Perfusion systems and methods for monitoring tissue oxygenation and reducing limb ischemia

Abstract

Perfusion systems and methods for increasing peripheral blood flow to reduce limb ischemia are provided in which an extracorporeal pump and catheter / conduit set with a controller, used alone or in combination with an interventional or circulatory assist device, draws blood from the vasculature of a patient, and reintroduces the blood into another location within the patient's vasculature at a controllable local pressure or flow rate without interfering with the operation of an interventional or circulatory assist device or surgical intervention.

Description

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS

[0002] This disclosure claims the benefit of priority to U.S. Provisional Patent Application Serial No. 63 / 362,363, filed on April 1, 2022, the contents of which are incorporated by reference in their entirety. Technical Field

[0003] The present invention generally relates to systems and methods for monitoring tissue oxygenation and reducing ischemia by providing enhanced perfusion to a patient's extremities. In particular, the systems and methods of the present invention can be used to treat any condition that induces limb ischemia, including thrombotic or thromboembolic vascular occlusions, or during medical procedures involving the use of devices that obstruct blood flow in a vessel (e.g., cardiac or vascular surgery, coronary or cardiac catheterization, insertion of a cardiac support device and / or subsequent management of peripheral arterial disease and / or surgical or interventional procedures requiring a tourniquet), or other causes of acute limb ischemia, shock or trauma patients, or patients with existing peripheral arterial disease. Background Art

[0004] Decreased blood flow and / or blood pressure in a patient's extremities, such as the legs and arms, may result from any of a number of causes, leading to acute or chronic ischemia of the extremities. During an interventional procedure, such as a percutaneous cardiac intervention, such as stent placement, heart valve repair, or coronary or cardiac catheterization, a catheter may be placed in the patient's vasculature that occludes flow in their blood vessels. Similarly, placement of a circulatory support device, such as a percutaneous ventricular assist device (pVAD), an intra-aortic balloon pump (IABP), or a cannula for an extracorporeal membrane oxygenation system (ECMO), in a blood vessel may occlude downstream flow near the entry point of the circulatory support device.

[0005] Shock caused by cardiogenic shock, such as myocardial infarction, myocarditis, pulmonary embolism, venous occlusion, heart valve or myocardial rupture, and many other disease states can also lead to decreased blood flow to the extremities, many of which manifest as the patient's heart being unable to pump enough oxygenated blood to the body's organs. Decreased blood circulation due to cardiogenic shock can lead to chronic ischemia of the patient's extremities, which may require amputation. Decreased peripheral blood circulation can also be caused by the presence of peripheral artery disease and as a side effect of peripheral vascular interventions.

[0006] In addition, limb ischemia may also result from the use of medical tourniquets, which are often used in cases of vascular trauma or during procedures such as knee surgery to reduce bleeding in the surgical interface. Tourniquets reduce arterial and venous blood flow and may cause limb ischemia if used for a long time. In these cases, the present invention can use two bypass circuits to allow arterial and venous blood flow, respectively, thereby maintaining limb perfusion while the tourniquet is used.

[0007] One approach to increasing blood flow to the limbs of patients with poor peripheral circulation due to occlusion caused by placement of an interventional device (e.g., a catheter shaft or cannula) or circulatory assist device (pVAD or IABP) in the iliac, femoral, or axillary arteries is to create an extracorporeal shunt using tubing from a location upstream of the occlusion to a cannula inserted into the patient's arterial system at a distal location downstream of the occlusion. U.S. Pat. No. 9,782,279 to Kassab is an example of such a passive perfusion system. However, it has been observed that this proposed solution is ineffective in reducing limb ischemia, requires temporary placement, and is associated with a high incidence of adverse outcomes, including prolonged hospital stays, limb amputations, and increased mortality.

[0008] Furthermore, in addition to limb ischemia, medical complications may arise because the rapid and catastrophic accumulation of blood in the pericardium impedes cardiac function, thereby reducing systemic circulation. One method of reducing hemopericardium is to manually and repeatedly aspirate the blood from the pericardium. This process continues until the patient is taken to the operating room, which may take one to four hours.

[0009] In view of the foregoing, it is desirable to provide systems and methods for monitoring tissue oxygenation and / or increasing blood pressure and blood flow in the extremities of a patient undergoing an interventional procedure or using a circulatory assist device, wherein an interventional device, circulatory assist device, tourniquet, or other natural cause (i.e., thrombosis) has caused an occlusion in any artery or vein (i.e., iliac, femoral, axillary, brachial artery, or vein) and which overcome the shortcomings of previously known solutions. In particular, it is desirable to provide devices and methods for enhancing blood flow and maintaining blood pressure in the peripheral vasculature to adequately salvage a limb.

[0010] It would be further desirable to provide devices and methods for enhancing peripheral blood flow that reduce blood stagnation, particularly near the catheter or cannula insertion site, thereby reducing the risk of thrombosis.

[0011] It would be further desirable to provide apparatus and methods for increasing peripheral blood flow in patients undergoing vascular intervention or other surgical procedures involving the use of a tourniquet, as well as patients recovering from peripheral vascular intervention, which are intended to reduce the risk of blood leakage at the device insertion site. Summary of the invention

[0012] The present invention relates to systems and methods for monitoring tissue oxygenation, vascular or local pressure, and / or increasing peripheral blood flow and vascular pressure to reduce limb ischemia in patients with arterial or venous occlusion due to disease symptoms or due to cardiac or vascular interventional treatment, wherein the interventional device or tourniquet causes at least partial occlusion of downstream blood flow. According to the principles of the present invention, the device of the present invention includes an extracorporeal pump and a cannula / tubing set, which can be used alone or in combination with any surgery or device that blocks blood flow to extract oxygenated blood from the patient's vascular system or anatomical cavity (i.e., pericardium) and reintroduce the blood at another location in the patient's vascular system at an independently controlled vascular system pressure or flow rate. In this way, the blood flow rate or blood pressure in the patient's limbs can be independently controlled without interfering with the placement or operation of the interventional device or circulatory assist device. In a preferred embodiment, the flow rate can be adjusted to achieve a target vascular pressure, thereby increasing the oxygenation of tissues in the limbs that are ischemic or at risk of ischemia. The output of a near infrared spectroscopy (NIRS) sensor or other oxygen sensing device applied to the affected limb can also be used as an input to the device of the present invention to adjust the perfusion flow or pressure. Inlet suction pressure can also be used as a determining factor for bypass flow.

[0013] In a preferred embodiment, the system of the present invention includes an inlet cannula, which is configured to be placed in an artery or vein of the patient, and includes a central lumen through which an interventional vascular device or a circulatory assist device can be inserted. The inlet cannula may include a hemostatic valve and a side port, and blood enters the inlet of an extracorporeal pump from the inlet cannula through the side port. The extracorporeal pump then pushes blood back to the patient's vascular system with a selected pressure or flow rate through a return lumen with an outlet downstream of the inlet cannula. In one embodiment, the outlet of the return lumen is embodied in a separate return cannula. In this embodiment, a pressure sensor can be placed near its outlet end in the return conduit for measuring the pressure in the blood vessel, and the output of the pump can be automatically adjusted to maintain the desired pressure in the blood vessel. In addition, the output of a NIRS sensor or other oxygen sensing device for monitoring tissue oxygenation can be additionally used to provide input for a feedback loop controlling pump performance.

[0014] In an optional embodiment, the inlet cannula and the return lumen can be embodied in a single cannula. In one such embodiment, the return lumen is a second lumen of the inlet cannula, and is open to a slit in the side surface of the inlet cannula, so that the blood flowing out of the extracorporeal pump flows back into the vascular system downstream of the inlet of the inlet cannula. An occlusion balloon can be placed near the distal end of the inlet cannula to partially or completely occlude the antegrade blood flow through the artery, so that the blood is instead guided to the extracorporeal pump, and the blood returned from the pump does not flow in the retrograde direction. In this way, the blood flowing back from the extracorporeal pump to the patient is transported in the retrograde direction below the occlusion balloon to perfuse the patient's peripheral vascular system. The extracorporeal pump and / or cannula may include a pressure and flow sensor for monitoring the inlet and outlet pressures and blood flow velocity, and the extracorporeal pump may include a controller for determining and maintaining a blood flow velocity or pressure specified by a doctor or automatically determined in the perfused blood vessel. The inlet cannula may also include a balloon separated from the occlusion balloon for sealing the cannula insertion site to prevent leakage.

[0015] According to another aspect of the invention, the occlusion balloon may be configured to have a concave profile on its proximal face to direct blood flow from the reflux lumen incision to flow in a retrograde direction. Alternatively, or in addition, the distal face of the occlusion balloon may be funnel-shaped when filled to reduce the formation of blood stagnation areas. Still further optionally, the occlusion balloon itself may be perforated so that blood introduced into the balloon can both expand the balloon to contact the vessel wall to provide partial or complete occlusion and pass through the perforations to provide retrograde blood flow to the patient's extremities.

[0016] In yet another embodiment, the perfusion system may include an inlet catheter inserted into the iliac artery, femoral artery, or axillary artery or vein, and a return catheter of smaller diameter inserted through the lumen of the inlet catheter. An extracorporeal pump is configured to draw blood through the annular cavity formed between the inside of the inlet catheter and the outside of the return catheter. The extracorporeal pump delivers blood through the return catheter and delivers the blood back to the vascular system at a downstream position closer to the limbs at a controllable pressure or flow rate. In yet further embodiments, the perfusion system may include multiple inlet cannulas to extract blood from the arterial and venous vascular systems, and multiple return catheters to provide enhanced perfusion for multiple limbs. In addition, multiple pumps or pump heads may be used, which may be independently controlled based on oxygenation, pressure, or flow input from a specific area of ​​desired perfusion.

[0017] The extracorporeal pump suitable for the perfusion system of the present invention may include any suitable commercially available blood pump design, including vane pumps, centrifugal pumps, diaphragm pumps, piston pumps, and roller pumps. In one embodiment, the extracorporeal pump may be capable of producing a pulsatile flow. In another embodiment, the extracorporeal pump may be capable of producing a non-pulsatile flow.

[0018] Other features of the present systems and methods will become apparent from the following description and drawings. BRIEF DESCRIPTION OF THE DRAWINGS

[0019] Figure 1 is a schematic diagram of a perfusion system constructed according to the principles of the present invention, wherein an extracorporeal pump is connected between an inlet catheter and a return catheter, and an interventional or circulatory assist device can be placed through the inlet catheter.

[0020] Figure 2A and Figure 2B Schematic diagram of an optional embodiment of the perfusion system of the present invention and a cross section of a double-lumen catheter, wherein Figure 1 The features of the inlet catheter and return catheter of an embodiment are integrated into a double lumen catheter.

[0021] Figure 3A and Figure 3B 2, but further comprising an occluding balloon for partially or completely occluding anterograde flow through the blood vessel and a sealing balloon for preventing excessive blood loss through the opening of the perfusion cannula into the blood vessel.

[0022] Figure 4A and Figure 4B 2 are a side view of an embodiment in which the inlet catheter includes a recessed occlusion balloon to direct reperfused blood, and a side view of another alternative embodiment in which a perforated material is placed over the cutout in the flashback lumen to more evenly distribute the blood reperfused into the vessel.

[0023] Figure 5A and Figure 5B 3 is replaced by a balloon having a distal portion for occluding downstream flow and a perforated proximal portion through which blood returns to the blood vessel; in this optional embodiment, the distal and proximal surfaces of the balloon are inclined relative to the axis of the cannula to form a distal funnel and an enlarged proximal area for dispersing blood delivered by the extracorporeal pump.

[0024] Figure 6 4 , wherein the occlusion balloon is inflated with blood delivered by an extracorporeal pump to partially or completely occlude antegrade flow, while the perforated proximal surface of the balloon disperses the blood delivered by the extracorporeal pump to provide antegrade flow with controlled volume and pressure.

[0025] Figure 7 is a schematic diagram of a perfusion system of the present invention, wherein coaxial inlet and return conduits are connected to an extracorporeal pump.

[0026] Figure 8is an exemplary roller pump for providing pulsed flow suitable for use with the perfusion system of the present invention.

[0027] Fig. 9A , Fig. 9B and Fig. 9C is a schematic diagram of the operation of a piston pump for generating a pulsed flow, which is suitable for the perfusion system of the present invention.

[0028] Fig. 10A and Fig. 10B Schematic block diagrams of an extracorporeal pump and software, respectively, for use in an exemplary controller for controlling the operation of an extracorporeal pump used in the perfusion system of the present invention.

[0029] Fig.11 is a screenshot of a display showing the results of near infrared spectroscopy monitoring of limb oxygenation in an animal experiment, where the animal's left limb was perfused by an embodiment of the present invention and the right limb was passively perfused.

[0030] Fig. 12A and Fig. 12B is a graph depicting tissue oxygenation and arterial blood gas values ​​from different animal studies, showing the difference between active and passive perfusion.

[0031] Fig.13 yes Figure 1 Another optional embodiment of the perfusion system, wherein the extracorporeal pump is supplied with blood by two inlet cannulas and returns blood through a return cannula. DETAILED DESCRIPTION

[0032] The present invention relates to a perfusion system for monitoring tissue oxygenation and / or enhancing perfusion of a limb of a patient who has reduced blood flow to a limb due to any of a number of reasons. The cause of such reduced blood flow may include the placement of a percutaneous interventional device or circulatory assist device in an artery or vein that results in partial or complete occlusion of downstream blood flow in that vessel, or as a sequela of cardiogenic shock or peripheral arterial disease, or as a result of any surgery that requires the use of a tourniquet or other method to block blood flow to a certain area. In accordance with the principles of the present invention, a perfusion system draws arterial blood from a location upstream of the occlusion or reduced blood flow area and delivers the blood back to the vessel or to an adjacent or contralateral vessel at a controlled vascular pressure or flow rate volume, thereby reducing the risk of limb ischemia. In addition, the blood flow to the limb through the pump can be regulated by physiological feedback (such as tissue oxygen content).

[0033] It is hypothesized that acute and / or chronic limb ischemia that occurs in patients during vascular interventions is due to partial or complete obstruction of arterial or venous blood flow downstream due to blood clots, trauma, tourniquets, or the presence of catheters or circulatory assist devices in interventional devices. Other potential causes may include impaired cardiac output, arteriosclerosis, and / or a general increase in vascular hydraulic resistance in the limbs, all of which may result in reduced blood flow to the limbs when local pressures are low. Reduced peripheral blood flow and / or blood pressure, in turn, may result in increased thrombosis, worsening limb ischemia, and an increased risk of myocardial infarction, pulmonary embolism, and stroke. Therefore, to address these issues, the systems and methods of the present invention are intended to direct a portion of the blood flow to the limbs to an extracorporeal blood pump, which returns the blood flow to the same or another vessel at a controlled pressure or flow rate sufficient to reduce ischemia.

[0034] Other patient-experienced complications of interventional procedures, such as coronary artery perforation, cardiac rupture, right heart free wall perforation from biopsy, or aortic or other valve rupture during valve replacement, can result in rapid and catastrophic accumulation of blood within the pericardium, thereby impeding the function of the native heart. As excess blood is drained from the pericardium, the patient may require a blood transfusion to replace the aspirated blood. The systems and methods of the present invention are further intended to direct a portion of the accumulated blood into an extracorporeal blood pump, which returns the blood to the systemic circulation.

[0035] As described in the background, some surgeons and interventional clinicians have attempted to increase blood flow to a patient's extremities by passively diverting blood from areas of higher pressure / flow (e.g., arteries close to the heart) to remote arterial locations (e.g., the femoral artery) using tubing sets. Such attempts have been unsatisfactory due to a number of factors, including the inherently low flow rates and pressures of such passive systems, as well as the hydraulic resistance encountered in the tubing sets. Applicants believe that the presence of low pressure in the vasculature of the extremities may result in insufficient oxygen absorption in the capillaries, even in the presence of substantial blood flow. Applicants have the insight that by providing an extracorporeal blood pump, the blood flow rate and vasculature pressure supplied to the patient's extremities may be better controlled, thereby perfusing the extremities and reducing the risk of ischemia. In addition, providing one or more separate extracorporeal blood pumps allows for independent control of perfusion of the extremities without being affected by the operation of any vascular device or circulatory assist device that may cause an occlusion. The systems and methods of the present invention further enable clinicians to monitor perfusion of the patient's extremities and adjust flow in real time to achieve a target pressure in the perfused vessels. It should be understood that when describing various embodiments, the terms "vessel pressure", "vascular pressure", "local pressure", "blood pressure" or some combination of these terms refer to the fluid pressure within the patient's blood vessels and / or capillaries.

[0036] Now refer to Figure 1 , describes an exemplary perfusion system 10 arranged according to the principles of the present invention. The system 10 includes an inlet cannula 12, a return cannula 14, and an extracorporeal pump 16 connected by a conduit 18. The inlet cannula 12 is configured to be placed in a femoral artery, an iliac artery, or an axillary artery or vein, and includes a proximal end 20 having an outlet port 22 and a hemostasis port 24, through which an interventional device or a circulatory assist device can be inserted to perform an interventional procedure or assist cardiac function. The distal end 28 of the inlet cannula 12 is configured to be placed in an antegrade direction in a blood vessel to assist in positioning the interventional device or circulatory assist device. The inlet cannula 12 has a sufficiently large diameter, such as 16-22 Fr, and its annular cavity 30 is formed by the outer surface of the device inserted therein and the inner surface of the inlet cannula 12, so that blood flow will flow to the outlet port 22 and enter the inlet 32 ​​of the pump 16.

[0037] In an alternative or additional option, the inlet cannula can be a pigtail catheter that is inserted into the pericardium when hemopericardium accumulates. The accumulated blood then drains from the pericardium and automatically perfuses into the vascular sheath through the return lumen. Such an embodiment can achieve two life-saving treatments: 1) draining the pericardium so blood does not accumulate and impede heart function; and 2) automatically transfusing blood to the patient so they do not require excessive blood products.

[0038] In one embodiment, the return cannula 14 can be configured to be placed in the iliac artery, femoral artery or axillary artery or vein of the patient, with the outlet end 34 facing the retrograde direction. In this direction, the blood delivered from the outlet 36 of the pump 16 through the lumen 38 of the return cannula 14 is directed toward the inlet cannula 12 to flush any stagnant area generated when the inlet cannula 12 enters the blood vessel. The return cannula 14 may also include a valve 40 at its proximal end. In this way, at least part of the blood flowing out of the outlet end 34 of the return cannula 14 first flows in the retrograde direction and then flows to the patient's limbs in the antegrade direction. The return cannula 14 may also have a perfusion port to allow the pump circuit to be used for blood transfusion at the same time, and / or one or more delivery ports for delivering a reperfusion protective agent or therapeutic agent to reduce or eliminate reperfusion injury. Such reperfusion protective agents or therapeutic agents may include, but are not limited to, anticoagulants and thrombolytic agents.

[0039] In alternative embodiments, the return cannula may be configured to be placed at a more distal location in the peripheral circulation, spaced from the insertion site of the occlusion sheath. For example, the return cannula may be placed in a vein or artery near the ankle joint when treating leg ischemia, or in a vein or artery near the wrist joint when treating arm ischemia, even though the ankle or wrist joint is not near the occlusion.

[0040] The extracorporeal pump 16 with display panel 17 can be a conventional, commercially available blood pump capable of continuous or pulsed flow, using any known pumping technology, such as a vane pump, diaphragm pump, gear pump, roller pump, centrifugal pump, axial flow pump, balloon mounted pump or piston pump. In a preferred embodiment, the extracorporeal pump 16 is driven by a motor and includes a controller that allows adjustment of vascular pressure or flow rate. The display panel 17 can be a touch screen device that can adjust the operation of the pump and display the output of a sensor placed on the cannula. According to one aspect of the present invention, the extracorporeal pump 16 can include or communicate with a pressure sensor that senses the blood pressure at the distal end 28 of the inlet cannula 12 and the outlet end 34 of the return cannula 14, as well as measures the flow rate through the pump and senses whether there is an obstruction. In this embodiment where the pump controller communicates with a pressure sensor located in a limb vein or artery, it is desirable to have the pressure sensor measure local blood pressure through a lumen separate from any inlet or return lumen, such as the lumen described in Figures 2 and 3 below. The use of a separate lumen allows the transmission or measurement of local pressure to be unaffected by the flowing blood. It will be appreciated by those skilled in the art that pressure sensors may also be located at the inlet port 32 and the outlet port 36. However, in such an embodiment where the pressure sensors are placed at the inlet and outlet ports, it is desirable to account for the pressure drop caused by friction in the pump circuit. This pressure drop may be accounted for by using a target pressure higher than the ideal target vascular pressure, reducing friction in the pump circuit, or a combination of both. For example, to reduce friction in the pump circuit, it may be desirable to coat the inner surface of the cannula with a layer of polytetrafluoroethylene, such as Teflon®. TM .

[0041] Further according to the present invention, the controller may include a processor that is programmed to sense the vascular resistance of the outlet port 36. The controller may be further automatically programmed to adjust the outlet pressure and flow rate to maximize limb perfusion while avoiding the use of excessive pressure, which may cause extravascular leakage and edema. In addition, the extracorporeal pump 16 may be configured to generate a pulsed flow at the outlet 34 of the return cannula 14, which simulates the pressure fluctuations of the normal cardiac cycle, thereby reducing the risk of thrombosis. As a further option, the pump may be synchronized with the ECG output or pressure wave sensor to eject blood during diastole, thereby reducing the afterload of the heart. In a further addition, the pump may be configured to oxygenate the blood flowing through the pump when the vascular pressure or flow rate is increased or insufficient. Those of ordinary skill in the art will recognize the possibility of connecting a separate extracorporeal membrane oxygenation system (ECMO) to the pump circuit. In an optional option, an inlet cannula can provide arterial blood for the pump, and venous blood and / or transfusion can be input through ECMO before the input pump. Then, the pump supplies this combination of arterial blood and oxygenated venous blood and / or transfusion through the return lumen.

[0042] According to another aspect of the present invention, the extracorporeal pump may be configured to maintain perfusion pressure rather than a selected output flow rate. For example, the extracorporeal pump may deliver blood so as to maintain the average perfusion pressure of a limb, such as a leg or an arm, by constantly changing the flow rate. In addition, the blood supply delivered to the pump may come from other parts of the body, such as an arm or other leg, rather than just the upstream of the blood vessel of the reperfused blood. In addition, the controller of the pump may communicate with sensors that measure the oxygen content of the blood and / or tissue in the reperfused limb. Such sensors may use various measurement standards, such as measuring blood oxygen saturation (SpO2), arterial blood gas (PaO2), near infrared spectroscopy (NIRS) levels to measure absolute tissue saturation (StO2), pH or lactate levels. For example, the return cannula 14 may include an integrated NIRS sensor 35 near its distal end for measuring the tissue oxygenation level of the tissue surrounding the cannula at the reperfusion site. An example of an integrated NIRS sensor suitable for such use is described in an article published by KD Akkel et al. entitled "Integrated near-infrared spectral sensing", Nature Communications, 13:103 (2022), available at https: / / doi.org / 10.1038 / s41467-021-27662-1. In this case, a controller of the extracorporeal pump can provide readings of flow rate, local blood pressure in the perfused vessel, and tissue oxygenation level on display 17. The controller can also be programmed, such as via display panel 17, to allow an operator to select a combination of cycle length and outflow pressure that provides the highest flow at the target vessel pressure to achieve or maintain the target tissue oxygenation level.

[0043] Preferably, the controller of the extracorporeal pump has multiple modes of operation. In each mode of operation, the feedback loop controlling the pump is based on different measured variables. In flow mode, the operator will manually set the flow rate at which the pump perfuses the limb. In vascular or local pressure control mode, the system will perfuse the leg at a specific vascular pressure, and this target pressure will be determined manually or automatically. Similarly, in tissue oxygen control mode, the system will perfuse the limb to achieve a specific tissue oxygen level, and this target oxygen level will be determined manually or automatically. In any of these modes, the measured variables can be manually entered or automatically determined by an artificial intelligence component. The software of the controller can also include an artificial intelligence component that prompts the controller to re-evaluate the selected combination at different time intervals to optimize the settings that are most suitable for a particular patient. Optionally, the pump circuit can act as a passive bypass circuit until the controller detects, via sensor 35, a drop in tissue oxygenation levels that may cause limb ischemia. Once the controller detects that the tissue oxygenation level drops below a predetermined value, the controller can automatically start the pump.

[0044] According to another aspect of the present invention, the pump may have two or more return cannulas, each of which supplies blood to different limbs, each of which supplies blood to different regions or veins / arteries of the same limb, or each of which supplies blood to different regions of multiple limbs, such as supplying blood to the upper and lower parts of the legs at the same time, and supplying blood to the arms near the shoulders and near the wrists. In this embodiment, it is desirable to maintain a constant flow rate or constant vascular pressure for some or all of the limbs that are reperfused. Otherwise, it may be necessary to use a pressure control valve or a flow rate control valve to change the flow rate or pressure of one limb without changing the flow rate or pressure of another limb. The inlet cannula is optionally connected to multiple pumps or a single pump with multiple stages so that each pump or stage is used to reperfuse different limbs. In this embodiment, each limb can maintain its own flow rate or vascular pressure. As another option, there can be multiple inlet cannulas, which supply blood to the same or different pumps or motors, respectively. In this embodiment, it is desirable that each inlet cannula is inserted into a different vein or artery or transfusion supply. The blood reperfusion system may use any combination of multiple return cannulas and inlet cannulas and single or multiple pumps or motors. These inlet cannulas can then supply blood to the same pump, two different pumps, or one or both inlet cannulas can supply blood to more than one pump. When both inlet cannulas supply blood to the same pump, the pump may have one or more return cannulas. When the inlet cannulas supply blood to multiple pumps, each pump may have one or more return cannulas. When there is more than one return cannula, each return cannula may supply blood to a different limb, different areas of the same limb, different veins and / or arteries of the same limb, or some combination of the above.

[0045] For example, refer to Fig.13, the pump 376 may have two inlet cannulas and one return cannula. The first inlet cannula may be an arterial inlet cannula 318 inserted into a limb artery 332, and the second inlet cannula of the pump 376 is an oxygenated inlet cannula 316 that delivers oxygenated blood from the ECMO 320. The ECMO 320 may be supplied by a venous inlet cannula 314 and an infusion cannula 312, wherein the infusion cannula supplies the ECMO with infused blood 310. The blood supplied to the pump 376 by the arterial inlet cannula 318 and the oxygenated inlet cannula 316 is then mixed before returning to the vein or artery 334 through the return cannula 322. A person of ordinary skill in the art will appreciate that there are many other possible combinations. For example, the pump may have three inlets. One inlet is for transfusion, one inlet is for venous blood, and one inlet is for arterial blood. In this embodiment, the ECMO may be omitted, or only one of the transfusion, venous blood, or arterial blood may be oxygenated. The pump may also have more than one return cannula, each of which returns blood to different areas or different limbs of a limb. In this embodiment, the pump may or may not mix the inlet blood before supplying it to the return cannula. As a further option, the reperfusion system may have more than one pump or motor. For example, each inlet and / or each return may have a single pump or motor. In another example, a single pump or motor may be used for the venous inlet cannula and a single pump or motor may be used for all arterial inlet cannulas.

[0046] According to another aspect of the invention, the device can be used to provide flow to one or more vascular compartments. For example, using a single motor and a single console or independent motors and consoles, two rotors can be used to bypass two arteries or one artery and one vein or two veins. This application is particularly useful when a complete blockage of blood flow to and from a limb occurs or is required, such as in the case of a tourniquet. In this case, the device will provide antegrade arterial blood flow to the limb and retrograde venous blood flow out of the leg. This will achieve optimal limb perfusion. In another example, a multi-rotor device can provide arterial bypass for both legs or a leg and an arm at the same time.

[0047] Watch now Figure 2A and Figure 2B , which describes an alternative embodiment of a perfusion system constructed according to the principles of the present invention. The perfusion system 50 is designed to provide Figure 1 The system 10 of FIG. 1 has similar functions, but uses a double lumen cannula 52 instead of separate inlet and return cannulas. The cannula 52 includes a distal end 54 having an inlet 55, a proximal end 56 having a valved inlet port 58 and an outlet port 60, and a hemostatic valve 62 through which an interventional or circulatory assist device 64 can be inserted. Figure 2BAs depicted, cannula 52 has an inlet lumen 66 and an outlet lumen 68, which opens to an incision 70 at a proximal position of distal end 54. A NIRS sensor 69 may be located downstream of incision 70 to sense tissue oxygenation in the reperfused area. Inlet lumen 66 is large enough so that an annulus 72 is formed around axis 74 of device 64 so that an extracorporeal pump 76 can draw blood from a blood vessel through inlet 55 of distal end 54, annulus 72, and inlet port 58. Extracorporeal pump 76 is connected to inlet port 58 and outlet port 60 of cannula 52 by tubing 78 so that blood flowing out of pump 76 passes through outlet port 60, lumen 68, and incision 70. Pump 76 may include a built-in display panel 77, which is both an input device and a display screen.

[0048] The extracorporeal pump 76 may be Figure 1 , and preferably includes pressure and flow sensors for monitoring flow characteristics, such as local blood pressure and flow rate, at the distal ends of the inlet and return cannulas. In addition, pump 76 can be configured to provide pulsed flow to incision 70 to perfuse the limb at a controlled pressure or flow rate. Although incision 70 is opposite to the vessel wall, it is expected that the blood flow through lumen 68 is sufficient to locally move cannula 52 away from the vessel wall, thereby allowing blood to flow freely in the antegrade direction.

[0049] Reference now Figure 3A and 3B , describes a further alternative embodiment of the perfusion system of the present invention. System 80 includes a multi-lumen cannula 82 connected to an extracorporeal pump 84 via a conduit 86. An extracorporeal pump 84 suitable for use with cannula 82 may have Figure 1 and any features of the embodiment described in the perfusion system of FIG. 2. The cannula 82 is similar in design to Figure 2A and 2B The cannula 52 of the embodiment is described above, except that it further includes an occluding balloon and an optional sealing balloon.

[0050] More specifically, cannula 82 includes a distal end 88 having an inlet port 89, a proximal end 90 having a valved inlet port 92 and an outlet port 94, balloon filling ports 96 and 98, and a hemostatic valve 100 through which an interventional or circulatory assist device 102 may be inserted. Figure 3BAs shown, the cannula 82 has an inlet lumen 104, balloon filling lumens 106 and 108, and an outlet lumen 110, which opens to a cutout 112 at a proximal position of the distal end 88. The inlet lumen 104 is large enough to form an annular cavity 114 around the axis 116 of the device 102, so that the extracorporeal pump 84 can draw blood from the blood vessel through the inlet 89 of the distal end 88, the annular cavity 114, and the inlet port 110. The extracorporeal pump 84 is connected to the inlet port 92 and the outlet port 94 of the cannula 82 through the tubing 86, so that the blood flowing out of the pump 84 will flow through the outlet port 94, the lumen 110, and the cutout 112.

[0051] Still refer to Figure 3A and Figure 3B The cannula 82 further includes an occluding balloon 118 and an optional elongated sealing balloon 120, the occluding balloon 118 being placed between the distal end 88 and the incision 112 to partially or completely block antegrade blood flow through the blood vessel, and the sealing balloon 120 being placed proximal to the incision 112 to reduce blood leakage around the cannula 82 when entering the blood vessel. The occluding balloon 118 maintains fluid communication with the filling port 96 through the filling lumen 106 and the hole 122 opening to the interior of the occluding balloon 118. Similarly, the sealing balloon 120 is in fluid communication with the filling port 98 through the filling lumen 108 and the hole 124 opening to the interior of the sealing balloon 120. The occluding balloon 118 preferably includes a semi-compliant material (such as nylon) or a compliant material (such as polyurethane), which enables the balloon to conform to the diameter of the blood vessel to partially or completely occlude antegrade blood flow. The sealing balloon 120 preferably comprises a relatively rigid material (e.g., polyethylene terephthalate) that maintains its shape during expansion so as to closely conform to the entry wound of the cannula 82 into the blood vessel. In particular, if the insertion site begins to bleed during operation of the pump 84, the sealing balloon 120 (if provided) can be filled through the filling port 98, thereby stopping the bleeding and directing the blood flowing out of the incision 112 to the patient's limbs.

[0052] See also Figure 4A and Figure 4B , alternative structures for more evenly distributing blood flowing from the cutout 70 of the cannula 52 of FIG. 2 or the cutout 112 of the cannula 82 of FIG. 3 are now described. Figure 4A 3, a portion of the cannula 82 is depicted, the cannula having a plurality of cutouts 112' and an occlusion balloon 118' placed distal to the cutouts 112'. When inflated, the occlusion balloon 118' is concave 125, so that blood flowing out of the cutouts 112' impacts the proximal surface of the balloon and is redirected in the antegrade direction. The occlusion balloon 118' can be molded into the concave shape 125 during manufacturing. In this way, blood reperfused into the blood vessel from the extracorporeal pump can be more evenly redistributed within the blood vessel and directed in the antegrade direction without directly impacting the blood vessel wall.

[0053] Figure 4B An optional structure is shown that can be used to distribute blood returning through the incision 70 of the cannula 52 or the incision 112 of the cannula 82. The diffuser 130 includes a thin walled shrink tube 132 including a plurality of holes 134 and attached to the cannula above the incision 70 of the cannula 52 or the incision 112 of the cannula 82 to more evenly distribute blood returning from the extracorporeal pump. In particular, the diffuser 130 can be bonded to the cannula along line 136 using heat welding or a suitable biocompatible glue. The diffuser 130 reduces the risk of blood returning to the blood vessel through the incision being ejected at high speed onto the blood vessel wall. In addition, the diffuser 130 can be easily flushed with saline before use without causing the cannula to become bulky or hindering insertion. Figure 3A and Figure 3B In this embodiment, it is desirable to place a local blood pressure sensor in the blood vessel downstream of diffuser 130.

[0054] Figure 5A and 5B Describes the Figure 3A and Figure 3B

[0066] Additional modifications are made to the sleeve 82 of the embodiment. Figure 5A and Figure 5B The distal end of an irrigation cannula (e.g., cannula 82) is depicted, and omitting an invasive or circulatory assist device that may extend through the inlet lumen and distal end of the cannula. Figure 5A In an embodiment, the occluding balloon 118 and the incision 112 are combined into a double-layer balloon 140. The balloon 140 can be formed of a semi-compliant material (such as nylon) or a compliant material (such as polyurethane), and includes an upper compartment 142 and a lower compartment 144 separated by a liquid impermeable membrane 145. The sealed upper compartment 142 can be configured to expand and contact the vessel wall when saline is injected through the hole 122. The lower compartment 144 is in communication with the incision 112 and includes a lower surface 146 having a plurality of perforations 146.

[0055] exist Figure 5A In the arrangement of the upper compartment 142 of the balloon 140, the upper compartment 142 acts to partially or completely occlude the blood vessel, while the lower compartment 144 delivers blood to the distal blood vessel. Optionally, a single balloon may be used instead of the double-layer balloon 140, although a double-layer structure (more preferably a disc shape) of the balloon 140 may be desirable to shorten the balloon so that it can be easily inserted into a highly atherosclerotic blood vessel. In addition, the plurality of perforations 146 will ensure that blood is reperfused into the blood vessel, away from the vessel wall. Figure 5B Depicts an alternative embodiment of a double-layer balloon having Figure 5AThe double-layer balloon 150 is mainly different from the balloon 140 in that the upper surface of the balloon 150 is formed into a funnel shape 152, and the perforated lower surface 154 of the balloon can also be inclined relative to the blood vessel wall to further distribute the blood reperfused into the blood vessel. Figure 5A and 5B In this embodiment, it is desirable to place the vascular pressure sensor within the blood vessel downstream of the perforated lower surface 154.

[0056] Now refer to Figure 6 , describes a further optional embodiment of the perfusion system of the present invention. Figure 6 For the sake of clarity, the Figure 2A and Figure 3A The cannula 160 is a double lumen cannula, as described above with respect to Figure 2A The balloon 162 is attached to the cannula so that the interior of the balloon 162 is connected to the incision 164, and an extracorporeal pump (such as Figure 2A The pump 76 in the extracorporeal pump delivers blood to the blood vessel through the incision 164. The balloon 162 includes a plurality of perforations 166 in its lower surface. Thus, when the blood from the extracorporeal pump is delivered to the interior of the balloon 162, the balloon 162 at least partially expands to block the blood vessel. The blood then flows out of the balloon 162 through the plurality of perforations 166 and flows in an antegrade manner to the patient's limbs. Figure 6 In such embodiments, it is desirable to place a vascular pressure sensor within the vessel downstream of balloon 162.

[0057] Figure 7 A further alternative embodiment of a perfusion system constructed in accordance with the principles of the present invention is depicted. System 170 differs from the previous embodiments in that its inlet catheter can be used to perform an interventional procedure, for example, to treat peripheral arterial disease, and thereafter used as part of a perfusion system to reduce the risk of limb ischemia. Figure 7 As depicted, system 170 includes an inlet cannula 172 and a return conduit 174 connected to an extracorporeal pump 176 via tubing 178. Extracorporeal pump 176 may be any of the pumps described herein.

[0058] The distal end 180 of the inlet cannula 172 has an inlet 182, the proximal end 184 includes an outlet port 186 and a hemostasis port 188, and an inlet lumen 190 extends between the distal end 180 and the proximal end 184 and is also in fluid communication with the outlet port 186. The inlet cannula 172 is configured to be placed in a limb, such as an arm or leg, in an antegrade manner for performing an interventional procedure. Once the treatment is completed, the inlet cannula 172 can be left in place and used as part of a perfusion system, as described below.

[0059] The flashback cannula 174 has a proximal end 192 including an inlet port 194, an outlet port 196, and a lumen 198 extending therebetween. The flashback cannula 174 is preferably longer than the inlet cannula 172 and has a selected diameter so that when inserted through the inlet cannula 172, an annulus 200 is formed in the inlet lumen 190 to allow blood to be drawn into the extracorporeal pump 176 through the inlet 182, the annulus 200, and the outlet port 186. The flashback cannula 174 is inserted through the hemostasis port 188. The inlet and outlet cannulas can then be connected to the extracorporeal pump 176 via tubing 178. During operation, the pump 176 draws blood into the pump through the inlet 182, the annulus 200, and the outlet port 186, and then discharges the blood into the blood vessel in an antegrade direction through the inlet port 194, the lumen 198, and the outlet port 196 of the flashback cannula 174 at a controlled pressure or flow rate determined by the pump 176 based on user input or determined by the pump controller. Optionally, a return cannula 174 may be placed in the patient's contralateral arm or leg, should this be desired to reduce the risk of limb ischemia.

[0060] In further embodiments, an inlet cannula can be inserted into more than one artery or vein, and the blood delivered by the extracorporeal pump can be reperfused to more than one limb. For example, the extracorporeal pump can include two or more inlets, so that one inlet can be connected to a cannula located in an artery, and a second inlet can be connected to a cannula placed in a limb vein. The blood delivered by the extracorporeal pump can be reperfused into an artery downstream of the blockage, while venous blood can be drawn from a limb, thereby forming a further gradient to enhance the perfusion of the limb. Alternatively, the extracorporeal system of the present invention can be configured to have only a single inlet, but with multiple outlets, so that the oxygenated blood introduced into the pump can be reperfused in multiple limbs. In another optional embodiment, a reflux cannula can deliver blood to the afferent lymphatic vessels of the lymphatic system to reduce or prevent venous thrombosis, peripheral edema or lymphedema.

[0061] Now refer to Figure 8 , which is an exemplary mechanism 210 of a roller pump suitable for use as an extracorporeal pump for a perfusion system. As will be appreciated by those skilled in the art of pump design, mechanism 210 includes a rotor 212 with three or more rollers 214. Rollers 214 are in contact with plastic tubing 216, which is connected to an inlet port 218 and an outlet port 220 of the pump. Rotor 212 is mounted on a shaft 222, which is connected to a motor (not shown) directly or through a suitable gear train, such that rotation of the rotor causes rollers 214 to run along plastic tubing 216 to push blood in the tubing from inlet port 218 to outlet port 220. U.S. Patent No. 3,963,023 to Hankinson provides Figure 8Additional details of roller pumps of the type depicted are incorporated herein by reference. A suitable alternative blood pump design capable of producing pulsatile flow is described in U.S. Pat. No. 9,295,767 to Schmid, also incorporated herein by reference. U.S. Pat. No. 4,468,177 to Strimling, also incorporated herein by reference, describes a diaphragm pump suitable for use as an extracorporeal pump in the perfusion system of the present invention.

[0062] Now refer to Fig. 9A , 9B and 9C, describe a piston mechanism used as an extracorporeal pump in the system of the present invention. The pump 230 includes a piston 232, which is disposed in a chamber 234 for reciprocating motion, and the chamber 234 is connected to an inlet 236 and an outlet 238. It will be understood by those skilled in the art of pump design that the piston 232 is connected to a motor via a gear system (not shown) that periodically advances and retracts the piston head in the chamber 234. A one-way valve 240, such as a butterfly valve or a flap valve, is located at the distal end of the inlet 236, and another one-way valve 242 is located at the proximal end of the outlet 238. A pressure sensor 244 monitors the pressure in the catheter distal to the outlet 238. At Fig. 9A , pump 230 exhibits an isobaric state, where blood is not being drawn into or out of chamber 234. If pressure sensor 244 detects a high pressure in the catheter while the vascular pressure sensor detects a low pressure, this may indicate a blockage, clot, or kink in the tubing. The controller may issue an alarm signal when it detects a pressure differential exceeding a predetermined threshold.

[0063] Fig. 9B The suction stroke of the pump 230 is depicted, during which the inlet valve 240 opens to allow blood to be drawn into the chamber 234 during the retraction of the piston 232. During this stage of operation, the one-way valve 242 is closed and the pressure sensor 244 records a negative pressure. Once the piston reaches a minimum stroke, it reverses direction, causing the one-way valve 240 to close and the one-way valve 242 to open, thereby allowing blood to flow through the outlet 238. During this stage of operation, the pressure sensor 244 records a positive pressure. When the piston 232 reaches a maximum stroke, it begins to move in the opposite direction, causing the one-way valve 242 to close and the one-way valve 240 to open again. In this way, depending on the speed at which the motor and gear train drive the piston 232, a specified blood flow or pressure can be obtained at the outlet 238. Child's U.S. Patent No. 4,221,548 describes an optional embodiment of a piston pump, which is incorporated herein by reference and is suitable for use in the perfusion system of the present invention.

[0064] Fig. 10A and Fig. 10B Schematic diagrams of an extracorporeal pump and software for operating the system, respectively. More specifically, Fig. 10A2 is a schematic diagram depicting the functional modules of an extracorporeal pump 250 for use in the perfusion system of the present invention, including a processor 252 coupled to a non-volatile memory 254, such as a flash memory, an electrically erasable programmable read-only memory and / or a hard disk, and a volatile memory 256 via a data bus. The processor 252 is electrically coupled to a motor 258, a plurality of sensors 260, a user interface 262, and a valve controller 264. The motor 258 may include a separate dedicated controller that interprets and drives the motor 258 according to instructions from the processor 252.

[0065] about Fig. 10B As described, processor 252 executes programming stored in non-volatile memory 254 to control the operation of motor 258 based on signals generated by sensor 260 and input from user interface 262. As described below, processor 252 is configured to monitor the operation of motor 258 (and any associated motor controller) and sensor 260, and store data reflecting the operation of the pump, including event logs and alarms.

[0066] The non-volatile memory 254 preferably comprises flash memory, EEPROM, or a solid state or hard disk, and stores a unique device identifier for the pump, as well as firmware and programming executed by the processor 252, configuration set point data related to the operation of the pump. The volatile memory 256 is coupled to the processor 252 and supports the operation of the processor 252, and stores data and event log information collected during the operation of the pump 250.

[0067] The motor 258 is of a type selected as described above for driving the pumping mechanism of the extracorporeal pump. The user interface 262 may include an input device, such as corresponding to the display panels 17 and 77 described above, or include input keys and a display for displaying input pump operating parameters, pump status, and sensor data. The sensor 260 may include pressure sensors at the pump inlet and outlet ports, pressure sensors in the artery or vein upstream of the inlet cannula inlet and downstream of the return cannula outlet, blood and / or tissue oxygenation sensors, such as NIRS, pH and / or lactate level sensors, and flow sensors for determining the flow rate of blood through the pump. The sensor 260 may be monitored by the processor 252 to determine the inlet and outlet blood pressure, tissue oxygenation, and whether an obstruction has occurred within the blood circuit.

[0068] Processor 252 may communicate with valve controller 264; optionally, valve controller 264 may be part of the functionality of processor 252. Valve controller 264 controls actuation of any valves that may be used to control the flow of blood from an inlet port to an outlet port. 9A to 9C In an embodiment, the valve controller 264 can also coordinate the actuation of the one-way valve.

[0069] Now go to Fig. 10B , describes the operation Fig. 10A The software 270 for the extracorporeal pump 250 is implemented in the form of programming, which is executed by the processor 252 to control the operation of the extracorporeal pump motor 258, etc. The software 270 includes a plurality of functional modules, including a main module 272, a sensor module 274, an alarm detection module 276, an event recording module 278, a user interface module 280, a configuration setting module 282, and an AI module 284. In one embodiment, the software is configured to be in Microsoft (registered trademark of Microsoft Corporation, Redmond, Washington) or Unix-based operating systems.

[0070] The main module 272 preferably consists of a main software routine that executes on the processor 252 and controls the overall operation of the other functional modules. The main module 272 enables the operator to input pump operating data through the user interface 280 and the user interface 262, and displays pump operation and status data, including pump outlet pressure and / or flow rate, local blood pressure, tissue oxygenation level and alarm limit data. The main module 272 also controls the operation of the motor 258 and the monitoring of the sensor through the sensor module 274.

[0071] The alarm detection module 276 may include routines for evaluating data received from the sensor 260 to determine the occurrence of an abnormal condition for the operator's attention. For example, the alarm detection module 276 may be configured to alert the operator to deviations in sensor data from preset values, or to identify potential occlusions that affect pump operation, or displacement of the catheter from the lumen of a vessel. The alarm detection module 276 may also be configured to detect increases in vascular resistance and / or pressure in the patient's limbs, as well as potential slow flow conditions that may lead to limb ischemia. In addition, the alarm detection module 276 may be configured to detect a decrease in limb tissue oxygenation. Such an alarm may be communicated to the operator via a display of the user interface 262. The event log module 278 may store this information in the non-volatile memory 254 to create a record of pump operation data, including pump operation time and pressure / flow data.

[0072] The user interface module 280 is responsible for receiving operator input data and displaying information about the operating status of the pump in an intuitive, easy-to-understand format for the operator to view. The configuration settings module 282 is a routine that configures the parameters stored in the non-volatile memory 254 that control the operation of the pump 250, including the desired pump output pressure, local blood pressure, flow rate, tissue oxygenation, and any limit values ​​used to evaluate the occurrence of alarm conditions. The module 282 can also configure parameters stored in the non-volatile memory 254 related to the operational control of the processor 252 and the motor 258.

[0073] The AI ​​module 284 may include programming that allows the extracorporeal pump to automatically optimize local blood pressure and tissue oxygenation levels for a particular patient to reduce the risk of limb ischemia. In particular, the AI ​​module 284 may include programming to initiate pump operation at a pressure and / or tissue oxygenation level initially set by a human operator. The AI ​​module may then step through a range of pump speeds to adjust the flow rate based on the monitored limb pressure data and / or the monitored tissue oxygenation level while monitoring the pressure in the patient's limbs. In one embodiment, the AI ​​module 282 may then continue further pump operation by selecting the pump speed that produces the highest monitored flow rate at the lowest pressure.

[0074] In an optional embodiment, the AI ​​module 282 may be configured to activate a built-in or inline ECMO system if it is determined that the increased flow rate or local blood pressure is insufficient to maintain a target oxygenation level in the extremity tissue. In a further embodiment, the AI ​​module 282 may activate the ECMO to cause high pressure oxygenation of the blood to further increase tissue oxygenation. In yet another embodiment, the pump circuit may act as a passive bypass until the sensor 260 detects that the tissue oxygenation level has dropped below the target value. When the tissue oxygenation level is detected to have dropped below the target value, the AI ​​module 282 may then activate the pump to increase the local blood pressure in the reperfused area.

[0075] Preliminary experimental observations

[0076] The reperfusion pump system and method of the present invention were initially tested in a porcine model, and the test results showed unexpected beneficial results as described below.

[0077] Vascular pressure control pump and passive bypass

[0078] Fig.11 is a screenshot of a display depicting blood pressure and oxygen saturation in the blood vessels of a pig's leg. In this experiment, the pump circuit of the present invention was used to create a blood circuit from the carotid artery to the left leg (above), while a passive circuit was created by inserting one end into the other carotid artery and the other end into the right leg (below). Continuous NIRS measurements were taken on both legs to determine the absolute tissue saturation (StO2) level at each stage of the reperfusion process, and the digital readout on the right side of the chart shows the StO2 level at the end of the experiment. The top line of each chart represents the reference value for the non-occluded area of ​​the animal (81% for the right leg; 73% for the left leg). The lower line of the upper figure (expressed as 77% StO2) corresponds to the NIRS measurement of the StO2 level after occlusion of the left leg (using the pump circuit of the present invention). The lower line of the lower figure (expressed as 55% StO2) corresponds to the NIRS measurement of the StO2 level of the right leg in passive bypass only.

[0079] At the beginning of the NIRS measurement, both legs were occluded without any form of reperfusion to reduce the StO2 level in each leg. Once a quasi-static level was reached, NIRS measurements were recorded for five minutes before reperfusion began. After five minutes, as indicated by the asterisk (*), the passive bypass and the pump system of the present invention were started simultaneously. As can be seen from the left leg (top figure), the perfusion controlled by vascular pressure resulted in a higher perfusion of the leg tissue, as shown by the steep curve with an end point of 77% StO2. The right leg (bottom figure) shows that the passive bypass has almost no reperfusion value, as shown by the flat curve with an end point of 55% StO2. This experiment shows that the passive system is not as effective in oxygenating the tissue as the pump circuit of the present invention that controls vascular blood pressure.

[0080] Absolute tissue saturation (StO2) and blood oxygen partial pressure (PaO2)

[0081] Fig. 12A and Fig. 12B Results are presented for a second experiment in which ischemia was induced in one leg of a pig by occluding blood flow (closing the iliac artery), followed by passive bypass reperfusion and then vascular controlled pressure reperfusion using the pump system of the present invention. Fig. 12A The StO2 level is plotted over five consecutive time intervals, while Fig. 12B PaO2 levels are depicted over the same five time intervals. Point 1 represents the baseline levels of StO2 and PaO2 measured before occlusion occurred. Point 2 corresponds to occlusion of the leg for 20 minutes to induce ischemia, as shown by the sharp drop in both levels. Point 3 corresponds to passive bypass being provided for approximately 15 minutes, ending at point 4. Notably, during passive bypass, blood oxygenation levels rose dramatically (reaching 246.9), even though tissue oxygenation, as determined by NIRS measurements, showed barely any increase, from 27% StO2 to only 28% StO2. Fig. 12A and Fig. 12B At point 4 in the figure, the passive bypass is terminated for approximately 90 seconds to allow the limb to return to an ischemic state. Next, from point 4 to point 5, the vascular pressure control system described herein is activated. One minute later, the blood oxygenation level returns to normal, rising from 128.8PaO2 to 315.5PaO2. Importantly, however, the tissue oxygen content measured by the NIRS sensor also rises significantly, from 15% StO2 to 41% StO2. The above preliminary results indicate that reperfusion of the ischemic limb under controlled vascular pressure provides a much higher oxygen uptake than flowing physiological flow rates alone. Applicants believe that the amount of oxygen exchange caused by vascular blood pressure in the capillary bed of the limb is higher than that which can be achieved by simply providing physiological flow rates to the reperfused vessels.

[0082] While various illustrative embodiments of the present invention have been described above, it will be apparent to those skilled in the art that various changes and modifications can be made thereto without departing from the invention.

Claims

1. A perfusion system for use in a patient's limb with antegrade blood flow obstruction due to thrombosis, trauma, or medical surgery / device, the perfusion system comprising: an inlet cannula configured to be placed in a patient's blood vessel, the inlet cannula having a proximal end, a distal end, and a lumen extending from the proximal end to the distal end, an inlet located at the distal end, an outlet port and a hemostasis port located at the proximal end, wherein the inlet and the hemostasis port are in communication with the lumen, and the hemostasis port is configured to allow an interventional or circulatory assist device to be inserted through the lumen to form an annular lumen in communication with the outlet port; a flashback lumen having a proximal end and a distal end, the distal end of the flashback lumen being configured to be placed in a blood vessel of a patient downstream of the occlusion; and an extracorporeal pump configured to couple to the outlet port of the inlet cannula and the proximal end of the flashback lumen, wherein the extracorporeal pump is configured to draw blood through the inlet of the inlet cannula and deliver blood at a selected local pressure at the distal end of the flashback lumen without interfering with the operation of the invasive or circulatory assist device.

2. The perfusion system of claim 1, wherein the flashback lumen is placed in a flashback cannula.

3. The perfusion system of claim 1, wherein the flashback lumen comprises a second lumen of the inlet cannula, and the distal end of the flashback lumen defines a cutout in a side surface of the inlet cannula.

4. The perfusion system of claim 1, wherein the inlet catheter further comprises an occlusion balloon that at least partially occludes flow within the vessel antegrade to the inlet of the inlet cannula.

5. The perfusion system of claim 4, wherein the inlet catheter further comprises a first filling port located at the proximal end of the inlet cannula and a first filling lumen extending from the first filling port through the inlet cannula to the occlusion balloon.

6. The perfusion system of claim 4, wherein the inlet cannula further comprises: a sealing balloon placed adjacent to the occluding balloon; a second filling port located at the proximal end of the inlet cannula; and A second filling lumen extends from the second filling port through the inlet cannula to the sealing balloon.

7. The perfusion system of claim 1, wherein the extracorporeal pump further comprises an extracorporeal membrane oxygenation system.

8. The perfusion system of claim 1 , wherein the extracorporeal pump is in communication with a sensor that measures at least one of tissue oxygenation, pH level, and lactate level of the occluded limb and is programmed to adjust vascular pressure or flow rate to achieve a target tissue oxygenation level.

9. The perfusion system of claim 1, wherein the flashback lumen comprises a second lumen of the inlet cannula, the inlet catheter further comprises an occlusion balloon having a plurality of perforations, and the distal end of the flashback lumen communicates with an interior of the occlusion balloon.

10. The perfusion system of claim 1, wherein the extracorporeal pump is programmed with an AI module that is automatically configured to determine a preferred flow rate to achieve a target local pressure that reduces the risk of limb ischemia.

11. The perfusion system of claim 1 , wherein the extracorporeal pump is in communication with a pressure sensor located in a patient's blood vessel antegrade from the distal end of the flash lumen and is programmed to monitor the pressure sensor to determine if occlusion has occurred.

12. A perfusion system comprising: at least one inlet cannula configured to be placed in the vasculature of a patient, the at least one inlet cannula having a proximal end, a distal end, and a lumen extending from the proximal end to the distal end, an inlet located at the distal end, an outlet port disposed on the proximal end, wherein the inlet communicates with the lumen; at least one flashback lumen having a proximal end and a distal end, the distal end of the at least one flashback lumen being configured to be placed in the vasculature of a patient at one or more locations downstream of an inlet of the at least one inlet cannula; and an extracorporeal pump configured to couple to the outlet port of the at least one inlet cannula and the proximal end of the at least one return lumen; The extracorporeal pump is configured to draw blood through the inlet of the at least one inlet cannula and deliver the blood through the distal end of the at least one flashback lumen at a selected local pressure.

13. The perfusion system of claim 12, wherein the at least one return lumen is disposed in at least one return cannula, and wherein the at least one inlet cannula further comprises a hemostasis port disposed on the proximal end, the hemostasis port being configured to allow an interventional or circulatory assist device to be inserted through the lumen to form an annular cavity communicating with the outlet port.

14. The perfusion system of claim 12, wherein the at least one flashback cannula is configured to be inserted through the hemostasis port of the at least one inlet cannula to form an annulus communicating with the outlet port of the at least one inlet cannula.

15. The perfusion system of claim 12, wherein the extracorporeal pump is selected from a vane pump, a centrifugal pump, a roller pump, an axial flow pump, a diaphragm pump, and a piston pump, and wherein the extracorporeal pump is configured to generate a pulsatile flow at the distal end of the return lumen.

16. The perfusion system of claim 12, wherein the return lumen further comprises at least one delivery port configured to deliver one or more reperfusion protectants or donor blood for infusion.

17. The perfusion system of claim 12, wherein the extracorporeal pump comprises a motor and a controller that controls operation of the motor.

18. The perfusion system of claim 17, wherein the controller is programmed to maintain a selected local pressure at the distal end of the at least one flash lumen by adjusting the flow rate, wherein the selected local pressure is input via a user interface.

19. The perfusion system of claim 17, wherein the controller is programmed with an AI module that is automatically configured to determine a preferred flow rate to achieve a target local pressure that reduces the risk of limb ischemia.

20. The perfusion system of claim 17, wherein the extracorporeal pump is in communication with a pressure sensor in the patient's vasculature located distally downstream of the at least one return lumen, and wherein the controller is programmed to monitor the pressure sensor to determine if an occlusion has occurred, and wherein the controller is programmed to generate an alarm if the monitored pressure sensor deviates from a preselected limit.

21. The perfusion system of claim 12, wherein the extracorporeal pump comprises a first extracorporeal pump and a second extracorporeal pump, wherein the at least one inlet cannula comprises a first inlet cannula and a second inlet cannula, the first inlet cannula having a first inlet configured to be placed in a vein of the patient, the second inlet cannula having a second inlet configured to be placed in an artery of the patient, wherein the first extracorporeal pump is configured to draw blood through the first inlet and return the blood to the vein distal to the occlusion through the outlet, and wherein the second extracorporeal pump is configured to draw blood through the second inlet and deliver the blood to the artery distal to the occlusion through the outlet.

22. The perfusion system of claim 12, wherein the extracorporeal pump comprises a first motor and a second motor, wherein the at least one inlet cannula comprises a first inlet cannula and a second inlet cannula, the first inlet cannula having a first inlet configured to be placed in a vein of the patient, the second inlet cannula having a second inlet configured to be placed in an artery of the patient, wherein the motor is configured to draw blood through the first inlet and return the blood to the vein distal to the occlusion through the outlet, and wherein the second motor is configured to draw blood through the second inlet and return the blood to the artery distal to the occlusion through the outlet.

23. A perfusion system for returning blood accumulated in a cavity of a patient to systemic circulation, the perfusion system comprising: an inlet cannula configured to be placed in a patient cavity, the inlet cannula having a proximal end, a distal end, and a lumen extending from the proximal end to the distal end, an inlet located at the distal end, an outlet port disposed on the proximal end, and wherein the inlet communicates with the lumen; a flashback lumen having a proximal end and a distal end, the distal end of the flashback lumen being configured to be placed in a blood vessel of a patient; and An extracorporeal pump is configured to be connected to the outlet port of the inlet cannula and the proximal end of the flashback lumen, wherein the extracorporeal pump is configured to draw blood through the inlet of the inlet cannula and deliver blood at the distal end of the flashback lumen at a selected local pressure.

24. The perfusion system of claim 23, wherein the inlet cannula further comprises a hemostasis port communicating with the lumen, wherein the hemostasis port is configured to allow an interventional or circulatory assist device to be inserted through the lumen to form an annulus communicating with the outlet port.

25. The perfusion system of claim 23, wherein the patient cavity is the pericardium.

26. The perfusion system of claim 23, wherein the distal end comprises a pigtail catheter.

27. The perfusion system of claim 23, wherein the return lumen further comprises at least one delivery port configured to deliver one or more reperfusion protectants or donor blood for infusion.

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