodiment of the present invention;

[0086] Fig.52E is a schematic diagram of a flow conditioner with an opening and having an additional inner cavity space according to another embodiment of the present invention;

[0087] Figure 53F is Fig.52E A cross-sectional view of a flow conditioner;

[0088] Figures 53A-53B is a schematic diagram of a flow conditioner having an angular opening and a corresponding flow pattern according to another embodiment of the present invention;

[0089] Figures 54A-54C is a schematic diagram of a flow pattern of a flow conditioner manipulator according to another embodiment of the present invention;

[0090] Figures 55A-55C is a schematic diagram of an inner core inserted into a flow conditioner according to another embodiment of the present invention;

[0091] Figures 56A-56B is a schematic diagram of a multi-stage flow conditioner according to another embodiment of the present invention;

[0092] Figures 57A-57C is a schematic diagram of an inner core inserted into a flow conditioner according to another embodiment of the present invention;

[0093] Figures 58A-58F is a schematic diagram of an inner core inserted into a flow conditioner for use with a stent according to yet another embodiment of the present invention;

[0094] Figures 59A-59B is a schematic diagram of one or more inner cores inserted into a flow conditioner according to another embodiment of the present invention;

[0095] Fig.60A is a schematic diagram of an inner core inserted into a flow conditioner for use with a pressure transducer according to another embodiment of the present invention;

[0096] Fig.60B is a schematic diagram of a core inserted into a flow regulator for use with a pressure transducer according to another embodiment of the present invention; with an upstream balloon.

[0097] Figures 61A-61B is a schematic diagram of a self-adjustable nozzle of a flow regulator according to another embodiment of the present invention;

[0098] Figures 62A-62B is a schematic diagram of flow conditioners respectively inserted downstream and upstream according to another embodiment of the present invention;

[0099] Fig.63 is a graph of in vitro results of using a flow regulator to improve simulated RBF according to another embodiment of the present invention;

[0100] Figures 64A-64B is a schematic diagram of an inner core inserted into a flow conditioner coupled downstream and upstream, respectively, for use with a pump according to another embodiment of the present invention; and

[0101] Fig.64C According to another embodiment of the present invention, Fig.64A and Fig.64B Graph of pressure loss results for the flow conditioner described.

[0102] Fig.65 A system including a flow regulator with an external pump and control system is shown.

[0103] Fig.66 is a flow chart showing the steps for adjusting the parameters of a flow conditioner pump system. DETAILED DESCRIPTION

[0104] Devices and methods are provided for modifying flow in a body lumen for creating pressure differentials and / or inducing entrainment of fluid from branch lumens for enhancing or regulating fluid flow to treat various disorders or diseases.

[0105] refer to Figure 1 , describes a flow conditioner 10 constructed and operative in accordance with a first embodiment of the present invention.

[0106] The flow conditioner 10 includes an upstream component 12 separated from a downstream component 16 by a gap 14. The gap 14 is designed to entrain fluid into the fluid flow flowing from the upstream component 12 to the downstream component 14. As described below, the upstream component 12 and the downstream component 16 create a lower pressure area near the gap 14, which preferably entrains fluid into the fluid flow flowing through the gap 14. Fluid entrainment is caused by shear-induced turbulence. In accordance with the principles of the present invention, it is expected that such entrainment will deliver blood or other body fluids to or from an area in order to improve organ function (e.g., from (multiple) renal veins to the inferior vena cava to promote better function of (multiple) kidneys, and / or from (multiple) hepatic veins to the inferior vena cava to improve liver function, thereby treating disorders and / or diseases, such as heart failure).

[0107] The upstream component 12 has an inlet 13 and an outlet 15, and preferably has a cross-sectional flow area that converges in the downstream direction (indicated by arrow 17) along part or all of the length of the upstream component 12, such as but not limited to a nozzle. In this way, the upstream component 12 accelerates the fluid flow through the upstream component 12. The downstream component 16 has an inlet 21 and an outlet 23, and preferably has a cross-sectional flow area that diverges along part or all of the length of the downstream component 16 in the downstream direction to act as a diffuser. The downstream component 16 therefore decelerates the fluid flow through the downstream component 16. The distance between the outlet 15 and the inlet 21 is selected to generate a low pressure area near the gap 14, while minimizing the pressure loss and reducing the resistance to fluid flow from (multiple) branch lumens, such as renal blood flow. For example, as described in the following data, an excessively large distance can produce a significant pressure loss, which causes the flow to flow backward into the branch lumen. Applicants have found that using a maximum distance between the outlet 15 and the inlet 21 (e.g., less than 25 mm, and more preferably less than 15 mm when the device is deployed at the renal vein) will improve flow rates in the branch vessel(s) at relatively low pressure losses. The gap 14 also allows the flow conditioner 10 to entrain additional fluid into the fluid flow as it enters the inlet 21 of the downstream component 16.

[0108] PCT patent applications WO 2016 / 128983, WO 2018 / 029688, and WO 2019 / 097424, describe several converging and diverging structures that can be used as flow conditioners 10 according to the principles described herein, and the disclosure of each of those applications is incorporated herein by reference in its entirety. Other converging and diverging structures suitable for use according to the principles of the present invention are described herein. In addition, the present invention can be implemented with other types of converging and diverging structures, such as Stratford bevel nozzles (e.g., where the flow through the nozzle is on the edge of separation, which gives the diffuser an optimal length efficiency ratio), De Laval nozzles (e.g., asymmetric hourglass shapes), nozzles and venturis of variable cross-sectional areas, inclined nozzles and venturis, etc. The central axis of the diverging portion can be arranged to be in line with or deviate from the central axis of the converging portion.

[0109] The gap 14 may be located in the fluid flow structure 18 and define the boundaries of a path for transferring or entraining additional fluid to flow into the downstream component 16. The fluid flow structure 18 may include one or more conduits that are not co-linear with the flow direction (indicated by arrow 17) from the upstream component 12 to the downstream component 16. For example, the conduits of the fluid flow structure 18 may be perpendicular to the flow direction, may be tilted at an angle, such as a 30° angle, a 45° angle, or include any other suitable configuration.

[0110] exist Figure 1 In the embodiment of FIG. 1 , the upstream component 12 and the downstream component 16 share a common co-linear flow axis 19. However, the present invention is not limited to this configuration, and the upstream component 12 may be angled relative to the downstream component 16. The upstream component 12 and the downstream component 16 may also be placed along a continuous curved path.

[0111] The fluid flow structure 18 may or may not connect the upstream component 12 to the downstream component 16. For example, if the fluid flow structure 18 is a conduit, the fluid flow structure 18 preferably connects the upstream component 12 to the downstream component 16. However, Figure 1 The fluid flow structure 18 may not be formed by a conduit, but by two walls that are not connected to each other. In this example, the fluid flow structure 18 does not connect the upstream component 12 to the downstream component 16.

[0112] The upstream component 12, the downstream component 16, and the fluid flow structure 18 may be configured as a graft, a stent (coated or uncoated), a stent graft (coated or uncoated), etc., and formed of a biocompatible material such as stainless steel or nickel-titanium alloy. The outer profile of any of the upstream component 12, the downstream component 16, and the fluid flow structure 18 may be sealed relative to the inner wall of the body cavity (such as by expanding against it), or alternatively may not be sealed, depending on the specific application.

[0113] The size and shape of the flow regulator 10 are set to be implanted in a body cavity. In one embodiment, the flow regulator 10 can be compressed for delivery (e.g., percutaneous delivery within a delivery sheath) and expand when deployed (e.g., self-expanding when released from the end of the delivery sheath or an expandable balloon). The flow regulator 10 can be inserted into the body cavity in an antegrade or retrograde manner, and can similarly be removed in an antegrade or retrograde manner. The flow regulator 10 can be used as an acute device to be removed after a few hours / days, or as a long-term permanent device or a device that can be implanted / retrieved after a long period of time. When used as an acute device, the flow regulator 10 can remain coupled to a delivery / retrieval device, such as a sheath and / or a wire / shaft, throughout the short-term implantation process to facilitate the delivery and retrieval of the device. The flow regulator 10 can be compressible when set in the body cavity to allow periodic flushing of stagnant flow areas generated near the flow regulator 10. For example, the diameter of the flow regulator 10 can be partially or completely reduced in the body cavity to allow blood to flow through stagnant flow areas.

[0114] Preferably, once expanded, the flow regulator 10 is sized to contact the inner wall of the body cavity to anchor the flow regulator 10 within the cavity. The flow regulator 10 may be formed of one or more frames and may be coated with one or more biocompatible materials. For example, the (multiple) frames may be formed of (multiple) metals (e.g., shape memory metals) or alloys or combinations thereof (e.g., stents made of stainless steel or nickel-titanium alloys or cobalt-chromium). For some applications, the (multiple) frames may include braided stents. In the case of more than one frame, the frames may be joined together by appropriate techniques such as welding. For example, the upstream component 12 and the downstream component 16 may be formed of a common frame or two frames that may be joined prior to implantation. The flow regulator 10 may be at least partially coated with a biocompatible covering material (although they may also be used as bare metal, uncoated stents). The biocompatible material can be a fabric and / or polymer, such as expanded polytetrafluoroethylene (ePTFE), woven, knitted and / or braided polyester, polyurethane, DACRON (polyethylene terephthalate), silicone, polycarbonate urethane, or pericardial tissue from equine, bovine or porcine sources. The biocompatible coating may impede or hinder fluid flow when applied to the frame. The order of the bonding and coating process can be bonding before coating or bonding before coating. The biocompatible material can be coupled to the (multiple) frames via suturing, spraying, encapsulation, electrospinning, dipping and / or different techniques.

[0115] In a preferred embodiment, the biocompatible material is impermeable to the fluid. However, for some applications, the surface need not be impermeable, but may have a sufficiently low permeability to substantially prevent blood from flowing through the longitudinal portion of the body cavity via any flow path other than the flow channel defined by the inner surface of the flow regulator 10. For some applications, the permeability per unit length of each of the surfaces is less than 0.25 microns (i.e., between 0 and 0.25 microns), where the permeability per unit length is defined based on the following formula according to Darcy's law: k / Δx=Vμ / Δp, where k is the permeability, Δx is the length (in meters), V is the average velocity (in meters per second), μ is the fluid viscosity (in Pascal-seconds), and ΔP is the pressure difference (in Pascals).

[0116] Although the present invention is not limited by any theory, a simplified engineering explanation is now provided to aid in understanding how the upstream component 12 and the downstream component 16 operate to generate a reduced pressure at the gap 14 .

[0117] The Bernoulli equation governs the relationship between fluid velocity and pressure (ignoring height differences):

[0118]

[0119] P = Pressure

[0120] ρ = density

[0121] V = speed

[0122] 1 = Condition at the inlet (upstream component 12)

[0123] 2 = Condition at gap 14

[0124] Conservation of mass (same flow rate):

[0125] V1·A1=V2·A2

[0126] A■=flow cross section

[0127] E LOSS =Energy loss

[0128] For example, if the flow conditioner 10 is installed near a kidney with the upstream component 12 in the inferior vena cava, V1 and A1 are the velocity and flow area at the inferior vena cava, respectively.

[0129] The flow rate (V2) at the gap is designed to achieve the desired pressure reduction. For example, for a velocity of 0.5 meters per second and an area ratio of 3 times, a suction force of about 6-8 mmHg can be achieved. In the case of deployment near the kidney, it is expected to improve this pressure difference by improving the kidney perfusion pressure. The pressure will change due to the improvement of kidney flow.

[0130] In another example, the flow regulator 10 can be installed near a branch to divert emboli from the branch. In yet another example, the flow regulator 10 can be deployed in the aortic arch to reduce peak systolic pressure.

[0131] Reference now Figure 2 , depicts another version of the flow conditioner 10, wherein like elements are represented by like numerals. In this embodiment, the fluid flow structure 18 includes a central portion 20, which may be cylindrical, connecting the upstream component 12 to the downstream component 16. The fluid flow structure 18 extends outwardly from the outlet 15 of the upstream component 12 and the inlet 21 of the downstream component 16, such that the fluid flow structure 18 is sized to contact the inner wall of the body cavity. The central portion 20 may be formed with one or more holes 22 that define a gap 14 for fluid communication with the branch lumens, such that additional fluid from one or more branch lumens flows into the gap 14 and is entrained by the fluid flowing from the upstream component 12 to the downstream component 16.

[0132] Note that the joint 24 between the fluid flow structure 18 and the upstream component 12 and / or the downstream component 16 can be curved. This design can help simplify the flow and prevent the creation of local turbulence or eddies that may adversely affect pressure or flow characteristics. The fluid flow structure 18 can also diverge outward (labeled 26) in a direction away from the central axis 28 of the fluid flow structure 18. Depending on the application, this divergence can be used to produce different flow effects. The divergence also causes the upstream component 12 and the downstream component 16 to move closer to each other. For example, the joint 24 between the fluid flow structure 18 and the upstream component 12 and the downstream component 16 can be S-shaped to move the outlet 15 closer to the inlet 21 to minimize the distance between these parts of the fluid regulator 10.

[0133] like Figure 2 As best shown, using the materials described above, the fluid regulator 10 can be formed from a frame 25 and coated with a biocompatible material 27. Figure 2 , the fluid regulator 10 is formed as a single frame including an upstream component 12, a gap 14, and a downstream component 16. The upstream component 12 is coated with a biocompatible material 27 to define a fluid flow channel through the upstream component 12, so that the fluid flowing through the body cavity enters the inlet 13, accelerates through the converging portion of the upstream component 12, and exits the outlet 15 into the portion of the fluid regulator 10 having the gap 14. The low pressure area is formed by the shape of the upstream component 12 and the downstream component 16 at the gap 14. In addition, the fluid from the (multiple) branch lumens at the gap 14 is entrained into the fluid flow flowing from the outlet 15 to the inlet 21. The downstream component 16 is also coated with a biocompatible material 27 to define a fluid flow channel through the downstream component 16, so that the fluid flow from the outlet 12 enters the inlet 21 together with the additional fluid passing through the gap 14, decelerates through the diverging portion of the downstream component 16, and exits from the outlet 23 back into the body cavity. In this example, the gap 14 is created by the uncoated portion of the frame 25.

[0134] The upstream component 12 may have a fixing region 29 sized to anchor the upstream component 12 within the body cavity. The fixing region 29 is sized to contact the inner wall of the body cavity and preferably has a diameter that is equal to or slightly larger than the diameter of the body cavity. The fixing region 29 may have a constant diameter and a length suitable for anchoring the upstream component 12 in the body cavity. Similarly, the downstream component 16 may have a fixing region 30 sized to anchor the downstream component 16 within another portion of the body cavity. The fixing region 30 is sized to contact the inner wall of the other portion of the body cavity and preferably has a diameter that is equal to or slightly larger than the diameter of the portion of the body cavity. The fixing region 30 may have a constant diameter and a length suitable for anchoring the downstream component 16 in the body cavity. Preferably, the fixing regions 29 and 30 are configured to seal the fluid regulator 10 within the body cavity so that fluid only flows into the fluid channel created by the fluid regulator 10 and does not flow around the fixing regions 29 or 30.

[0135] Still refer to Figure 2 , the fluid flow structure 18 has the same diameter as the fixing areas 29 and 30, which can be positioned at the intersection between the body cavity and the (multiple) branch lumens, while the proximal and distal enhanced anchoring of the (multiple) branch lumens is adjacent. In this way, the fluid flow structure 18 forms one or more additional fixing areas (illustratively, two additional fixing areas) between the fixing areas 29 and 30. As shown in the figure, the portion of the fluid flow structure 18 coated with the biocompatible material 27 (on the opposite side of the uncoated frame 25 that defines the gap 14) is used as a fixing / sealing area. The fluid flowing in the body cavity can be captured between the outer surface of the upstream component 12 and the body cavity wall between the fixing area 29 and the upstream portion of the fluid flow structure 18. In addition, or alternatively, the fluid flowing in the body cavity can be captured between the outer surface of the downstream component 16 and the body cavity wall between the fixing area 30 and the downstream portion of the fluid flow structure 18.

[0136] Reference now Figure 3A, shows an exemplary flow regulator according to a preferred embodiment, which has symbols depicting the dimensions of the flow regulator 10. The dimensions provided with respect to FIG. 3 are implemented for an embodiment suitable for implantation in the inferior vena cava. Specifically, the inlet 13 of the upstream component 12 is configured to be disposed upstream of the branch of (multiple) renal veins, and the downstream component 16 is configured to be disposed in the inferior vena cava so that the outlet 23 is downstream of the branch of (multiple) renal veins, and the gap 14 is at the branch of (multiple) renal veins. d1 is the diameter of the outlet 15 of the upstream component 12. d1 is selected to produce a jet velocity for a given device resistance. In chronic cases, d1 can be in the range of 3.5-8 mm. In acute cases, d1 is preferably in the range of 3-7 mm. d2 is the diameter of the inlet 13 in a deployed, expanded state, and can be in the range of 12-40 mm. l1 is the length of the fixation region 29, and can be in the range of 5-30 mm. l2 is the total length of the upstream component 12, and can be in the range of 15 to 60 mm. x is the distance from the outlet 15 of the upstream component 12 to the inlet 21 of the downstream component. For x, a shorter distance from the outlet 15 to the inlet 21 will provide better performance for the downstream component 16, but will result in lower renal flow due to greater flow resistance from the renal vein(s) to the downstream component 16. The distance x is preferably selected (e.g., in the range of -5-25 mm) to provide improved renal flow rate with minimal pressure loss.

[0137] Still referring to Figure 3, the distance x can be negative because the outlet 15 of the upstream component 12 can be positioned downstream of the inlet 21 of the downstream component 16. a is the distance from the outlet 15 of the upstream component 12 to the centerline of the branch lumen, such as the right renal vein, and can be in the range of -25-25 mm. L1 is the length of the fixed area 30, and can be in the range of 5-30 mm. L2 is the total length of the downstream component 16. L2 is preferably greater than l2 because the divergent shape produces a much higher pressure loss than the converging shape. The ratio of L2:l2 can be 1:1 to 3:1. D1 is the diameter at the inlet 21 of the downstream component 16, and is preferably greater than d1. Therefore, the cross-sectional flow area at the outlet 15 of the upstream component 12 is smaller than the cross-sectional flow area at the inlet 21 of the downstream component 16. D1 is selected to receive all the fluid ejected from the outlet 15. The ratio of D1:d1 can be 1:1 to 2:1. In addition, for larger distances x, D1 should be larger to ensure that the fluid ejected from the upstream component 12 is received. D2 is the diameter of the ostium 23 in the deployed, expanded state and may be in the range of 12-40 mm.

[0138] In FIG. 3 , α is the average divergence angle in the downstream component 16 and can range from 5 degrees to 30 degrees. Preferably, the divergence angle in the downstream component 16 is less than the divergence angle in the upstream component 12 and is expected to prevent pressure loss. In addition, the area near the inlet 21 of the downstream component 16 (closer to the renal vein) should change slowly - any additional pressure loss will reduce the flow rate in the inferior vena cava and thereby reduce the effectiveness of the device. The divergence angle in the downstream component 16 can be constant or variable along the length of the downstream component 16. When the divergence angle varies along the length (e.g., as Figure 2 21 ), the divergence angle is preferably minimum (e.g., in the range of 5-30 degrees) adjacent to the inlet 21. A slow change in cross-sectional flow area adjacent to the inlet 21 is preferred because as the cross-sectional flow area increases, the fluid velocity decreases, and thus the pressure loss. Thus, the divergence angle is minimum at the inlet 21, where the fluid flow is at a maximum velocity within the downstream component 16.

[0139] Figure 3A The fluid regulator 10 may be formed from a frame defining an upstream component 12, a gap 14, and a downstream component 16. In this example, the upstream component 12 and the downstream component 16 are both coated with a biocompatible material, while the gap 14 is created by an uncoated portion of the frame.

[0140] Figure 3B The renal vein is implanted into the inferior vena cava. Figure 3A Flow regulator 10. The upstream component 12 is located in the inferior vena cava so that the inlet 13 is located upstream of the left renal vein and the right renal vein branches, and the downstream component 16 is located in the inferior vena cava so that the outlet 23 is located downstream of the renal vein branches. Although the right renal vein and the left renal vein are usually at different heights along the inferior vena cava, the gap 14 is usually located near the renal vein branches (or other branch lumens when used for other indications). For example, the gap 14 can start from the position where the renal vein first intersects with the inferior vena cava, as shown in the figure. In addition, as shown in the figure, the gap 14 can be completely set in the intersection between the renal vein and the inferior vena cava. As shown in the figure, the outlet 15 of the upstream component 12 can be located downstream of the position where the renal vein first intersects with the inferior vena cava. Therefore, blood enters the fluid regulator 10 only at the inlet 13 and the gap 14, which is downstream of the position where the branch lumen first intersects with the main lumen. As shown in the figure, the inlet 21 of the downstream component 16 can be located upstream of the position where the renal vein intersects with the end of the inferior vena cava. The flow conditioner 10 creates a reduced pressure at the gap 14 and increases the rate at which blood flows to the gap 14. Entrainment can also help deliver blood from the kidneys to the gap 14. In this way, the present invention can draw blood from the kidneys to the renal veins and then to the inferior vena cava, thereby improving kidney function, reducing necrotic damage to the kidneys, and / or treating heart failure.

[0141] Figure 4-29B Additional embodiments of flow conditioners constructed in accordance with the principles of the present invention are shown. In those figures, like elements are represented by like numerals.

[0142] exist Figure 4 In the embodiment, the flow regulator 10 and Figure 3A The fluid regulator is similarly constructed, but Figure 4 The flow regulator 10 includes one or more openings 31 to reduce the generation of stagnant flow areas. Fluid entering the fluid regulator 10 flows out of the openings 31 and into the body cavity. The openings 31 serve as flush flow channels for the fluid and may be around the entire circumference of the fluid regulator 10 or be ports. The upstream component 12 or the downstream component 16 or both (as shown) may include one or more openings 31. The openings 31 may be located on the converging portion of the upstream component 12 and / or on the diverging portion of the downstream component 16. When openings 31 are utilized, they are preferably located at least on the downstream component 16 because the downstream component 16 is preferably longer than the upstream component 12 and is therefore more prone to longer stagnant flow areas.

[0143] Figure 5 is a cross-sectional view of a fluid regulator 10 having a plurality of openings 31 that function as flushing flow passages.

[0144] Figure 6 A fluid regulator 10 is shown in which the outlet 15 of the upstream component 12 is positioned downstream of the inlet 21 of the downstream component 16. In this embodiment, the distance x is negative, and D1 is greater than d1, for example, at least 1 mm greater. Both the outlet 15 and the inlet 21 can be located downstream of the intersection of the branch lumen(s) and the body cavity.

[0145] exist Figure 7 , a method of selecting the diameter D1 at the inlet of the downstream component 16 is described. The diameter D1 is selected relative to the distance x from the outlet 15 of the upstream component 12 so as to receive all the fluid ejected from the outlet 15. For larger distances x, D1 is larger to ensure that the fluid ejected from the upstream component 12 is received.

[0146] exist Figure 8 In, similar to Figure 2 and Figure 3AThe fluid flow regulator 10 is constructed of a fluid regulator 10, although the gap 14 is set along a portion extending radially outward from the outlet 15 of the upstream component 12. The gap 14 is formed along a curved portion (e.g., S-shaped) between the fluid flow structure 18 and the outlet 15, which allows the downstream component 16 to approach the (multiple) branch lumens. In addition, the fluid flow structure 18 is located downstream of the intersection between the (multiple) branch lumens and the body cavity to provide additional anchoring support. The fluid regulator 10 can be formed by a common frame (e.g., a single bracket design), which helps control the distance x between the outlet 15 and the inlet 21. The single structure also promotes coaxial orientation, particularly for eccentric upstream and downstream components.

[0147] exist Fig. 9 In, with Figure 8 The flow conditioner 10 of FIG. 1 is similarly constructed as the flow conditioner 10 of FIG. 1 , but in this case, the downstream component 16 includes a curved portion 32 (e.g., S-shaped) that extends radially outward to contact the inner wall of the body cavity. The second curved portion in the downstream component 16 provides further radial force to enhance anchoring within the body cavity and also provides a longer diffuser for a given length. The flow conditioner 10 may also include (multiple) additional gaps so as not to block fluid flowing out of other branch vessels, such as the gap 33 at the downstream end of the downstream component 16.

[0148] Reference now Fig.10 and Fig.11 , describe a flow conditioner 10 including a gap 14 that is asymmetrically positioned relative to an upstream component 12 and a downstream component 16. In these embodiments, the gap 14 is not positioned along the axis of the main vessel between the upstream component 12 and the downstream component 16, but is instead biased toward one of the upstream component 12 and the downstream component 16. Depending on the application, Fig.10 and Fig.11 The left side structure can be deployed in the upstream direction or the downstream direction; therefore, the left side structure is marked as 12 or 16, and the right side structure is marked as 16 or 12.

[0149] Fig.12 Depicted is a configuration designed to function as either an upstream component 12 or a downstream component 16, depending on the flow direction. The structure includes a relatively wide portion 35 converging into a relatively narrow portion 36. The relatively narrow portion 36 extends into a diverging portion 37 that functions as a sealing portion.

[0150] Fig.13 Another configuration is depicted that is designed to function as either an upstream component 12 or a downstream component 16 depending on the flow direction. The structure of the converging portion 38 includes surfaces that curve backwards in opposite directions.

[0151] refer to Fig.14A and Fig. 14B, describes another embodiment suitable for use as the upstream component 12 or the downstream component 16. In this embodiment, the first bracket member 39 can be installed to have converging and diverging parts ( Fig.14A ), and then the second support member 40 can be installed above the first support member 39 to define the final converging and diverging shape. In the absence of additional support members, Fig.14A It can also be used as it is. Note that the first support member does not have to contact the second support member (diffusion support) and can be shorter than the support member shown in the drawings.

[0152] refer to Fig.15 , describes an alternative design in which the upstream component 12 is constructed of a plurality of discrete objects 41, such as spheres, balloons, rods, etc., which gradually increase in size to produce a converging effect. Similarly, the downstream component 16 can be constructed of a plurality of discrete objects 41, such as spheres, balloons, rods, etc., which gradually decrease in size to produce a diverging effect. The discrete objects 41 can optionally be covered by a membrane 42 to provide a smooth flow surface.

[0153] Fig.16 Depicted is a device installed in a body cavity 43 Figure 2 An embodiment of the flow conditioner 10 is such that the gap 14 is located at the bifurcation 44 .

[0154] Fig.17 Another embodiment of a flow conditioner 10 is depicted deployed in a body lumen 43 such that the gap 14 is located at a bifurcation 44. In this embodiment, the fluid flow structure 18 includes an extension 46 deployed in the bifurcation 44. Alternatively, an opening in the stent graft at the gap 14 may be used in place of the sleeve-like extension 46.

[0155] Fig.18 The flow conditioner of one of the embodiments is depicted mounted in the aortic arch so that the gap 14 is located at the bifurcation of the carotid artery. This mounting can be used to reduce peak pressure gradients or divert emboli away from the carotid artery with little pressure loss.

[0156] Fig.19 The flow regulator of the present invention is depicted deployed near a kidney. For example, the upstream component 12 can be installed in the inferior vena cava below (upstream) the renal vein branch, and the downstream component 16 can be installed in the inferior vena cava above (downstream) the renal vein branch. The gap 14 is located at the renal vein branch. The flow regulator 10 creates a decompression area near the gap 14 and increases the blood flow velocity at the gap 14. Entrainment can also help draw blood from the kidney into the gap. In this way, the present invention can draw blood from the kidney to the renal vein, and then to the inferior vena cava, thereby improving kidney function and reducing necrotic damage to the kidney.

[0157] Reference now Fig. 20 , describes another embodiment that is configured to be used as an upstream component or a downstream component depending on the flow direction. The structure includes an outer bracket 90 and an inner bracket 92. The outer bracket 90 can be cylindrical. The inner bracket 92 can include a relatively wide portion 93 that converges into a relatively narrow portion 94. The relatively narrow portion 94 extends into a slightly divergent portion 95 with very little energy loss. The two brackets can be joined together (for example, by welding or other suitable techniques) and at least partially coated with a coating 96 (although they can also be used as bare metal, uncoated brackets). The order of the joining and coating processes can be joining before coating or coating before joining.

[0158] Reference now Fig.21 , depicting Fig. 20 Another version of the embodiment of the invention is shown in which the outer support 90 is shorter so that the coating 96 extends over the end of the outer support 90 .

[0159] Reference now Fig. 22 , describes a flow regulator 100 according to a further embodiment of the present invention. The flow regulator 100 includes a pump 102, such as an axial flow pump, a centrifugal pump, a booster pump, a chopper pump, etc. The pump 102 can be fixed in place by a bracket, or can be coupled to a portion of the upstream component 12 or the downstream component 16. Depending on the specific application, the pump 102 can be located downstream or upstream. For example, the pump 102 can be used to increase blood flow and filtration.

[0160] Any of the foregoing embodiments of the device of the present invention may be used to divert emboli or other debris, thereby eliminating the need for the use of an additional filtering device. One example is the use of an upstream component or a downstream component to divert emboli or other debris in or near the carotid artery.

[0161] Reference now Fig.23 , an exemplary flow regulator 10 is installed in an aneurysm 101 to reduce pressure at the site of the aneurysm and reduce the risk that the aneurysm will increase in size or rupture, and may even cause the aneurysm to decrease in size. In this case, the flow regulator is expected to provide a beneficial effect even if the aneurysm is not sealed. In addition, if there are one or more side branch lumens at or near the aneurysm site, the device will not only reduce pressure, but also allow blood to flow to the side branches. In this application, the device of the present invention provides significant benefits compared to currently known circular stent grafts that may adversely block side branches. If there are no side branches, the device is expected to reduce pressure without increasing blood flow. Optionally, a filter can be used with the flow regulator to prevent embolic debris from flowing from the aneurysm to other blood vessels.

[0162] Reference now Fig.24, describes a flow conditioner 110 according to another embodiment of the present invention. The flow conditioner 110 includes an upstream component 112 having an outlet 113 and a downstream component 116 having an upstream diverging port inlet 117. The outlet 113 enters the inlet 117 and this area serves as a gap 114. The outlet 113 can be coupled to a portion of the downstream component 116 with a support 115, for example, so that the outlet 113 is centered relative to the inlet 117. Alternatively, a separate support structure (which does not obstruct the flow) can be used to support the outlet 113. The straight portion in the downstream component 116 can help axially align the flow before the flow diffuses and reduce flow separation from the diffuser wall, thereby reducing pressure losses.

[0163] Fig.24 Depicted is a flow regulator 110 deployed in a renal application. In this case, an upstream component 112 may be installed in the inferior vena cava upstream of a renal vein branch, and a downstream component 116 may be installed in the inferior vena cava downstream of a renal vein branch. An outlet 113 is also disposed downstream of a renal vein branch. Similar to Fig.19 In the embodiment of the present invention, the flow regulator 110 produces a reduced pressure at the outlet 113 in the gap 114, which increases the blood flow rate from the renal vein to the gap.

[0164] about Fig.25 , a flow conditioner 120 is described. And it includes an upstream component 122 having an outlet 123 and a downstream component 126. The upstream component 122 has a first portion 128, which is not in line with the downstream component 126, but is inclined relative to it and is installed in the branch lumen. The outlet 123 can be directed to the center of the inlet of the downstream component 126, and can be coupled to a portion of the downstream component 126 with a support 125, for example to center the nozzle relative to the inlet. Alternatively, a separate support structure (which does not hinder the flow) can be used to support the outlet 123.

[0165] Reference now Fig.26 , depicts an intraluminal support member 130, which may be a stent body that helps support the body lumen from collapsing inwardly during decompression.

[0166] exist Fig. 27 In the embodiment described herein, which may be implemented in any of the embodiments described herein, the upstream component 12 and / or the downstream component 16 may not be configured to seal against the interior contour of the body cavity, but may be spaced apart from the interior contour of the body cavity. This arrangement prevents obstruction of flow from the side branch 73. Although this configuration may produce pressure loss, it still reduces pressure compared to using only a nozzle, and it can improve flow out of the body cavity, such as improving flow out of a vein.

[0167] Fig.28It is shown that the transition between the upstream component 12 and the downstream component 16 (the area of ​​the gap 14) can be offset from the centerline CC of the body cavity. In such an embodiment, the transition between the upstream component 12 and the downstream component 16 is asymmetric relative to the centerline of the body cavity. For example, if there is only one side branch, this configuration can be advantageous - the asymmetry will favor flow from the side branch; if there are two side branches, the asymmetry will favor flow from one of the side branches.

[0168] Reference now Fig.29A and Fig.29B , describes an upstream component or downstream component 80 of a further alternative embodiment, wherein the shape of the component is adjustable. The upstream component and the downstream component 80 can be combined to form a nozzle / diffuser configuration with a gap between the nozzle / diffuser configuration, which is similar to the configuration described throughout the present disclosure. In particular, the accelerator or reducer 80 can include one or more expandable members, such as end faces 82 and 84 coupled by an intermediate member 85, an expandable balloon or sac, which can be expanded or deflated by introducing fluid into the expandable members 82 and 84 (connected to a suitable fluid source, such as water, saline, air, etc.) or withdrawing fluid therefrom. The intermediate member 85 can be a covering material and / or can be preformed (e.g., cylindrical, such as a stent) to generate radial forces on the expandable components 82 and / or 84 to produce a better seal. Changing the size of the expandable components 82 and 84 will adjust the flow characteristics through the device, such as the degree to which the device diverges or converges. Expandable members 82 and 84 may be connected by a longitudinal member 86, which may also be expandable and thus may vary in size, such as in length or thickness.

[0169] The device 80 can be deployed in a deflated state and then expanded in situ. If the upstream and downstream components are combined into one device, each expandable member can be expanded / deflated using a common lumen in the catheter or using a multi-lumen catheter separately. After the patient reaches a stable condition, the device can be deflated or expanded as needed to adapt to the changing conditions. The device can also be deflated so that it can be removed from the body. A fluid reservoir can be implanted with the device to maintain expansion of the device after installation in the body. As described above for other embodiments, the device can be maintained close to the inner walls of the body cavity or can be separated from them. The flow regulator 10 can be compressed for delivery (e.g., percutaneous delivery in a delivery sheath) and expanded once deployed (e.g., self-expanding when exposed from the distal end of the delivery sheath or expandable balloon).

[0170] Reference now Fig.30, depicting the flow regulator 10 being compressed for delivery within a sheath 150. The flow regulator 10 can be coupled to a transition portion 152 and / or a wire 154 to facilitate delivery to and / or retrieval from a body cavity. The transition portion 152 illustratively has a non-concentric conical shape to facilitate compression into the sheath 150, and is coupled to the upstream component 12, although the transition portion 152 can also be coupled to the downstream component 16. The wire 154 is coupled to the transition portion.

[0171] exist Fig.31A and Fig.31B , the flow regulator 10 is depicted in an expanded, deployed configuration outside of a sheath 150. The flow regulator 10 can be transformed into the expanded, deployed configuration when the flow regulator 10 is exposed beyond the distal end of the sheath 150. For example, the sheath 150 can be pulled proximally against a retaining plug in the sheath 150 to remove the flow regulator 10 at a target location within a body cavity (e.g., where the renal vein intersects the inferior vena cava).

[0172] The flow regulator 10 can be removed from a body cavity (e.g., the inferior vena cava). For example, the sheath can be threaded onto the wire 154, and the wire 154 can be fixed in place (e.g., ex vivo fixation of the proximal end of the wire). The sheath is then pushed toward the transition portion 152 to compress the flow regulator 10 within the sheath. The flow regulator 10 and the sheath are then removed from the patient.

[0173] Reference now Fig.32 , describes a further alternative embodiment of the flow conditioner 10. The flow conditioner 10 is similar to Figure 3A The flow regulator 10, although Fig.32 The flow regulator 10 further includes a retrieval mechanism 160. The retrieval mechanism 160 can be coupled to the proximal end of the upstream component 12. In this manner, a retrieval device, such as a hook 166, can be coupled to the retrieval mechanism 160 to pull the retrieval mechanism toward the sheath 164 to compress the flow regulator 10 into the sheath 164 for retrieval. For example, the retrieval mechanism 160 can be configured like a snare, with multiple arms coupled to the end of the upstream component 12 and coupled together near the center of the flow path within the upstream component 12. The flow component 10 can be implanted with the retrieval mechanism 160 coupled thereto, or the retrieval mechanism 160 can be coupled to the flow regulator 10 during the retrieval process.

[0174] Fig.32The flow regulator 10 also includes a retrieval mechanism 162 at the opposite end of the flow regulator, for example, the retrieval mechanism 162 is coupled to the end of the downstream component 16. The retrieval mechanism 162 works in the same manner as the retrieval mechanism 160. The use of two retrieval mechanisms can be particularly helpful when the flow regulator 10 is formed by a braided structure because the diameter of the structure decreases as the braid is extended. The retrieval mechanisms 160 and / or 162 can also be used for partial retrieval. For example, the retrieval mechanisms 160 and / or 162 can be pulled in (multiple) directions away from the gap 14 (simultaneously or at different times) to partially or completely reduce the diameter of the flow regulator 10 in the body cavity. Such a reduction will allow any stagnant flow areas created by the adjacent flow regulator 10 to be flushed out. The flow regulator 10 can then be completely removed, repositioned in the body cavity and expanded, or expanded in a previously deployed position in the body cavity.

[0175] Fig.33A and Fig.33B Hook 166 is shown coupled to retrieval mechanism 160 in a compressed state within sheath 164 and in an expanded state outside sheath 164 .

[0176] Reference now Fig.34 , describes a further alternative embodiment of a flow conditioner 10. The flow conditioner 10 is similar to Figure 3A 10, but also includes a ring 172. In this embodiment, the frame 168 is formed of a plurality of ribs and defines the upstream component 12 and the downstream component 16. The frame 168 can be formed of a shape memory material such as a shape memory metal. The frame 168 is coated with a biocompatible material 170 at the upstream component 12 and the downstream component 16 to define the flow channel, and the uncoated portion of the frame 168 therebetween defines the gap 14. The ring 172 is disposed around a portion of the frame 168 and holds the portion disposed in the frame 168 in a compressed configuration. For example, in Fig.34 In the deployed state in the middle and downward direction, the ring 172 is disposed between the upstream component 12 and the downstream component 16 around the portion of the fluid regulator so that the frame 168 forms a converging cross-sectional flow area at the upstream component 12 and a diverging cross-sectional flow area at the downstream component 16. The ring 172 is configured to move along the frame 168 to transition the portion of the frame 168 disposed within the ring 172 from an expanded state to a contracted state. The shaft 174 can be coupled to the ring 172 so that movement of the shaft 174 causes the ring 172 to move along the frame 168.

[0177] The flow regulator 10 can be delivered to a target location in a body cavity in a compressed state within a sheath. Once properly positioned, the flow regulator 10 is exposed from the sheath (e.g., by pulling the sheath proximally while holding the flow regulator 10 in place), and the flow regulator 10 self-expands into a deployed configuration. The flow regulator 10 can be partially retrieved (e.g., compressed to allow cleaning) and / or fully retrieved by moving the ring 172 proximally (e.g., by pulling the shaft 174 proximally) to compress the upstream component 12 or the downstream component 16 to a diameter suitable for insertion within the sheath. The remainder of the flow regulator 10 can then be compressed within the sheath and removed from the body via the sheath.

[0178] Fig.35 Bench tests for determining the preferred configuration of a flow regulator constructed according to the present invention are shown. In the bench test, the flow regulator is placed in the main cavity (to simulate the inferior vena cava) so that the gap is positioned in the branch lumen (to simulate the renal vein). The bench model utilizes a constant stable flow in the main branch and is connected to an overflow tank to maintain a constant physiological pressure. Water is used as the fluid, and a blood analog is used to verify the trend. A side branch tube with controlled resistance is connected to an elevated water tank (to simulate kidney filtration pressure). The resistance in the side branch is fixed at a certain rate to produce normal renal blood flow with normal net filtration pressure. As a result, when the pressure gradient between the kidney bath and the main cavity is small, the fluid flow is low.

[0179] Three pressure sensors (in Fig.35 The 100 μm flow rate was measured by a digital weight scale with a computer interface via rs232. Thus, the mass flow rate (or flow velocity, since the density can be calculated) can be measured without incurring additional pressure losses.

[0180] Fig.36 is a graph showing the results for a representative IVC flow rate of 2 liters per minute (L / min). Figures 37A-37E Renal flow in mL / min versus pressure difference in mmHg for the various configurations shown in . Data points 200 are for nozzle and diffuser configurations based on the flow conditioner principles described herein (in Fig.37E In this example, the outlet inner diameter of the upstream nozzle is 5 mm, and the inlet inner diameter of the downstream diffuser is 5.5 mm. Fig.36 As shown, the kidney flow is highest for this configuration, and the table below shows that this nozzle and diffuser configuration produces much less pressure loss than all other configurations. Data point 202 is for the single nozzle configuration (at Fig.37B). In the nozzle and diffuser configuration, the same upstream nozzle is used as the upstream nozzle.

[0181] Still refer to Fig.36 , kidney flow is lower than the nozzle / diffuser configuration, but higher than the other configurations, and the 11 mmHg pressure loss shown in the table below is significantly greater than the pressure loss of the nozzle and diffuser configuration. Data point 204 is for the baseline, which means that the device is not used (at Fig.37A ). Fig.36 In the above data, only the inventive nozzle and diffuser configuration of the present invention is significantly better than the baseline. Data point 206 is for two nozzles in the same direction (e.g. Fig.37C As shown in Fig.36 As shown, the renal flow is actually negative, which will send blood flow in the renal vein in the wrong direction. In addition, the table below confirms that the pressure loss of 22 mmHg is high. The same upstream nozzle as above is used, and the outlet inner diameter of the downstream nozzle is 5 mm. Data points 208, 210, and 212 are for two nozzles in opposite directions, and the distance between the outlet of the upstream nozzle and the inlet of the downstream nozzle is 35 mm (at Fig.37D ), 12 mm, and 4 mm. The same upstream nozzle as above was used, and the inlet inner diameter of the downstream nozzle was 5 mm. For data point 208 at a distance of 35 mm, similar to data point 206, the renal flow is actually negative, which will send blood flow in the renal vein in the wrong direction. In addition, the table below confirms that the pressure loss of 22 mmHg is high. For data points 210 and 212, the renal flow is about baseline or worse than baseline, and the pressure loss is as high as 14 mmHg.

[0182] Configuration Pressure loss [mmHg] Nozzles and Diffusers 5 nozzle 11 2 nozzles in the same direction 22 2 nozzles in opposite directions - 35mm 22 2 nozzles in opposite directions - 12mm 14 2 nozzles in opposite directions - 4mm 14

[0183] Applicants have discovered that using a maximum distance between the outlet of the upstream component and the inlet of the downstream component will improve flow rates in the branch vessel(s) with relatively low pressure losses. Too large a distance can cause significant pressure losses and can actually result in sending blood flow in the renal vein(s) in the wrong direction. In addition, other structural features of the downstream component improve renal flow with low pressure losses, such as an inner diameter at the inlet of the downstream component that is greater than the inner diameter at the outlet of the upstream component, a length of a diverging region of the downstream component that is greater than a length of a converging region of the upstream component, and / or an average diverging angle of the downstream component that is less than an average converging angle of the upstream component.

[0184] Reference now Fig.38A , depicts another embodiment of the flow conditioner 10 of the present invention. In this embodiment, the flow conditioner 10 includes an exemplary frame structure that is cut and flattened to illustrate the frame cut pattern. Fig.38A Can be shared as Figure 1 and 3AMany of the features described in the previous section are described above, and like elements are represented by like numbers. In this embodiment, the downstream component 16 has a first divergent portion 176A and a second divergent portion 176B. The first divergent portion 176A is upstream of the second divergent portion 176B. The average divergence angle of the second divergent portion 176B is preferably greater than the average divergence angle of the first divergent portion 176A.

[0185] Fig.38A The flow regulator 10 of the embodiment is preferably formed by one or more frames and may be coated with one or more biocompatible materials, as described above. Illustratively, the upstream component 12 and the downstream component 16 are defined by a frame 178. The frame 178 is preferably formed by a metal tube that is laser cut to define a plurality of compartments and then processed (e.g., heated) to form the shape of the flow regulator 10. The upstream component 12 is illustratively formed by a first plurality of compartments 178A, while the downstream component 16 is formed by two differently configured compartments. The first diverging portion 176A of the downstream component 16 may be formed by a second plurality of compartments 178B, and the second diverging portion 176B may be formed by a third plurality of compartments 178C. The second plurality of compartments 178B is preferably disposed between the first plurality of compartments 178A and the third plurality of compartments 178C. The void space may be the region of the compartments defined by the struts of the frame. For example, the struts may define a tight annular shape therein, such as an ellipse or a diamond or a combination thereof.

[0186] For clarity only, one void space 178D from each of the first plurality of compartments 178A of the upstream component 12, the second plurality of compartments 178B of the first diverging portion 176A, and the third plurality of compartments 178B of the second diverging portion 176B is shown in FIG. Fig.38A The flat portions of the frames 178 are colored to show the corresponding void space areas within the compartments. According to one aspect of the invention, the average void space area of ​​the first plurality of compartments 178A is preferably greater than the average void space area of ​​the second plurality of compartments 178B, and may be substantially the same as the average void space area of ​​the third plurality of compartments 178C. The larger void space area of ​​the first plurality of compartments 178A creates a more flexible structure than the second plurality of compartments 178B. Thus, the frame 178 may be a three-part bracket that forms a flexible / rigid / flexible configuration.

[0187] Advantageously, after implantation, the flexible region can change diameter in response to changes in vessel diameter while the more rigid portions of the stent structure remain unchanged. For example, the maximum outer diameter of the upstream component 12 and the downstream component 10 can change diameter in response to changes in vessel diameter while the shape of the intermediate section of the flow conditioner 10 (e.g., the first diverging portion 176A) does not change. In this way, the divergence angle of the first diverging portion 176A can remain unchanged even if the size of the vessel changes. Changes in vessel diameter can be measured, for example, with one or more sensors on the flow conditioner and / or using imaging guidance, such as fluoroscopy, to assess changes in diameter over time.

[0188] As an additional or alternative way to increase the rigidity of the middle section of the flow conditioner 10, the struts of the frame 178 can be wider and / or thicker than the struts at the more flexible portions of the frame 178. For example, the struts of the frame 178 can be wider and / or thicker at the sections forming the second plurality of compartments 178B than at the sections forming the first plurality of compartments 178A and / or the third plurality of compartments 178C. Additionally or alternatively, the length of the compartments formed by the struts of the frame 178 can be shortened and / or the number of compartments of a given length of the frame 178 can be reduced to increase rigidity.

[0189] According to another aspect of the invention, differently shaped compartments can be used to select the relative flexibility between the various portions of the frame. This is yet another way to form a three-part stent in a flexible / rigid / flexible configuration. For example, the flexibility of the first plurality of compartments 178A and the third plurality of compartments 178C, and the rigidity of the second plurality of compartments 178B, can be selected based on the shape of the respective void spaces defined by the struts of the frame 178 (e.g., flexible shaped compartments / rigid shaped compartments / flexible shaped compartments in the frame). For example, as Fig.38B As shown, the void spaces 178E of the compartments of the first plurality of compartments 178A and the third plurality of compartments 178C may have a diamond shape, and the void spaces 178F of the compartments of the second plurality of compartments 178B may have a hexagonal shape (e.g., an elongated hexagonal shape). Fig.38B As shown, the overall void space area of ​​void space 178F is larger than void space 178E; however, the compartment with void space 178F is stronger than the compartment with void space 178E. This is because the overall working area 171 of void space 178E is larger than the working area 173 of void space 178F. In some configurations, the working area of ​​a compartment is the area of ​​the compartment defined by the angled portions of the struts of the frame, i.e., does not include the area of ​​the compartment defined by the portions of the struts that are aligned with the longitudinal axis of frame 178. As shown in FIG. Fig.38BAs shown, the working area 171 of void space 178E is greater than the total working area 173 of void space 178F, and thus the compartment having void space 178E is more flexible than the compartment having void space 178F, and the compartment having void space 178F is more rigid than the compartment having void space 178E. Therefore, the plurality of compartments defining gap 14, such as the second plurality of compartments 178B, can have an overall larger average void space area while maintaining a desired rigidity, so that larger gaps can be formed within the respective compartments, thereby increasing the amount of flow that can be entrained through the gaps compared to the gaps within the smaller diamond-shaped compartments.

[0190] Reference again Fig.38A , the frame 178 can be coated with a biocompatible material 179 at the upstream component 12 and the downstream component 16, with the uncoated portion of the frame 178 defining a gap 14 therebetween. The multiple compartments at the uncoated portion of the frame 178 at the inlet 13 can optionally be used as a filter, for example, to prevent thrombi and / or emboli in the blood. The flow regulator 10 may also include a narrowing section 180 to allow the flow regulator 10 to remain coupled to the delivery system. The narrowing section 180 may be at the most upstream end of the flow regulator 10. The flow regulator 10 may also include a non-traumatic end 182 to prevent vessel damage and straightening during device crimping and to leave the distal end intact. The non-traumatic end 182 bends inwardly away from the inner wall of the body vessel and may be at the most downstream end of the flow regulator 10. As shown, the frame 178 can be coated with a biocompatible material 179 at a portion of the upstream component 12 (e.g., the converging portion and / or the constant diameter portion), but can be a bare metal frame at other portions (e.g., upstream of the converging portion and / or the narrowing section 180), and can be coated with a biocompatible material at a portion of the downstream component 16 (e.g., the first diverging portion 176A, the second diverging portion 176B and / or the constant diameter portion downstream of the gap 14), but can be a bare metal frame at other portions (e.g., the gap 14 and / or the non-traumatic end 182).

[0191] Reference now Fig.38C According to the preferred embodiment, Fig.38AFlow conditioner 10, where the symbols depict dimensions. d1 is the diameter of the outlet 15 of the upstream component 12. d1 is selected to produce a jet velocity for a given device distance. d1 may be in the range of 4-7 mm. I2 is the total length of the upstream component 12 and may be in the range of 15-35 mm. x is the distance from the outlet of the upstream component 12 to the inlet 21 of the downstream component. The distance x is preferably selected in the range of 2-20 mm. L2 is the total length of the downstream component 16. L2 is preferably greater than 40 because a divergent shape produces a higher pressure loss than a converging shape. The ratio of L2:l2 may be 1:1 to 3:1. D1 is the diameter at the inlet 21 of the downstream component 16 and is preferably greater than d1. D1 is preferably = (d1 + 2*X*tan(A / 2)). Therefore, the cross-sectional flow area at the outlet 15 of the upstream component 12 is smaller than the cross-sectional flow area at the inlet 21 of the downstream component 16. D1 is selected to receive all of the fluid ejected from the outlet 15. The ratio of D1:d1 can be 1:1 to 2:1.

[0192] In addition, for a larger distance x, D1 should be larger to ensure that the fluid ejected from the upstream component 12 is received. A is the average divergence angle in the first divergent portion 176A of the downstream component 16, and can be in the range of 5-20 degrees. Preferably, the divergence angle in the downstream component 16 is less than the convergence angle in the upstream component 12, as shown in the figure. This structure is expected to prevent pressure loss. B is the length between the inlet 13 and the narrowing section 180 of the upstream component 12. B can be in the range of 12-45mm. C is the length of the exposed non-traumatic end 182 and can be in the range of 3-20mm. R is the length of the second plurality of rigid compartments 178B. R is preferably <(2 / 3*l2+x+2 / 3*L2). R preferably starts at ±15mm from the nozzle mouth.

[0193] Reference now Fig.38D , a flow conditioner 10 constructed according to the principles of the present invention is provided. Specifically, Fig.38D 1 is a side view of a flow conditioner 10 having an upstream component 12 and a downstream component 16, the downstream component having a first diverging portion 176A and a second diverging portion 176B. Fig.38DAs shown, the frame of the flow conditioner 10 can be only partially covered with the biocompatible material 179, so that the multiple compartments at the inlet 13 and the multiple compartments at the gap 14 remain uncovered. Specifically, the gap 14 can be defined by the uncoated multiple compartments between the upstream component 12 and the downstream component 16. For example, the frame of the flow conditioner 10 can initially be completely coated with the biocompatible material 179, and then selected portions of the coating can be removed, for example, via cutting, melting, laser, chemical means, etc., to form the gap 14. Alternatively, the frame of the flow conditioner 10 can be selectively coated so that during the coating process, the uncoated portions define the gap 14. In addition, the pattern of the multiple uncoated compartments of the gap 14 can be selected to improve the entrainment properties of the fluid through the gap 14 when used in a blood vessel.

[0194] For example, Figures 38E-38H Various framework structures having a second plurality of compartments 178B are shown, wherein various configurations of uncoated portions of biocompatible material are represented by shaded void space areas. In some configurations, these uncoated portions define a plurality of longitudinally extending openings radially spaced about the entrainment region. In addition, as described above and as shown in Figures 38E-38I As shown, the second plurality of compartments 178B may include larger but more rigid compartment shapes (e.g., elongated hexagonal compartments), and the first plurality of compartments 178A and the third plurality of compartments 178C may include smaller but more flexible compartment shapes (e.g., diamond-shaped compartments). As will be appreciated by one of ordinary skill in the art, Fig.38E -I The frame-formed flow conditioner shown may include any of the designs described herein to provide the desired flexible / rigid / flexible configuration.

[0195] like Fig.38E As shown, the gap 14 is defined by an alternating pattern of single uncoated compartments adjacent to two adjacent uncoated compartments downstream of the single uncoated compartment. x is the distance between one end of a single coated compartment and the opposite end of two adjacent uncoated compartments. Fig.38F As shown, the gap 14 is defined by an alternating pattern of two uncoated compartments adjacent to a single uncoated compartment downstream of two adjacent uncoated compartments. x is the distance from one end of the two adjacent uncoated compartments to the opposite end of the single coated compartment. Figure 38G As shown, the gap 14 is defined by an alternating pattern of a first pair of two adjacent uncoated compartments adjacent to a second pair of two adjacent uncoated compartments downstream of the first pair of two adjacent uncoated compartments, and x is the distance from one end of the first pair of two adjacent uncoated compartments to the opposite end of the second pair of two adjacent uncoated compartments. Fig.38H As shown, the gap 14 is defined by two adjacent uncoated cell rings. x is the width of two adjacent uncoated cell rings along the longitudinal axis of the frame.

[0196] Reference now Fig.38I , the flow regulator 10 may include a deployment and retrieval mechanism 177 for facilitating deployment of the flow regulator 10 into and / or removal from the patient's body. The deployment and retrieval mechanism 177 includes a hook portion 183, which is coupled to the proximal end of the upstream component 12, such as the narrowed section 180, via a pusher 181. For example, the hook portion 183 may have a plurality of arms, which are coupled to the end of the upstream component 12 via the pusher 181. In this way, a retrieval device, such as a hook or gooseneck buckle device, can be coupled to the hook portion 183 to pull the deployment and retrieval mechanism 177 toward a sheath, such as the sheath 164 described above, to compress the flow regulator 10 into the sheath for retrieval. In addition, when a force is applied to the hook portion 183, the pusher 181 facilitates the deployment of the flow regulator 10 from a compressed state within the sheath to a deployed state outside the sheath. As will be appreciated by one of ordinary skill in the art, the hook portion 183 can be coupled to the proximal end of the upstream component and / or the distal end of the downstream component of any of the flow regulators described herein as a single component that is, for example, molded, glued, compressed, welded, etc., to a frame.

[0197] Reference now Fig.38J and 38K According to some principles of the present invention, the flow regulator 10 may include one or more flexible joints 185 to facilitate implantation in a patient having a curved IVC. Fig.38J As shown, the first plurality of compartments 178A of the upstream component 12 may include a flexible joint 185 adjacent to the inlet 13, which allows the nozzle to have less kinking at a wider bend angle of the IVC. In addition, the third plurality of compartments 178C may include a flexible joint 185 between the first diverging portion 176A and the second diverging portion 176B and along the second diverging portion 176B, for example, between the junction of the first diverging portion 176A and the second diverging portion 176B and the non-traumatic end 182. Therefore, this design will allow the downstream portion of the upstream component 12 and the upstream portion of the downstream component 16 to be less curved than other portions of the flow conditioner 10 to ensure that the jet of the fluid flow leaving the upstream component 12 is centered about the inlet of the downstream component 16.

[0198] like Figure 38K As shown, a flexible joint 185 may be positioned at the junction of two adjacent compartments. Figure 38K A frame 178 having compartment-to-compartment joints with flexible joints 185 (left) and a frame 178 having compartment joints without flexible joints therebetween are shown. As will be appreciated by one of ordinary skill in the art, the flow regulator 10 may include more or fewer flexible joints 185 along the frame to optimize implantation of the flow regulator 10 within a tortuous IVC.

[0199] Reference now Fig.39 In another embodiment of the present invention, the flow conditioner 10 is coated with a biocompatible material 179 at the upstream component 12 and the downstream component 16, and the uncoated portion of the frame 178 therebetween defines a gap 14. The average void space of the plurality of compartments at the gap 14 can be greater than the average void space of the remaining portion of the second plurality of compartments 178B to enhance the flow into the gap 14. For example, Fig.39 , the frame 178 at the gap 14 has a plurality of longitudinally extending struts that are substantially parallel to each other (and substantially parallel to the longitudinal axis of the blood vessel). Fig.39 Also shown is the flow conditioner 10 having a narrowed section 180 , but without the atraumatic end 182 .

[0200] Reference now FIG. 40A to FIG. 40E , describes an embodiment of a delivery device 184 for delivering a flow regulator 10 to a body cavity. Fig.40A and Fig.40B In the embodiment of the present invention, the delivery device 184 includes a sheath 186 having an inner lumen 188 of appropriate size to maintain the flow regulator 10 in a retracted delivery state. Fig.40C , Fig.40D and Fig.40E In the embodiment of the present invention, the delivery device 184 can also include an internal component 190 to facilitate the deployment of the flow regulator 10 through the distal end of the sheath 186. Alternatively, the delivery device 184 can include a handle 194 at the proximal end of the sheath 186 to allow the clinician to hold the sheath 186 and optionally coupled to a hose 195 for flushing the lumen 188 of the sheath 186.

[0201] In addition, the inner assembly 190 can include a tip 192 coupled to the distal end of the inner assembly 190, which is configured to be coupled to the narrowed end 180 of the flow regulator 10 during acute treatment. The inner assembly 190 can further be coupled to a handle 196 at the proximal end of the inner assembly 190. The handle 194 is configured to be grasped as the inner assembly 190 is moved distally through the sheath 186 via the handle 196, thereby pushing the flow regulator 10 through the lumen 188 to deploy the flow regulator 10 from the distal end of the sheath 186. Fig.40B and Fig.40D 186 and inner assembly 190, respectively. Fig.40E is an enlarged view of tip 192 showing the stepped configuration to enable coupling to narrowed end 180 and facilitate pushing during deployment and pulling during retrieval.

[0202] Fig.411 is an exemplary view of a flow regulator 10 and a delivery device 184 coupled together for use during acute treatment. In this case, the flow regulator 10 remains coupled to the delivery device 184 throughout the acute treatment process to facilitate retrieval of the flow regulator 10 after the treatment is completed. Illustratively, during the acute treatment, the narrowed end 180 of the flow regulator 10 is coupled to the tip 192 of the delivery device 184. Alternatively, the flow regulator 10 can be detached from the delivery device 184 and remain implanted for a certain amount of time (e.g., hours, days, months, years) for chronic treatment. If implanted, the flow regulator 10 can be retrieved, similar to the description above with respect to Figure 32-34 The way of description.

[0203] Reference now Figures 42A to 43F , depicting the deployment and retrieval of a flow regulator 10 from a delivery device 184 in a body cavity. For ease of illustration, the flow regulator 10 is shown in an uncoated form. Fig.42A A delivery device 184 is shown introduced into a body cavity, wherein a sheath 186 is positioned downstream of a branch lumen (e.g., renal vein (s), hepatic vein (s). The flow regulator 10 is disposed within a lumen 188 of the sheath 186 in a collapsed delivery state. While the flow regulator 10 is held in place, the sheath 186 is pulled proximally. FIG. 42B to FIG. 42F The flow regulator 10 is shown in a deployed configuration self-expanding from the distal end of the sheath 186 into a body lumen. Fig.42F The flow regulator 10 is shown exposed beyond the distal end of the sheath 186 in an expanded, deployed configuration. For example, the sheath 186 can be pulled proximally while the inner assembly 190 (which is coupled to the flow regulator 10) remains in place in the sheath 186 to remove the flow regulator 10 at a target location within a body cavity (e.g., where the renal vein intersects the inferior vena cava). To retrieve the flow regulator 10, the flow regulator 10 can be retracted into the sheath 186, as shown. FIG. 43A to FIG. 43F For example, the sheath 186 can be moved distally while the internal components (coupled to the flow regulator 10) remain in place to transition the flow regulator from an expanded, deployed state to a contracted state within the lumen 188 of the sheath 186. The delivery device 184 (with the contracted flow regulator 10 therein) is then moved proximally and out of the patient's body.

[0204] about Fig.44 , showing an internal device 198 inserted into the flow conditioner 10. One or more internal devices 198 may be added to the upstream component 12 and / or the downstream component 16. Preferably, the internal device(s) 198 may fit within the diameter of the flow conditioner 10 to partially block the opening(s) in the nozzle / diffuser (e.g., Figure 4 and Figure 5The opening 31 in the inner portion 198 is preferably of a constant diameter that is slightly smaller than the inner diameter at the end of the upstream component 12 and / or the downstream component 16, and then angles inwardly in a converging / diverging manner as shown.

[0205] exist Fig.45 In the embodiment of the present invention, external expansion elements 220 are positioned on the proximal and distal ends of the outer surface of the flow regulator 10. The external expansion elements 220 (e.g., balloons) can allow flushing of the no-flow zone and reduce the risk of emboli. In addition, the external expansion elements 220 can be used to control the suction level by creating a distance between the balloon and the vessel wall. The external expansion elements 220 can optionally be coupled to the conduit 221 at one or both sides, or the conduit 221 can surround the flow regulating portion.

[0206] Reference now Fig.46 , describes another embodiment of the present invention having an outer tubular frame 222 with a flow conditioner 10 mounted thereon. Fig.26 In an embodiment of the present invention, the outer tubular frame 222 can help prevent the reduction of the diameter of the body cavity during fluid removal or pressure reduction. Preferably, the flow regulator 10 is completely adapted within the outer tubular frame 222. The outer tubular frame 222 has a plurality of openings (e.g., compartments in a laser cut stent) so that blood flows through the outer tubular frame 222.

[0207] exist Fig.47 , the flow regulator 10 is shown as being installed in the inferior vena cava at the branch of the hepatic veins. Implanting the flow regulator 10 into the body cavity may include implanting the upstream component 12 into the inferior vena cava so that the inlet 13 is upstream of the branch of the (multiple) hepatic veins, and implanting the downstream component 16 into the inferior vena cava so that the outlet 23 is downstream of the branch of the (multiple) hepatic veins. The low pressure area near the gap 14 can preferably be positioned at the branch of the (multiple) hepatic veins, thereby inserting blood back into the inferior vena cava and improving splenic circulation. The flow regulator 10 implanted in the inferior vena cava at the branch of the (multiple) hepatic veins is expected to improve liver function and / or can replace the TIPS procedure, or be used in parallel with it. Advantageously, the flow regulator 10 improves liver flow to the inferior vena cava, thereby allowing blood to enter the liver for natural filtration (as opposed to the TIPS procedure in which blood bypasses the liver). The flow regulator 10, whether used in conjunction with or in place of a TIPS procedure, is expected to treat conditions such as portal hypertension (often caused by cirrhosis of the liver), which often leads to intestinal bleeding, life-threatening esophageal bleeding (esophageal varices), intra-abdominal fluid accumulation (ascites), and / or hepatorenal syndrome.

[0208] Reference now Fig.48A and Fig.48B, a fluid flow regulator 10 is shown deployed in the inferior vena cava such that its gap is in communication with the renal vein(s), and a second discrete flow regulator 10 is deployed in the inferior vena cava such that its gap is in communication with the hepatic vein(s). Fig.48B In the embodiment, a single flow regulator 10 is deployed in the inferior vena cava, extending across both the renal vein outlet(s) and the hepatic vein outlet(s). In the latter embodiment, the flow regulator 10 is formed as a single unit and is configured as two flow regulators; namely, a frame 178, two upstream components 12, two downstream components 16, and two gaps 14, each for reducing the pressure at its respective vein outlet.

[0209] Reference now Fig.49 , the flow conditioner 10 includes an upstream component 12 with an outlet 13 and a downstream component 16, the downstream component having an upstream diverging inlet 17. The outlet 13 enters the inlet 17, and this area serves as a gap 14. In this example, the upstream component 12 can be installed in the inferior vena cava upstream of the branch of (multiple) renal veins, and the downstream component 16 can be installed in the inferior vena cava downstream of the branch of (multiple) renal veins. The outlet 13 is also downstream of the branch of (multiple) renal veins. The upstream component 12 first converges and then diverges at the outlet 13 to allow more arranged and guided flow. The downstream component 16 first converges to continue to accelerate the arranged and guided flow in a more stable and unified form. The straight section in the downstream component 16 can help align the flow before the flow diffuses and reduce the flow separation from the diffuser wall, thereby reducing pressure losses. Preferably, the convergence angle is wider than the divergence angle.

[0210] Reference now Figures 50A-50F , describes the deployment and retrieval of the flow regulator 10 from a delivery device 184 in a body cavity. Fig.42A -F and Fig.43A -F, the flow regulator 10 is deployed in a body cavity. The delivery device 184 includes an end cap 224, which is part of the tip 192 at the distal end of the inner assembly 190, allowing easy insertion. By pulling the sheath 186 proximally while the flow regulator 10 and the inner assembly 190 remain in place, FIG. 50A to FIG. 50B The flow regulator 10 (shown as a metal stent with a biocompatible coating of thermoplastic polyurethane (TPU)) is shown self-expanding to a deployed configuration from the distal end of the sheath 186. Alternatively, when the sheath 186 is fixed in place, the inner assembly 190 and the flow regulator 10 can be pushed distally, thereby deploying the flow regulator 10 in the body cavity. Fig.50C and Fig.50D The inner assembly 190 is shown moved proximally to secure the flow regulator 10 for acute treatment. To retrieve the flow regulator 10, the flow regulator 10 can be retracted into the sheath 186, such as Figures 50E to 50FFor example, the sheath 186 can be moved distally while the inner assembly 190 remains in place to transition the flow regulator 10 from an expanded, deployed state to a contracted state within the sheath 186. The delivery device 184 can then be moved proximally and out of the patient's body.

[0211] Reference now Figures 51A-51C , further alternative embodiments of the flow conditioner of the present invention are described. Fig.51A , the flow regulator 10 is annotated with symbols depicting dimensions according to a preferred embodiment. Exemplary dimensions according to some embodiments are similar to those described above with respect to Figure 3A Similar to those described. inlet is the total length of the upstream component 12. orifice is the distance from the outlet 15 of the upstream component 12 to the inlet 21 of the downstream component 16. diffuser is the length of the diverging portion of the downstream component 16. The diverging angle α / 2 is smaller than the converging angle β / 2. Therefore, the converging region L inlet The length can be smaller than the divergence area L diffuser Both of these angles may vary along the longitudinal axis of the flow conditioner 10, thereby allowing the flow to converge more smoothly and then diverge with minimal flow separation and energy loss (ie, shaped according to the Stratford curve). diffuser-out is the diameter of the second diverging portion 176B, and D outlet is the distal diameter of the flow conditioner 10. Length L diffuser Can be short enough so that D diffuser-out Less than D outlet , or long enough so that D diffuser-out Equal to D outlet . D nozzle is the diameter of the outlet 15 of the upstream component 12. D diffuser-in is the diameter at the inlet 21 of the downstream component 16. D diffuser-in Equal to or greater than D nozzle .

[0212] like Fig.51B and Fig.51C As depicted, the diffuser inlet area is larger than the nozzle outlet area, allowing more renal blood flow (RBF) to enter the diffuser without competing for space with the IVC jet. The RBF can enter the diffuser at inlet 21 and surround the IVC flow, creating a "ring" flow. Mixing of the two flows gradually occurs downstream. Importantly, the RBF also acts as a diffuser itself to some extent, thereby "buffering" the IVC flow.

[0213] Reference now Figures 52A-52D, a further alternative embodiment of the flow conditioner 10 includes openings 226. The openings 226 are in the form of a plurality of longitudinal through-wall slits radially disposed about the flow conditioner 10 in an entrainment region between the inlet of the upstream component 12 and the outlet of the downstream component 16. For example, the entrainment region may be integrally formed in the downstream component 16 or the upstream component 12, or both. The openings from the slits form a gap that allows fluid to be entrained into the flow conditioner 10 between the inlet of the upstream component and the outlet of the downstream component. The plurality of longitudinal slits are constructed in the downstream component 16 so that the IVC jet is confined and manipulated by the diffuser, exposing the RBF to the low pressure of the IVC jet and providing additional cross-sectional area in the diffuser for the RBF due to the divergence angle α / 2 of the diffuser. The slits may be formed in an entrainment region of the device that has the same divergence angle from the inlet 21 to the outlet 23 as the downstream component 16. In this manner, the opening formed by the longitudinal slit extends radially away from the central longitudinal axis so that the distance between the opening and the axis increases gradually as the opening 226 extends from the inlet 21 to the outlet 23. This design maintains the Figures 51A-51C The benefits described for the embodiments of FIG. 1 are achieved while creating less drag for the RBF and without compromising the effect of the diffuser on the IVC jet. Fig.52B 2 is a cross-sectional view of the flow conditioner 10 showing the RBF entering the opening 226 in a manner that reduces turbulence and / or interference with IVC flow in the entrainment region and downstream components. The entrainment region can be formed by a frame coated with a biocompatible material, leaving the opening exposed so that fluid can enter the flow conditioner 10 through the opening. The entrainment region can be coated 5-80%, preferably 20-60%, to effectively stabilize the flow. For example, a 12mm nozzle perimeter can have more than 25% coating, or 3mm from the perimeter can be completely coated. The perimeter coating can be maintained at more than 25% of the total area of ​​the flow conditioner 10. As shown in FIG. Fig.52C and Fig.52D As shown, the length L of the diffuser upper opening 226 is orifice Can be along L diffuser Extended to improve the diffuser D outlet Flushing of the entire diameter and thus preventing recirculation areas. For example, L orifice It can be 5-40 mm, preferably 8-25 mm. A larger divergence angle α / 2 can also be used without flow separation and similar diffusers.

[0214] Reference now Fig.52E and Fig.52F According to some principles of the present invention, the flow conditioner 10 may include an additional inner cavity space 187 adjacent to the opening 226. Specifically, as Fig.52FAs shown, the area of ​​the downstream component 16 having the opening 226 bulges outwardly to provide additional cavity space 187 to the flow regulator 10 in the expanded state, thereby allowing less resistance to renal flow as renal blood gradually enters the main cavity of the flow regulator 20 through the opening 226. Therefore, the downstream component 16 can have a narrower diffuser angle, thereby producing a less disturbed flow. Fig.52E The dashed line in shows the diameter of the downstream component 16 due to the bulge at the opening 226 .

[0215] Reference now Figures 53A-53B , the openings 226 may be angled relative to the longitudinal axis of the flow conditioner 10, wherein the spiral or helical openings induce a swirling flow pattern of the RBF in the diffuser, thereby creating greater flow stability and reducing flow disturbances.

[0216] Figures 54A-54C The manipulation of the IVC jet pattern by the convergence angle β / 2 is depicted, which is expected to improve the efficiency of the diffuser and improve the entrainment of the RBF. Fig.54A The convergence angle β / 2 produces an effect called “vein constriction”, where the minimum diameter of the jet D jet Smaller than the nozzle diameter D nozzle , and thus achieve a faster divergence of the IVC jet. In contrast, a sharper convergence angle can be used to achieve a more streamlined and stable IVC jet, such as Fig.54B As shown. Fig.54C In , the IVC jet is manipulated to induce a swirling flow (circumferential velocity component), which can be achieved, for example, by adding small fins to the lumen side of the device.

[0217] Reference now Figures 55A-55C , describes another alternative embodiment of the flow regulator, wherein the inner core 228, 229 is inserted into the flow regulator 10. Fig.55AIn the embodiment of the present invention, when the nozzle upstream is positioned in the upstream part 12, the inner core 228 can adjust the effective nozzle size. Therefore, the inner core 228, 229 can act as a plug around which the fluid flows. Therefore, the inner core 228 can be used to maximize the device efficacy. For example, the inner core 228 is pushed downstream toward the nozzle to reduce the cross-sectional area of ​​the nozzle, and a stronger fluid pressure is achieved in the nozzle area to reduce, and a better suction is produced (i.e. when the IVC flows relatively low and requires a larger suction pressure). The inner core 228 is moved upstream away from the nozzle to increase the effective nozzle size, and the suction pressure in the nozzle is reduced. However, when the starting position of the inner core 228 is too far upstream, there is almost no effect on the flow, and when the inner core 228 moves to too close to the nozzle, the IVC flow rate may be reduced, thereby reducing the device efficacy. For acute applications, the inner core 228 can be arranged on the tip of the in vivo catheter (not shown) so that the axial position of the inner core 228 can be controlled by advancing or retracting the catheter tip. For chronic applications, the inner core 228 may be suspended in the upstream component 12 using a stent-like support that engages the interior surface of the upstream component and includes arms that extend radially inwardly to engage and support the inner core.

[0218] Alternatively, in Fig.55B In the embodiment, an inner core 229 similar in design to the inner core 228 (with its tapered tip facing upstream) may be disposed in the distal end of the downstream component 16 to manipulate the effective angle α / 2 of the diffuser, thereby enhancing the IVC and RBF flows. Fig.55C As shown, the inner cores 228, 229 may also be provided in both the upstream component 12 and the downstream component 16. The adjustability of the inner cores 228, 229 allows the flow regulator 10 to be compatible with all patients regardless of their flow rate and may be beneficial for both acute and chronic applications.

[0219] Reference now Fig.56A and Fig.56B , the multi-stage flow conditioner 230 is depicted as having an intermediate nozzle and a diffusion section disposed between the upstream and downstream components of the flow conditioner of the present invention. By using two or more ejectors in series in the multi-stage flow conditioner 230, a converging-diverging flow pattern can be obtained. Fig.56A As depicted, the regulator 230 includes a single gap 232 through which the RBF is entrained, although multiple gaps may be provided for the RBF, such as Fig.56B For example, the gap 232 may alternatively be disposed between upstream diverging-converging components and / or between downstream converging-diverging components to achieve a desired rate of suction and flow.

[0220] Reference now Figures 57A-57CAccording to aspects of the present invention, an inner core 234, such as a balloon, is shown deployed in the lumen of the IVC at the level of the renal vein. The inner core 234 can be a compliant, non-compliant, or rigid body. The inner core 234 reduces the cross-sectional area of ​​the IVC, accelerates the flow between the inner core 234 and the IVC wall, and reduces the local fluid pressure. Therefore, the driving pressure of the entrained RBF is increased. Advantageously, the inner core 234 is simple in design and its shape can be changed in the downstream direction to adapt to the flow. For example, the inner core 234 can be longer, with its tail edge reaching the hepatic vein area without blocking the flow of other veins that flow into the IVC. In addition, the diameter of the inner core 234 can be changed, so it is easy to adjust the cross-sectional area, and then change the pressure and improve performance.

[0221] like Fig.57A As shown, the inner core 234 may have an upstream region and a downstream region. The upstream region has a first end, for example, the most upstream point of the inner core 234, and a cross-sectional area that increases from the first end toward the downstream region, so that the upstream region of the inner core 234 diverges in the direction of the IVC flow. The downstream region has a second end, for example, the most downstream point of the inner core 234, and a cross-sectional area that decreases from the upstream region toward the second end, so that the downstream region of the inner core 234 converges in the direction of the IVC flow. In addition, the inner core 234 can be symmetrical around a longitudinal plane extending along the longitudinal axis of the inner core 234. The thickness or diameter of the inner core 234 can continuously change from the first end to the second end along the longitudinal axis of the inner core 234, with the largest cross-sectional area at the junction of the upstream region and the downstream region.

[0222] Since the fluid flow passing around the inner core 234 in the blood vessel will have the maximum velocity at the maximum cross-sectional area of ​​the inner core 234, this will also be the area where the inner core 234 has the maximum friction. Therefore, the thickness or diameter of the inner core 234 that changes continuously in the direction of fluid flow provides a more effective fluid flow regulation while reducing pressure losses and not reducing IVC flow. In contrast, the constant thickness or constant diameter portion of the inner core 234 will significantly increase pressure losses and cause a reduction in IVC flow, which will result in a smaller maximum flow rate and an overall less efficient flow regulator. Preferably, the inner core 234 does not have a constant thickness or constant diameter portion, or alternatively, the inner core 234 has a constant thickness or constant diameter of up to 15 mm.

[0223] like Fig.57A As shown, the rate of increase of the cross-sectional area of ​​the upstream region may be greater than the rate of decrease of the cross-sectional area of ​​the downstream region, which allows the inner core 234 to accelerate the flow of fluid passing through the upstream region between the inner core 234 and the branch lumen toward the downstream region (e.g., where the right and left renal veins intersect the IVC). Fig.57AAs shown, the maximum cross-sectional area of ​​the inner core 234 can be positioned upstream of the branch lumen. Therefore, the angled convergent downstream portion of the inner core 234 extends throughout the entire branch lumen portion of the blood vessel. This allows more renal blood to be entrained into the IVC because the effective lumen area between the inner core 234 and the inner wall of the blood vessel increases when approaching the renal vein orifice, and allows additional lumen area to allow the renal vein flow to join the IVC branch without competing with the IVC flow. Therefore, the renal vein is still exposed to reduced flow at its outlet, but the interference between the two merged flows is minimal. In contrast, the constant thickness or constant diameter portion of the inner core 234, which has the largest overall cross-sectional area, will provide a small effective lumen area for the renal flow to join the IVC flow, and the renal flow and the IVC flow will compete on the same narrow lumen.

[0224] The inner core 234 can block the blood flow in the blood vessel lumen, so that the blood cannot flow through the inner core 234, thereby forcing the blood to flow only around the inner core 234. The inner core 234 can be completely suspended in the blood vessel lumen without contacting any part of the inner wall of the blood vessel. Fig.57A As shown, the downstream region of the inner core 234 may include a first convergent region and a second convergent region downstream of the first convergent region. The cross-sectional area of ​​the first convergent region decreases at a slower rate from the upstream region of the inner core 234 to the second divergent region of the downstream region of the inner core 234 than the cross-sectional area of ​​the second divergent region of the downstream region of the inner core 234.

[0225] Fig.57B is an elevational view of an inner core 234 disposed within the lumen of the IVC, allowing flow around the entire circumference of the device. Fig.57C The alternative inner core 235 configuration depicted in contacts the IVC wall along most of its circumference and instead leaves a channel adjacent to the renal vein outlet, thereby focusing IVC flow adjacent to the renal vein ostium. Such a shape can be created using a non-axisymmetric stent in which a low-pressure balloon or a multi-chamber balloon is deployed.

[0226] exist Figures 58A-58F The following describes the deployment of Figures 57A-57CThe structure of the inner core 234. The inner core 234 can be set in a stent 236, which can be deployed in the IVC in chronic or acute applications. The stent 236 centers the device 234 in the lumen of the IVC and can reduce the risk of collapse of the IVC wall due to reduced pressure. The stent 236 can also be used to support the IVC from narrowing due to suction pressure caused by flow regulation. In addition, the stent 236 can be used to selectively increase or decrease the diameter of the vessel, thereby determining the flow that needs to be increased. The stent 236 can have a tapered geometry that enables the inner core 234 to be fixed at different points along the contour of the inner core 234. The stent 236 can allow better control of the space between the vessel wall and the inner core 234. This control can be beneficial to pre-define the performance of the device. The stent 236 can further be used to provide a precise predetermined distance between the inner core 234 and the inner wall of the vessel. Since the inner wall of the IVC is not a perfect circle and does not have a constant area, a rigid stent can provide a controlled surface area.

[0227] exist Fig.58C , an alternative embodiment of stent 237 is described, wherein stent 237 may be a pre-deployed recaptureable stent into which core 234 is expanded at a later stage to achieve the lumen contour. Fig.58D , an alternative embodiment suitable for acute applications is described in which stent 237 can be coupled to an intracorporeal guidewire 238 at end 239 to secure stent 237 and inner core 234 within the vessel. Stent 236 can be deployed as a single unit, or stent 236 can be deployed in the IVC vessel and inner core 234 can be introduced at a later stage. In addition, as Fig.58E and Fig.58F As shown, more than one stent 237a, 237b can be located proximal and distal to the inner core 234 and positioned in the vessel as a single unit. Once positioned, the inner core 234 can be expanded.

[0228] exist Figures 59A-59B Other alternative designs for securing the inner core 234 within the IVC are described in . For example, the inner core 234 may be formed of two balloons of approximately equal volume that contact each other in the central region of the vessel, thereby firmly positioning the device within the IVC while achieving both IVC flow and enhanced renal flow. Fig.59A In FIG. 1 , a cross-sectional view of two balloons, balloon A and balloon B, is depicted, each forming a semicircle when in contact in a flattened region, creating a gap for blood flow. Fig.59B In FIG. 2 , the inner core 234 includes a main balloon A, and is secured within the IVC by securing balloons B, C, and D. For example, some of the balloons may be more compliant than others, and thus conform to the shape of the IVC more than less compliant balloons.

[0229] Reference now Fig.60A, describes a further alternative embodiment of the flow regulator of the present invention, wherein the flow regulator is coupled to a guidewire 240 and includes pressure sensors disposed on either side of the flow regulator. The guidewire 240, which may alternatively be a multi-lumen catheter, includes two pressure transducers 242, 244, which may be local diaphragm based sensors connected to a sensor at the proximal end of the device via the multi-lumen catheter, or optical pressure sensors. Alternatively, a single differential pressure sensor may be used that provides a differential pressure reading across the two sensor sites. The size of the inner core 234 may be adjusted based on feedback from the pressure transducers 242, 244, X-ray angiography, or other readings to tailor the performance of the flow characteristics within the vessel. The size of the inner core 234 may also be adjusted without the use of a pressure transducer. As Fig.60B As shown, the balloon 259 can be coupled to the catheter 240 upstream of the flow regulator, for example, a multi-lumen catheter having (multiple) inflation / deflation lumens, so as to increase the IVC resistance without increasing the resistance to flow from the kidney. Thus, the balloon 259 can be selectively inflated / deflated via (multiple) inflation / deflation lumens to achieve the desired IVC resistance, and / or the inner core 234 can be selectively inflated / deflated via (multiple) inflation / deflation lumens. Alternatively, the balloon 259 can be coupled to the catheter 240 downstream of the flow regulator.

[0230] refer to Figures 61A-61B According to another aspect of the present invention, a self-adjusting flexible nozzle is described. In particular, the nozzle may include a flexible membrane 246, such as a stent coated with a polymer, dacron or other elastomeric coating. The flexible membrane 246 in the nozzle area may not follow the contour of the stent 236, and may instead penetrate into the nozzle cavity, creating a free surface 248. The free surface 248 provides a self-adjusting nozzle so that the cross-sectional area of ​​the nozzle can expand in response to IVC flow, such as Fig.61B As depicted. In contrast, when IVC flow is relatively low, the expansion of free surface 248 will be reduced, resulting in a smaller nozzle cross section. In general, when infrarenal IVC flow is relatively low, a smaller sized nozzle is required to produce adequate jetting and local pressure drop. When IVC flow is relatively high (e.g., during exercise), a larger sized nozzle is provided to produce high renal suction. In addition, high IVC flow through a relatively small nozzle may produce an excessively high pressure drop across the ejector, which may result in a significant increase in upstream pressure, or a significant decrease in pressure downstream of the ejector.

[0231] The free surface 248 may include slots that create small fins. Such fins are expected to respond to IVC flow, bending outward when IVC flow is relatively high, and returning inward when IVC flow is relatively low. The fins may be long enough to form a valve so that when the IVC flow is theoretically zero, the fins completely close the nozzle.

[0232] about Figures 62A-62B , describes the effect of the flow regulator on RBF. In general, the flow regulator 10 can be positioned upstream or downstream. In either configuration, an inlet sealing area 250 and an outlet sealing area 252 are formed. Deploying the flow regulator 10 downstream can produce an inlet sealing area 250 just before the renal vein orifice. In contrast, deploying the ejector upstream will produce an outlet sealing area 252, just downstream of the renal vein orifice, thereby achieving better blood flushing in the cavity formed between the flow regulator 10 and the IVC. In this latter configuration, the RBF flows along the outside of the diffuser before entering the opening 226 and merging with the IVC flow. Benefits can also be obtained from deploying a longer flow regulator, where the IVC segment between the common iliac vein and the renal vein can be utilized due to the absence of other major veins. In addition, the flow regulator 10 can be designed so that most of its length is a diffuser, thereby ensuring that the flow of other veins merged into the IVC is not blocked. Only the relatively short inlet sealing area 250 and outlet sealing area 252 can block the flow of the merged vein.

[0233] refer to Fig.63 , depicts a graph of in vitro results of improved simulated RBF using the flow regulator 10 of the present invention. In this experiment, the flow regulator 10 was placed within a simulated silicone IVC model including a renal vein. The IVC flow was set to different flow rate levels. The working fluid was a blood-simulating solution at 37°C with a viscosity of 3.7 cP. For Fig.63 Results shown use an IVC flow rate of 2 L / min. Flow rates out of the renal vein were measured over a range of driving pressures. Fig.63 The RBF measured with a flow regulator placed in a simulated IVC is shown for comparison with a similar experiment without a flow regulator. For example, for a patient with a RBF of 75 ml / min (for a driving pressure of 1.5 mmHg), using the flow regulator of the present invention increases the RBF to about 550 ml / min, which is 7.3 times greater.

[0234] By adjusting the nozzle size, the device of the present invention can provide a wide range of infrarenal IVC flow rates, such as 0.5 L / min (low residual) to 6.0 L / min. For patients with acute decompensated heart failure, the infrarenal IVC flow rate is usually in the range of 0.5-3.0 L / min. Infrarenal IVC flow rate and flow regulator nozzle diameter D nozzleThe ratio range is defined as 0.1-0.75 [L / (min*mm)]. This ratio range covers the combinations of physiological IVC flow rates and nozzle diameters where RBF can be substantially improved without significantly increasing venous pressure. For example, a nozzle size of 5.0 mm and an infrarenal IVC flow of 2.0 L / min yields a ratio of 0.4.

[0235] refer to Figures 64A-64C , describes an inner core used in conjunction with a pump. Any of the designs of the flow regulator 10 and / or inner core 234 described herein can be coupled with a pump 254. The pump 254 can be any pump used to increase flow and / or pressure in a blood vessel and / or heart. Fig.64A and Fig.64B As shown, pump 254 can be coupled to inner core 234 upstream or downstream. Compared with known methods using a restrictor and a pump or two pumps that interact, this configuration results in a smaller pressure loss to reduce pressure in the renal vein area or chest duct drainage area (or any other lymphatic drainage area). There are several advantages to smaller pressure loss. For example, a smaller pump is required and a smaller curling profile can be achieved. For pumps of similar size, a lower RPM is required, thereby reducing thrombosis. In addition, for chronic applications with batteries, smaller batteries can be used. External sources can also be used to increase IVC flow. For example, devices that mimic the natural action of walking calf and / or foot pumps, which are typically used to reduce the risk of deep vein thrombosis by increasing peripheral blood flow, can be used as a power source for any of the designs described herein.

[0236] According to another aspect of the invention, a pump 254, such as an impeller, can be positioned adjacent to the maximum cross-sectional area of ​​the inner core 234, or extend across the entire length of the inner core 234. The pump 254 can rotate with the inner core 234. Preferably, the pump 254 rotates independently of the inner core 234. As described above, when a motor is not required, the pump 254 can be partially rigid and the inner core 234 is an inflatable balloon. Alternatively, both the inner core 234 and the pump 254 can be expandable and curled to the catheter. As described above, the stent can be positioned between the inner core 234 and the inner wall of the blood vessel, thereby preventing damage to the blood vessel by the pump 254.

[0237] Fig.64CThe diagram in shows the difference in pressure loss between the baseline, restrictor + pump design, and the core + pump configuration described herein. In this schematic, the flow rate in each case is the same and the pressure upstream is constant. The baseline represents a constant pressure in the blood vessel. The restrictor + pump line indicates that the pressure is reduced due to resistance, and there is a pump downstream to increase the pressure and maintain a constant flow rate. The pressure loss is represented by ΔP_loss. When the core 234 is used with the pump 254, the flow accelerates and the pressure decreases as the cross-section of the flow area becomes smaller, but the pressure slowly recovers as the cross-section of the flow area increases. The pump 234 then increases the pressure back to the baseline pressure. This pressure loss is represented by ΔP_loss_n.

[0238] Reference now Fig.65 , describes an inner core for use with an external pump and control system. Any of the designs of the flow regulator 10 and / or inner core 234 described herein can be coupled to a pump 255. The pump 255 can be any pump for increasing flow and / or pressure in a blood vessel and / or heart. For example, the pump 255 can be an intermittent pneumatic compression (IPC) or an enhanced external counterpulsation (EECP) pump (such as those provided by ACI Medical, Inc. of San Marcos, California). Device). The pump 255 can be programmed to mimic the natural pumping action of the walking calf and / or foot to move blood in the deep veins of the leg, thereby reducing the formation of deep vein thrombosis. In addition, the pump 255 can provide power to the flow regulator.

[0239] Reference now Fig.66, method steps for adjusting parameters of a flow regulator pump system are provided. For example, a control system with a user interface can be used with a pump 255 and a flow regulator 10 and / or an inner core 234 to adjust the flow through / through the flow regulator 10 and / or the inner core 234. At step 256, the control system can receive pressure measurements from the patient from, for example, the pressure sensors P1, P2, P3 described above, and / or renal / IVC flow rates, and / or conventionally used pressure ports, such as central lines and / or femoral vein sheaths or ports. At step 257, the control system analyzes the renal and / or IVC pressures and / or flow rates based on the received measurements. For example, the measurements can be compared to parameters and thresholds stored in a control system memory. Then, at step 257, based on the analysis from step 257, the control system adjusts the flow rate or aspiration pressure of the flow regulator 10 and / or the inner core 234. For example, the control system can adjust the amplitude and / or frequency of the pump 255, and / or expand / contract any of the inner core 234 or balloon 259 (if used) until the desired flow rate or suction pressure is reached. As will be appreciated by those of ordinary skill in the art, the control system can work with any of the designs of the flow regulator 10 and / or inner core 234 and / or pumps 254 and 255 described herein.

[0240] Although the preferred exemplary embodiments of the present invention have been described above, it will be apparent to those skilled in the art that various changes and modifications may be made therein without departing from the present invention. The appended claims are intended to cover all such changes and modifications that fall within the true spirit and scope of the present invention.

Claims

1. A device for modifying fluid flow through a body cavity, the body cavity being coupled to a branch lumen, the device comprising: A flow conditioner formed by a frame defining a plurality of compartments and configured to be positioned within the body cavity, the flow conditioner comprising an upstream component having an inlet, an outlet, and a cross-sectional flow area converging from the inlet toward the outlet, a downstream component having an inlet, an outlet, and a cross-sectional flow area diverging from the inlet toward the outlet, and an entrainment zone comprising a plurality of longitudinally extending openings radially spaced about the entrainment zone, the entrainment zone being between the inlet of the upstream component and the outlet of the downstream component, wherein the inlet of the downstream component has a diameter greater than the outlet of the upstream component, wherein the framework is at least partially coated with a biocompatible material; wherein an uncoated compartment of said plurality of compartments of said frame defines said plurality of longitudinally extending openings radially spaced about said entrainment region; and wherein the flow conditioner is configured to accelerate a fluid flow passing through the upstream component toward the downstream component to generate a low pressure region proximate the entrainment zone, the entrainment zone entraining additional fluid into the fluid flow via the plurality of longitudinally extending openings as the fluid flow enters the inlet of the downstream component.

2. The apparatus of claim 1, wherein the entrainment zone diverges at the same angle as a divergence angle of at least a portion of the downstream component.

3. The device of claim 1, wherein the entrainment zone is integrally formed with the downstream component.

4. The device of claim 1, further comprising an inner core advanced into at least one of the upstream component or the downstream component.

5. The device of claim 1, wherein the upstream component defines a first plurality of compartments and the downstream component defines a second plurality of compartments, the second plurality of compartments having a structure less flexible than the first plurality of compartments.

6. An apparatus according to claim 5, wherein the downstream component includes a first diverging portion and a second diverging portion, the first diverging portion being upstream of the second diverging portion, and wherein the second diverging portion defines a third plurality of compartments, the average void space area of ​​the first plurality of compartments and the third plurality of compartments being greater than the average void space area of ​​the second plurality of compartments.

7. The device of claim 6, wherein the second plurality of compartments is disposed between the first plurality of compartments and the third plurality of compartments.

8. The device of claim 6, wherein the average void space area of ​​the first plurality of compartments and the average void space area of ​​the third plurality of compartments are substantially the same.

9. The device of claim 1, wherein the downstream component comprises a first diverging portion and a second diverging portion, the first diverging portion being upstream of the second diverging portion, wherein an average diverging angle of the second diverging portion is greater than an average diverging angle of the first diverging portion.

10. The device of claim 1, wherein the upstream component further comprises a narrowing section at an upstream end, the narrowing section configured to allow coupling to a delivery device.

11. The device of claim 10, wherein the narrowed section is configured to remain coupled to the delivery device for acute treatment.

12. The device of claim 1, wherein the downstream component comprises a non-traumatic end.

13. The device of claim 1, wherein the upstream component and the downstream component are at least partially coated with the biocompatible material.

14. The device of claim 6, wherein the first plurality of compartments and the third plurality of compartments are more flexible than the second plurality of compartments.

15. The device of claim 1, wherein the cross-sectional flow area at the outlet of the upstream component is smaller than the cross-sectional flow area at the inlet of the downstream component.

16. The device of claim 1, wherein the upstream component, the downstream component, and the entrainment zone comprise a single frame coated with one or more biocompatible materials.

17. The device of claim 1, wherein the length of the downstream component is greater than the length of the upstream component.

18. The apparatus of claim 1, wherein the average convergence angle of the upstream component is greater than the average divergence angle of the downstream component.

19. The apparatus of claim 1, wherein the upstream component comprises a nozzle that accelerates the fluid flow through the upstream component, and the downstream component comprises a diffuser that decelerates the fluid flow with the entrained additional fluid through the downstream component.

20. The device of claim 4, wherein the inner core has an upstream region and a downstream region, the upstream region including a first end and a cross-sectional area that increases from the first end toward the downstream region, the downstream region including a second end and a cross-sectional area that decreases from the upstream region toward the second end, and The inner core is configured to accelerate a fluid flow passing between the inner core and the branch lumens around the upstream region toward the downstream region.

21. The device of claim 20, wherein the inner core comprises a balloon.

22. The device of claim 20, wherein the downstream region extends through an entire section where the body lumen intersects the branch lumen.

23. The device of claim 20, wherein the region of the core having the largest cross-sectional area is positioned upstream of the branch lumen.

24. The device of claim 20, wherein the inner core is symmetrical about a longitudinal plane extending along a longitudinal axis of the inner core.

25. The device of claim 24, wherein a diameter or thickness of the inner core varies continuously from the first end of the upstream region to the second end of the downstream region.

26. The device of claim 20, wherein the inner core is completely suspended within the body cavity without contacting the inner wall of the body cavity.

27. The device of claim 20, wherein a rate at which the cross-sectional area of ​​the upstream region increases from the first end toward the downstream region is greater than a rate at which the cross-sectional area of ​​the downstream region decreases from the upstream region toward the second end.

28. The device of claim 20, wherein the fluid flow passes only around the upstream region between the inner core and the branch lumens toward the downstream region and does not pass through the inner core.

29. The device of claim 20, further comprising a stent configured to secure the inner core within the body cavity.

30. The device of claim 20, further comprising a guide wire, the inner core being attached to the guide wire.

31. The apparatus of claim 20, further comprising a pump configured to be coupled to at least one of the upstream region or the downstream region.

32. A delivery device for delivering the flow regulator according to claim 1, the delivery device comprising: a sheath having an inner lumen sized to retain the flow regulator therein in a retracted delivery state during delivery; as well as An inner assembly is slidably disposed within the lumen of the sheath to facilitate deployment from the distal end of the sheath.

33. A device for modifying fluid flow through a body cavity coupled to a branch lumen, the device comprising: A flow conditioner formed by a frame defining a plurality of compartments and configured to be positioned within the body cavity, the flow conditioner comprising an upstream component and a downstream component defining a gap, the upstream component having an inlet, an outlet, and a cross-sectional flow area converging from the inlet toward the outlet, the upstream component defining a first plurality of compartments of the plurality of compartments, the downstream component having an inlet, an outlet, and a cross-sectional flow area diverging from the inlet toward the outlet, the downstream component defining a second plurality of compartments of the plurality of compartments, the second plurality of compartments being less flexible in structure than the first plurality of compartments, wherein the gap defines a path communicating with the branch lumen, the gap being disposed between the inlet of the upstream component and the outlet of the downstream component, wherein the diameter of the inlet of the downstream component is greater than the diameter of the outlet of the upstream component, wherein the frame is at least partially coated with a biocompatible material, wherein an uncoated compartment of the plurality of compartments of the frame defines the gap; and The flow conditioner is configured to accelerate a fluid flow passing through the upstream component toward the downstream component to generate a low pressure region near the gap and to entrain additional fluid into the fluid flow as the fluid flow enters the inlet of the downstream component.

34. The apparatus of claim 33, wherein the downstream component comprises a first diverging portion and a second diverging portion, the first diverging portion being upstream of the second diverging portion.

35. The device of claim 34, wherein the average divergence angle of the second divergent portion is greater than the average divergence angle of the first divergent portion.

36. The device of claim 34, wherein the second diverging portion defines a third plurality of compartments among the plurality of compartments, the third plurality of compartments being more flexible in structure than the second plurality of compartments.

37. The device of claim 36, wherein the second plurality of compartments is disposed between the first plurality of compartments and the third plurality of compartments.

38. The device of claim 36, wherein the first plurality of compartments and the third plurality of compartments have substantially the same flexibility.

39. The device of claim 36, wherein the average void space area of ​​the first plurality of compartments and the third plurality of compartments is greater than the average void space area of ​​the second plurality of compartments.

40. The device of claim 36, wherein the first plurality of compartments and the third plurality of compartments have a diamond shape, and the second plurality of compartments have a hexagonal shape.

41. The device of claim 40, wherein the average void space area of ​​the second plurality of compartments is greater than the average void space area of ​​the first plurality of compartments and the third plurality of compartments.

42. The device of claim 33, wherein the average void space area of ​​the second plurality of compartments is less than the average void space area of ​​the first plurality of compartments.

43. The device of claim 33, wherein the upstream component further comprises a narrowing section at an upstream end, the narrowing section configured to allow coupling to a delivery device.

44. The device of claim 43, wherein the narrowed section is configured to remain coupled to the delivery device for acute treatment.

45. The device of claim 33, wherein the downstream component comprises a non-traumatic end.

46. ​​The device of claim 33, wherein the upstream component and the downstream component are at least partially coated with a biocompatible material.

47. The apparatus of claim 33, wherein the cross-sectional flow area at the outlet of the upstream component is smaller than the cross-sectional flow area at the inlet of the downstream component.

48. The device of claim 33, wherein the upstream component and the downstream component are formed from a single frame.

49. The device of claim 33, wherein the length of the downstream component is greater than the length of the upstream component.

50. The apparatus of claim 33, wherein the average convergence angle of the upstream component is greater than the average divergence angle of the downstream component.

51. The apparatus of claim 33, wherein the upstream component comprises a nozzle that accelerates the fluid flow through the upstream component, and the downstream component comprises a diffuser that decelerates the fluid flow with the entrained additional fluid through the downstream component.

52. A delivery device for delivering the flow conditioner according to claim 33, the delivery device comprising: a sheath having an inner lumen sized to retain the flow regulator therein in a retracted delivery state during delivery; as well as An inner assembly is slidably disposed within the lumen of the sheath to facilitate deployment from the distal end of the sheath.

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