Methods, systems and device for blood flow regulation

Abstract

Embodiments of the present disclosure are directed to a blood flow regulation device including a first flow opening and a second flow opening. Blood flowing between the blood flow openings is restricted such the pressure of the blood entering the blood flow regulation device has a pressure which is greater than blood downstream of the blood flow regulation device. In the present device the size of one flow opening which may be positioned upstream or downstream is modified to control the pressure drop across the blood flow regulation device, while the size of the other flow opening is expanded to the size of the vessel in which the blood flow regulation device is positioned. The size of the modifiable flow opening may be modified directly or modified through the use of a flow restriction device which may be positioned in or immediately adjacent the modifiable flow opening.

Description

e-filed RVMP-005 / 001WOSeptember 4, 2025 43730-02028METHODS, SYSTEMS AND DEVICE FOR BLOOD FLOW REGULATIONRELATED APPLICATIONS

[0001] The subject application claims benefit of and priority to U.S. provisional patent application nos. 63 / 691,220, filed September 5, 2024, and 63 / 823,557, filed June 13, 2025, each disclosure of which is incorporated herein by reference in its entirety.Field

[0002] Inventions and embodiments of the present disclosure relate to the vascular field, and more particularly, to the field of regulating blood flow in a blood vessel.Background

[0003] Congestive heart failure (CHF) is characterized by a progressive loss in the heart's ability to pump blood. Causes range from valvular disease to infection. The affected heart has difficulty in supplying blood to body organs with each contraction. Congestive heart failure symptoms typically include shortness of breath, fluid retention and general fatigue. Most patients with CHF require additional treatments to help manage their disease, typically oral diuretics, inotropes, vasodilators and beta-blockers.

[0004] CHF may be treated using pharmaceuticals. Diuretics help the kidneys rid the body of excess fluid, thereby reducing blood volume and the heart's workload. Inotropes strengthen the heart's pumping action. Vasodilators, such as ACE (angiotensin conversion enzyme) inhibitors, cause the peripheral arteries to dilate, making it easier for blood to flow. Beta-blockers slow the heart rate and reduce blood pressure by blocking the effects of adrenaline.

[0005] Despite such interventions, many congestive heart failure patients eventually experience rapid deterioration and worsening of symptoms. This sudden worsening ofe-filed RVMP-005 / 001WOSeptember 4, 2025 43730-02028 symptoms is called Acute Heart Failure (AHF) and refers to rapid onset or worsening of signs and symptoms of chronic heart failure.

[0006] AHF is a life-threatening medical condition requiring urgent treatment that often leads to urgent hospital admission (1 million admissions due to AHF annually in the US). Fluid decongestion using high doses of diuretics is an important treatment for AHF. Diuretics are a family of drugs designed to increase urine output and sodium secretion.

[0007] Acutely decompensated heart failure resulting in hospitalization marks a fundamental change in the natural history of the progression of congestive heart failure. Mortality rates in the year following hospitalization for acute heart failure patients are significantly higher than in non- hospitalized patients. Moreover, these patients are particularly prone to readmission, with recurrent hospitalization rates of 50% within 6 months of discharge.

[0008] A certain percentage of patients (20-30%) admitted to the hospital for AHF suffer from insufficient response to diuretics and do not achieve rapid fluid removal or complete decongestion. As of today, there are no viable therapies for AHF patients resistant to diuretics. These patients face risks of increased in-hospital mortality, longer hospital stays and high rates of 30-day readmission (23-26%).

[0009] It would, therefore, be advantageous to provide a device useful in the treatment of patients who are hospitalized with Acute Heart Failure and do not respond to treatment with diuretics or other drugs.SUMMARY

[0010] Embodiments of the present disclosure are directed to a blood flow regulation device including a first flow opening and a second flow opening. Blood flowing between the blood flow openings is restricted such the pressure of the blood entering the blood flow regulation device has a pressure which is greater than blood downstream of the blood flow regulation device. In the present device the size of one flow opening which may be positioned upstream or downstream is modified to control the pressure drop across the blood flow regulation device, while the size of the other flow opening is expanded to the size of the vessel in which the blood flow regulation device is positioned. The size of the modifiable flow opening may be modified directly or modified through the use of a flow restriction device whiche-filed RVMP-005 / 001WOSeptember 4, 2025 43730-02028 may be positioned in or immediately adjacent the modifiable flow opening.

[0011] These and other embodiments, objects, and advantages of the inventions disclosed herein will become even more evident by reference to the detailed description set out below, and accompanying figures, a brief description of which is provided below.BRIEF DESCRIPTION OF THE DRAWINGS

[0012] Fig. 1 is a drawing of a blood flow regulation device according to some embodiments of the present disclosure, whereby the device can be used to regulate blood flow through a body lumen such as, for example, the Inferior Vena Cava (IVC).

[0013] Fig. 2 is a drawing of an outer frame, according to some embodiments, for the blood flow regulation device of Fig. 1.

[0014] Fig. 3 is a drawing of a blood regulation element, according to some embodiments, for the blood flow regulation device of Fig. 1.

[0015] Fig. 4 is a first perspective view of the blood flow regulation device of Fig. 1 viewed from a proximal end, illustrating the flow of blood into the device.

[0016] Fig. 5 is a second perspective view of the blood flow regulation device of Fig. 1 viewed from a distal end, illustrating the diameter of the restrictor section of the blood regulation element.

[0017] Fig. 6 is a third perspective view of the blood flow regulation device of Fig. 1 viewed from a distal end, illustrating the cross-sectional area of the distal end of the device.

[0018] Fig. 7 is a fourth perspective view of the blood flow regulation device of Fig. 1 viewed from a distal end, illustrating the cross-sectional area of the restrictor section of the blood regulation element.

[0019] Fig. 8 is an illustration of the placement of the blood flow regulation device of Fig. 1 within in the inferior vena cava, according to some embodiments.

[0020] Fig. 9 is a fifth perspective view of the proximal end of the blood flow regulation device of Fig. 1, illustrating the adaptation of the device for insertion through the jugular vein, according to some embodiments.

[0021] Fig. 10 is a side view of a blood flow regulation device when positioned within ae-filed RVMP-005 / 001WOSeptember 4, 2025 43730-02028 vessel such as an inferior vena cava, according to some embodiments.

[0022] Fig. 11 is an end view of the blood flow regulation device in Fig. 10.

[0023] Fig. 12 is a side view of a blood flow regulation device positioned within a vessel, such as an inferior vena cava, according to some embodiments, illustrating the device when placed in a vessel with a smaller diameter than the vessel illustrated in Fig. 10.

[0024] Fig. 13 is an end view of the blood flow regulation device shown in Fig. 12.

[0025] Fig. 14 is a side view of a blood flow regulation device extending from a catheter, according to one or more embodiments.

[0026] Fig. 15 is a side view of the blood flow regulation device of Fig. 14 pulled into the catheter, according to one or more embodiments.

[0027] Fig. 16 is a side view of the blood flow regulation device of Figs. 14 & 15 positioned in an inferior vena cava, according to one or more embodiments.

[0028] Fig. 17 is a blood flow regulation device collapsible into a two-part catheter, according to one or more embodiments.

[0029] Fig. 18 is a first perspective view of a blood flow regulation device, according to one or more embodiments.

[0030] Fig. 19 is a perspective view of a blood flow regulation according to one or more embodiments.

[0031] Fig. 20 is a perspective view of the blood flow regulation device of Figs. 18 with a blood flow regulator, according to one or more embodiments.

[0032] Fig. 21 is a representative side view of the blood flow regulation device of Fig. 20, according to one or more embodiments.

[0033] Fig. 22 is a perspective view of a blood flow regulation device with a biconal element for the blood flow regulator, according to one or more embodiments.

[0034] Fig. 23 is a representative side view of the blood flow regulation device of Fig. 22 with the biconal element for the blood flow regulator, according to one or more embodiments.

[0035] Fig. 24A is a side view of a first embodiment of a blood flow regulator.

[0036] Fig. 24B is a side view of a second embodiment of a blood flow regulator.e-filed RVMP-005 / 001WOSeptember 4, 2025 43730-02028

[0037] Fig. 25 is a perspective view of the blood flow regulation device of Fig. 19 with the blood regulator including a balloon positioned downstream, according to one or more embodiments.

[0038] Fig. 26 is a representative view of the blood flow regulation device of Fig. 25 according to one or more embodiments.

[0039] Fig 27 is a representative side view of the blood flow regulation device of Fig. 26 with the biconal element for the blood flow regulator, according to one or more embodiments.

[0040] Fig. 28 is a side view of a blood flow regulation device including a membrane 2 covering at least a portion of the frame, according to one or more embodiments.

[0041] Fig. 29 is a side view of the blood flow regulation device of Fig. 26 pulled into a catheter, according to one or more embodiments.DETAILED DESCRIPTION

[0042] Fig. 1 is a drawing of a blood flow regulation device 10 according to the present disclosure whereby blood flow regulation device 10 is designed to regulate blood flow through a body lumen. As shown, in some embodiments, blood flow regulation device 10 includes an outer frame 13, a blood regulation element 14, one or more (and preferably, in some embodiments, a plurality of) hook arms 12, and, in some embodiments, a snagging hook 11. Outer frame 13, which may be expandable and may be constructed of struts 30, which may be made of, for example, nitinol. In some embodiments of the disclosure, outer frame 13 is not covered by any membrane material and is permeable to fluids such as blood. Blood regulation element 14 may also be constructed of struts 30, which may be covered (at least one of the internal diameter and the external diameter of the element), at least in part (and in some embodiments, a majority, and in some embodiments, substantially all, and in some embodiments, all), by membrane 22. Membrane 22 may be impermeable to fluids such as blood (and in some embodiments, preferably impermeable to fluids). Outer frame 13 may be connected to inner frame 15 of blood regulation element 14 at connection points 18 via techniques familiar to those skilled in the art (e.g., welding). Arrow 24 represents the direction of blood flow through blood flow regulation device 10 and blood flow regulation device 10 may have an outer surface 44. Central axis 20, represented by the dashed linee-filed RVMP-005 / 001WOSeptember 4, 2025 43730-02028 which illustrates the central axis of blood flow regulation device 10 which may also be the central axis of one or more of outer frame 13, inner frame 15, blood regulation element 14 and / or a cylindrical restrictor section 16 having a length L. As also shown in Fig. 1, blood regulation element 14 may also include a conical section 32, which may include an outer surface 40, and a cylindrical section 34, which may include an outer surface 46.

[0043] Fig. 2 is an illustration of outer frame 13 of blood flow regulation device 10. Outer frame 13 may be a wire mesh of an appropriate material (e.g., nitinol), which can be a plurality of struts 30 which can also form an outer surface 44. Outer frame 13 may be connected to blood regulation element 14 at connection points 18 (see Fig. 1), which may be positioned at one or both of the proximal and distal ends of blood regulation device 10. In some embodiments, outer frame 13 is only connected to blood regulation element 14 at the proximal and distal ends of blood regulation device 10. Fig. 2 also illustrates central axis 20 of outer frame 13 (dashed line). Outer frame 13 may, in some embodiments form cylindrical section 34.

[0044] Fig. 3 is an illustration of a blood regulation element 14 of blood flow regulation device 10, according to some embodiments. Blood regulation element 14 may be shaped to control the flow of blood through blood flow regulation device 10 and may include three sections: a conical section 32, a cylindrical restrictor section 16, and an outlet section 134. As noted above, blood regulation element 14 may be formed by inner frame 15 which can include struts 30. Aportion ofinner frame 15, in some embodiments, canform conical section 32 and may be covered by membrane 22. In some embodiments of the disclosure, the portion of inner frame 15 which forms cylindrical restrictor section 16 may also be covered by membrane 22. In Fig. 3, central axis 20 (as represented by a dashed line) may be the center line of blood regulation element 14 and cylindrical restrictor section 16. Blood regulation element 14 may include first flow opening 36 (at a proximal end of blood regulation element 14) which may be positioned at a proximal end of conical section 32. In embodiments of the invention first flow opening 36 may also be referred to as an inlet opening or a proximal flow opening. As shown (Fig. 3), cylindrical restrictor section 16 may include a length L.

[0045] Fig. 4 is a first perspective view of the proximal end of blood flow regulation device 10, illustrating the flow of blood (see arrows 24) into (a proximal end) and out of (a distal end) blood flow regulation device 10. First flow opening 36 through which blood enters blood flow regulation device 10 can be positioned at the proximal end of blood flowe-filed RVMP-005 / 001WOSeptember 4, 2025 43730-02028 regulation device 10, such that blood entering first flow opening 36 can be guided through conical section 32 by membrane 22. Membrane 22 may be positioned on the struts 30 of inner frame 15, which can form conical section 32 of blood regulation element 14. Blood flowing through blood regulation element 14 can be guided into cylindrical restrictor section 16 by conical section 32 and held within cylindrical restrictor section 16 by membrane 22 (which, in some embodiments, surrounds cylindrical restrictor section 16). Blood exiting cylindrical restrictor section 16 can pass into outlet section 134 and out of blood flow regulation device 10. In some embodiments, outlet section 134 is not covered by membrane 22, and blood flow regulation device 10 may be held in position within a vessel by the interaction between the vessel walls and outer surface 44 of outer frame 13 and blood flow regulation device 10.

[0046] Fig. 5 is a second perspective view of the distal end of blood flow regulation device 10 illustrating a distal view of cylindrical restrictor section 16 of blood regulation element 14. Cylindrical restrictor section 16 can include a diameter MD. In some embodiments, second flow opening 38 may be positioned at the distal end of cylindrical restrictor section 16 and blood exiting cylindrical restrictor section 16 can pass out through second flow opening 38. In embodiments of the invention second flow opening 36 may also be referred to as an outlet opening or a distal flow opening. In some embodiments, membrane 22 is configured to constrain the flow of blood through blood regulation element 14 and out second flow opening 38. In some embodiments, MD may be the diameter of second flow opening 38 and may be modified by constraining blood flow regulation device 10 in a vessel. In some embodiments, a reduction in the diameter of the vessel results in a reduction of MD and an increase in the diameter of the vessel results in an increase of MD. In some embodiments, the changes in diameter of the vessel are proportional to changes in MD, and thus, the diameter MD and blood flowthrough cylindrical restrictor section 16 is reduced with reductions in the diameter of the vessel in which blood flow regulation device 10 is positioned and increased with increases in the diameter of the vessel in which blood flow regulation device 10 is positioned.

[0047] Fig. 6 is a third perspective view of the distal end of blood flow regulation device 10 which includes outer frame 13 and blood regulation element 14. Blood regulation element 14 may include conical section 32, cylindrical restrictor section 16 and second flow opening 38. In some embodiments, blood regulation element 14 is covered at least in part bye-filed RVMP-005 / 001WOSeptember 4, 2025 43730-02028 membrane 22 (in some embodiments, a majority of blood regulation element 14 is covered membrane 22, and in some embodiments, substantially all of blood regulation element 14 is covered by membrane 22, and in some embodiments, all of blood regulation element 14 is covered by membrane 22) so as to guide the flow of blood into and through cylindrical restrictor section 16. A cross-sectional area SD of blood flow regulation device 10, in some embodiments, corresponds to the diameter or blood regulation device 10 at the distal end of blood regulation device 10.

[0048] Fig. 7 is a fourth perspective view of the distal end of blood flow regulation device 10 including outer frame 13 and blood regulation element 14. In some embodiments, the blood regulation element 14 is covered at least in part by membrane 22 (in some embodiments, a majority of blood regulation element 14 is covered membrane 22, and in some embodiments, substantially all of blood regulation element 14 is covered by membrane 22, and in some embodiments, all of blood regulation element 14 is covered by membrane 22) so as to guide the flow of blood into and through cylindrical restrictor section 16. In embodiments Cross-sectional area SMD corresponds to the cross-sectional area of second flow opening 38.

[0049] Fig. 8 is an illustration of the placement of blood flow regulation device 10 after positioning blood flow regulation device 10 within the inferior vena cava (IVC) 26. In some embodiments, blood flow regulation device 10 is positioned in the IVC upstream from renal veins 28 and can be held in position within inferior vena cava 26 by outer frame 13 which engages an inner wall of inferior vena cava 26.

[0050] In some embodiments, blood exits blood flow regulation device 10 at the intersection of renal veins 28 with IVC 26. In some embodiments, blood exits blood flow regulation device 10 upstream of renal veins 28. As shown in Fig. 8, the direction of blood flow is indicated by arrows 24, and specifically, blood flowing in inferior vena cava 26 enters blood flow regulation device 10 through first flow opening 36 and is then channeled through blood regulation element 14, including through conical section 32, through cylindrical restrictor section 16, into outlet section 134 and exits blood flow regulation device 10 through second flow opening 38. In some embodiments, blood is channeled through blood regulation element 14 by membrane 22. For example, blood may be channeled through conical section 32 by membrane 22, and / or blood may be channeled through cylindrical restrictor section 16 by membrane 22.e-filed RVMP-005 / 001WOSeptember 4, 2025 43730-02028

[0051] Fig. 9 is a fifth perspective view of the proximal end of blood flow regulation device 10 blood flow regulation device 10, according to some embodiments, which has been adapted for insertion through the jugular vein. In such embodiments, hook arms 12 and snagging hook 11 can be attached to the distal end of blood flow regulation device 10. In some embodiments, snagging hook 11 is connected to blood flow regulation device 10 by hook arms 12, and is used to remove blood flow regulation device 10 from a vessel (e.g., the inferior vena cava 26) when required.

[0052] As shown in Figs. 10-13, the blood flow regulation device of Fig. 1 is illustrated inserted it into two different diameter IVCs. Fig. 10 is a side view showing blood flow regulation device 10 positioned an inferior vena cava (IVC) 26 with a diameter DVCL. Fig. 12 is a side view showing blood flow regulation device 10 positioned an inferior vena cava IVC 26 with a diameter Dvcs. In the embodiments of the disclosure illustrated in Figs. 12 and 13 DVCL is larger than Dvcs.

[0053] Fig. 10 is a side view of blood flow regulation device 10 positioned in a vessel, such as an inferior vena cava 26. As noted in the figure, inferior vena cava 26 includes a diameter of DVCL. Fig. 11 is an end view of the blood flow regulation device 10 in Fig. 10 and Fig. 12 is a side view of a blood flow regulation device 10 positioned in a vessel, such as an inferior vena cava 26, similar to that which is illustrated in Fig. 10. However, as noted above, in Fig. 12, inferior vena cava has a diameter of Dvcs, which is smaller than the diameter DVCL of the inferior vena cava illustrated in Fig. 10. Fig. 13 is an end view of the blood flow regulation device in Fig. 12.

[0054] In Fig. 12, inner wall 48 of inferior vena cava (IVC 26) compresses and elongates blood flow regulation device 10 such that, as shown in Fig. 13, the diameter MDS of cylindrical restrictor section 16 is smaller than the diameter MDL of cylindrical restrictor section 16. Thus, when the device is positioned in the larger IVC in Fig. 11 the diameter DVCL will be larger than the diameter Dvcs when the device is positioned in the smaller IVC. The larger diameter MDL of cylindrical restrictor section 16 in Fig. 11 will result in a larger cross section SMDL of cylindrical restrictor section 16. Thus, controlling the flow of blood through blood flow regulation device 10 in proportion to the size of the IVC in which blood flow regulation device 10 is positioned. The smaller diameter MDS of cylindrical restrictor section 16 in Fig. 13 will result in a smaller cross section SMDS of cylindrical restrictor section 16, restricting the flow of blood through blood flow regulation device 10 more thane-filed RVMP-005 / 001WOSeptember 4, 2025 43730-02028 the flow of blood in the embodiment illustrated in Fig. 11.

[0055] Accordingly, it is a feature of some embodiments of the present disclosure that blood flow is controlled in proportion to diameter of the vessel (for example the IVC, in which blood flow regulation device 10 is positioned); specifically, in a smaller diameter IVC, the flow of blood will be proportionally less than the flow of blood in a larger diameter IVC. Accordingly, in some embodiments, the diameter of the IVC in which blood flow regulation device 10 is placed will determine the cross-sectional area of cylindrical restrictor section 16 and the rate of blood flow through blood flow regulation device 10.

[0056] Accordingly, as expressed above, in some embodiments, blood flow regulation device 10 is designed to regulate blood flow through a body lumen, such as Inferior Vena Cava 26. The blood flow regulation device 10 may be radially compressible to fit inside of a delivery cannula, such as, for example, catheter 21, which may be a canula, and which can be introduced into the body lumen using standard percutaneous techniques. Blood flow regulation device 10 may be introduced through either the groin or the jugular vein. Blood flow regulation device 10 is shown in Fig. 1 in its fully uncompressed state.

[0057] Blood regulation device 10 can include an outer frame 13 designed to engage the inner body lumen and provide radial support. Inner frame 15 provides support and structure for blood regulation element 14 which includes a generally tapering shape at a proximal end, tapering down in the direction of blood flow (in Fig. 1, the blood flows from left to right). Inner frame 15 may be partially or fully coated by membrane 22. Membrane 22 may be partially or fully impermeable to fluids such as blood. A cylindrical restrictor section 16, including an orifice with a diameter MD (see Fig. 5) also forms a part of blood regulation device 14, wherein cylindrical restrictor section 16 may have a length L.

[0058] In some embodiments, blood regulation element 14 may taper out downstream of the restrictor section at an angle 0 (see Fig. 3) which can range from 0 to 160°. In embodiments of the disclosure, Blood flow regulation device 10 may be designed so that the diameter MD of cylindrical restrictor section 16 of blood regulation element 14 is determined by angle 0 while 0 is determined by the diameter of the vessel into which blood flow regulation device 10 is inserted. If the vessel has a diameter DI, the restrictor section will have a diameter of MDI. If the vessel diameter is D2, the cylindrical restrictor section 16 will have a diameter MD2. When Di is larger than D2, MDI will be larger than MD2.e-filed RVMP-005 / 001WOSeptember 4, 2025 43730-02028

[0059] In some embodiments, blood flow regulation device 10 may be designed so that the relationship between the surface area ratios is substantially constant. In particular, the relationship between the surface area ratios may be described by the equation: SMDI\SDI+SI=SMD2\SD2+ S2=C, where: SMDI is the surface area of a cross section of cylindrical restrictor section 16 when blood flow regulation device 10 is positioned in a vessel including a diameter Di; SDI is the surface area of a cross section of blood flow regulation device 10 when blood flow regulation device 10 is positioned in a vessel with diameter of Di; 8i is a tolerance that is derived from the flexibility of the outer vs. inner frames and the inconsistencies in vessel (e.g. IVC) diameter since such vessels do not have consistent diameters; SMD2 is the surface area of a cross section of cylindrical restrictor section 16 when blood flow regulation device 10 is positioned in a vessel including a diameter D2; SD2 is the surface area of cross section of blood flow regulation device 10 when blood flow regulation device 10 is positioned in a vessel with diameter of D2; £2 is a tolerance that is derived from the flexibility of the outer vs. inner frames and the inconsistencies in vessel (e.g. IVC) diameter since such vessels do not have consistent diameters; and C is a constant.

[0060] Blood flow through blood flow regulation device 10 and into a body lumen (such as the Inferior Vena Cava (IVC) 26) which includes a larger diameter than the diameter MD of cylindrical restrictor section 16, creates a Venturi Effect (based on the Bernoulli Effect), in which the flow through cylindrical restrictor section 16 includes a lower pressure and higher velocity than blood flowing through an unrestricted vessel, which affects the pressure regime directly downstream of blood flow regulation device 10.

[0061] In practice, and according to some embodiments, blood flow regulation device 10 may be implanted in a body lumen such as the IVC for a predetermined period and then removed using snagging hook 11, which may be connected to outer frame 13 via a plurality of hook arms 12. Alternatively, blood flow regulation device 10 may be rigidly connected to a delivery system (not shown) and placed and removed using that delivery system.

[0062] In some embodiments, blood flow regulation device 10 expands radially until it is constrained by, for example, the inner wall of a blood vessel. Outer frame 13 may be tube shaped, substantially continuous in diameter and made from Nitinol. Outer frame 13 may be an open frame with no membrane or other covering. Outer frame 13 may be radiallye-filed RVMP-005 / 001WOSeptember 4, 2025 43730-02028 expandable such that it conforms to the diameter of the vessel in which it is placed. Outer frame 13 may have a substantially continuous diameter from its proximal to its distal end. In some embodiments, when placed in a blood vessel, blood flows from the proximal end of blood flow regulation device 10 to the distal end ofblood flow regulation device 10. When placed in a blood vessel, blood enters blood flow regulation device 10 through first flow opening 36 and flows through blood flow regulation device 10.

[0063] In some embodiments, blood flow regulation device 10 may include a blood regulation element 14 inside of outer frame 13. Blood regulation element 14 may include an inner frame 15, a conical section 32, a cylindrical restrictor section 16 and an outlet section 134. Blood regulation element 14 may be contained within outer frame 13, extend from the proximal end of outer frame 13 to the distal end of outer frame 13 and can be attached to the proximal and distal ends of outer frame 13 at connection points 18 with the proximal end of blood regulation element 14 being attached to the proximal end of outer frame 13 and the distal end ofblood regulation element 14 being attached to the distal end of outer frame 13. In some embodiments, outer frame 13 and blood regulation element 14 are only connected at their proximal and distal ends respectively with no intermediate connection points. Inner frame 15 may be contained within outer frame 13.

[0064] In some embodiments, outer frame 13 and inner frame 15 may be constructed of struts 30, and / or a mesh of struts 30. In some embodiments, outer frame 13 may be constructed to be less rigid than inner frame 15; specifically, the struts, which form outer frame 13, may be less rigid than the struts which form inner frame 15, and / or may be thinner than the struts which form inner frame 15.

[0065] In some embodiments, at least a portion of inner frame 15 may be covered by a membrane 22 to channel blood through at least a portion of blood regulation element 14. Membrane 22 may be used to create a blood flow channel within outer frame 13. In some embodiments, where membrane 22 does not cover all of inner frame 15, blood flowing through blood flow regulation device 10 may pass through the uncovered portions of inner frame 15 and into the space between blood regulation element 14 and outer frame 13.

[0066] In some embodiments, blood regulation element 14 may include a conical section 32, a cylindrical restrictor section 16 and an outlet section 134. A proximal end of conical section 32 may be connected to outer frame 13 at a proximal end of conical section 32, and a distal end of conical section 32 may be connected to a proximal end of cylindrical restrictore-filed RVMP-005 / 001WOSeptember 4, 2025 43730-02028 section 16. A distal end of cylindrical restrictor section 16 may be connected to a proximal end of outlet section 134. A distal end of outlet section 134 may be connected to a distal end of outer frame 13, and inner frame 15 may form conical section 32, cylindrical restrictor section 16 and outlet section 134.

[0067] In some embodiments, conical section 32 may taper from a first diameter at a proximal end of conical section 32 to a second diameter at a distal end of conical section 32. The first diameter may be greater than the second diameter, and the first diameter may be equal to the diameter of outer frame 13 at its proximal end. The second diameter may be equal to the diameter of the proximal end of cylindrical restrictor section 16. The diameter of conical section 32 may taper inward in a proximal to distal direction. The diameter of conical section 32 may taper in the direction of blood flow and may be covered by a membrane 22 to channel blood through blood regulation element 14 (and at least a portion of blood flow regulation device 10). Membrane 22 may be positioned on outer surface 40 of conical section 32.

[0068] In some embodiments, outer surface 40 of conical section 32 may form an angle a with central axis 20, which may decrease as the diameter of outer frame 13 decreases. Accordingly, the angle a may be smaller when blood flow regulation device 10 is positioned in vessels with smaller diameters and larger when blood flow regulation device 10 is positioned in vessels with a larger diameter.

[0069] In some embodiments, cylindrical restrictor section 16 may have a continuous diameter from its proximal to its distal end, and, in some embodiments, may be proportional to the diameter of outer frame 13. The diameter of cylindrical restrictor section 16 may be proportional to the diameter of the vessel in which blood flow regulation device 10 is positioned. Cylindrical restrictor section 16 may provide a restriction point to restrict the flow of blood through blood regulation element 14 and blood flow regulation device 10. Cylindrical restrictor section 16 may be covered by a membrane 22 (in some embodiments, the outer surface 42) to channel blood through cylindrical restrictor section 16. Blood flowing through cylindrical restrictor section 16 may have a higher velocity than blood flowing through conical section 32, and / or through outlet section 134 (and correspondingly, blood flowing into blood flow regulation device 10 may have a higher pressure than blood flowing out of blood flow regulation device 10). Blood upstream of blood flow regulation device 10 may have a higher pressure than blood downstream of blood flow regulatione-filed RVMP-005 / 001WOSeptember 4, 2025 43730-02028 device 10, and correspondingly, Blood flowing through cylindrical restrictor section 16 may have a higher pressure than blood flowing through outlet section 134.

[0070] In some embodiments, the diameter of cylindrical restrictor section 16 decreases as the diameter of blood flow regulation device 10 decreases, and outer surface 42 thereof may be substantially parallel to the outer surface 44 of blood flow regulation device 10. In some embodiments, outer surface 42 of cylindrical restrictor section 16, in minimum form, may remain substantially parallel to the outer surface 44 of blood flow regulation device 10 as the diameter of blood flow regulation device 10 increases or decreases. Moreover, the cross- sectional area of cylindrical restrictor section 16 may increase or decrease in direct proportion to increases or decreases in the cross-sectional area of outer frame 13. Similarly, in some embodiments, the diameter of cylindrical restrictor section 16 may increase or decrease in direct proportion to increases or decreases in the diameter of outer frame 13.

[0071] In some embodiments, outlet section 134 may taper from a first diameter at a proximal end to a second diameter at a distal end, where the first diameter may be smaller than the second diameter. Outlet section 134 may taper outward in a proximal to distal direction, and correspondingly, outlet section 134 may taper outward in a direction of blood flow. An outer surface 46 of outlet section 134 may form an angle 0 (with central axis 20), which may decrease as the diameter of blood flow regulation device 10 decreases and increase as the diameter of blood flow regulation device 10 increases.

[0072] In some embodiments, at least a portion of the lateral walls of outlet section 134 may be open, that is, the walls lack a membrane covering at least a portion of outer surface 46 of outlet section 134. In some embodiments, the pressure of blood entering outlet section 134 may drop below the pressure of blood in cylindrical restrictor section 16.

[0073] In some embodiments, blood in blood flow regulation device 10 may pass through outer surface 46 and into outer frame 13, and / or blood leaving cylindrical restrictor section 16 may drop in pressure as it enters outlet section 134.

[0074] In some embodiments, a method is provided for controlling the flow of blood through a blood flow regulation device 10. The method may include modifying the diameter of cylindrical restrictor section 16 to restrict the flow of blood through blood regulation element 14 and thereby, through the blood flow regulation device 10. The method may also include modifying the cross-sectional area of cylindrical restrictor section 16 to restrict thee-filed RVMP-005 / 001WOSeptember 4, 2025 43730-02028 flow of blood through blood regulation element 14 and blood flow regulation device 10. The method may also include changing the diameter or cross- sectional area of cylindrical restrictor section 16 proportionately to changes in the diameter or cross-sectional area of outer frame 13.

[0075] In some embodiments, the method further includes increasing the diameter or cross- sectional area of cylindrical restrictor section 16 in response to increases in the diameter or cross-sectional area of outer frame 13, which can occur when blood flow regulation device 10 is placed in a blood vessel (e.g., inferior vena cava 26). The method may also include extending the length inner frame by decreasing the diameter of outer frame 13, and / or increasing the length of restrictor section (also by decreasing the diameter of outer frame 13). In some embodiments, the method may also include decreasing the length of cylindrical restrictor section 16 by increasing the diameter of outer frame 13.

[0076] In some embodiments, the method may also include positioning blood flow regulation device 10 in a blood vessel such as inferior vena cava 26 and channeling blood through blood regulation element 14. Specifically, channeling blood through the blood regulation element 14 includes channeling the blood into conical section 32 and cylindrical restrictor section 16, which, in some embodiments, confines the blood in blood regulation element 14 until the blood leaves cylindrical restrictor section 16. In some embodiments, the method may also include restricting the flow of blood through the vessel by decreasing the diameter or cross-section of cylindrical restrictor section 16.

[0077] In some embodiments, methods are provided to decrease the pressure of blood in one section of a blood vessel (e.g., the IVC) by placing a blood flow regulation device 10 in the blood vessel and decreasing the pressure of the blood flow as it leaves a blood regulation element 14 as compared with the pressure of blood entering blood flow regulation element 14. In some embodiments, the method may further include one and or another of the following steps, functions, and / or clarifications (if not mutually exclusive): decreasing the pressure of blood leaving cylindrical restrictor section 16 when compared to the pressure of blood entering blood flow regulation device 10; increasing the velocity of blood as it flows through conical section 32; maintaining the velocity of blood substantially constant as it flows through cylindrical restrictor section 16;e-filed RVMP-005 / 001WOSeptember 4, 2025 43730-02028 decreasing the velocity of blood as it flows into outlet section 134 and out the distal end of blood flow regulation device 10; increasing the pressure of blood as it flows through conical section 32; maintaining the pressure of blood substantially constant as it flows through cylindrical restrictor section 16; and decreasing the pressure of blood as it flows into outlet section 134 and out the distal end of blood flow regulation device 10.

[0078] In some embodiments, the method may include controlling the flow of blood through a blood flow regulation device 10 placed in a blood vessel by channeling the blood through a blood regulation element 14 including a conical section 32, a cylindrical restrictor section 16 and an outlet section. In some embodiments, the method may further include one and or another of the following steps, functions, and / or clarifications (if not mutually exclusive): channeling the blood through a conical section 32 which tapers in the direction of blood flow; channeling the blood through a conical section 32 which tapers in a proximal to distal direction; increasing the pressure of the blood as it passes through a conical section 32; increasing the speed of blood flow as the blood passes through the conical section 32; channeling blood through a cylindrical restrictor section 16; maintaining the pressure of the blood at a substantially constant value as it travels through the cylindrical restrictor section 16; and maintaining the speed of the blood at a substantially constant value as it passes through the cylindrical restrictor section 16; placing a blood flow regulation device 10 in a blood vessel and restricting the flow of blood through the blood regulation device to between 1% and 5% of the blood flow through the vessel when it is unobstructed; decreasing the pressure of blood leaving the restricted section by 5mm Hg frome-filed RVMP-005 / 001WOSeptember 4, 2025 43730-02028 the pressure of blood entering the blood regulation device; restricting the diameter or cross section of the cylindrical restrictor section 16 to between 70 and 80 percent of the diameter of the vessel in which the blood flow regulation device 10 is placed; restricting the diameter or cross section of the cylindrical restrictor section 16 to approximately 70 percent of the diameter of the vessel in which the blood flow regulation device 10 is placed; conforming the diameter or cross-section of the cylindrical restrictor section 16 by applying pressure to the outer surface 44 of the blood flow regulation device 10, by, for example placing the blood flow regulation device 10 in a blood vessel; reducing the speed and pressure of blood as it exits the cylindrical restrictor section 16 and enters outlet section 134; releasing the blood exiting the cylindrical restrictor section 16 into the space between the blood regulation element 14 and the outer frame 13; and allowing blood to pass through the outer surface 46 of the outlet section 134 and into the space between the blood regulation element 14 and the outer frame 13.

[0079] In the embodiment illustrated in Fig. 14, blood flow regulation system 100 may include catheter 21 and blood flow regulation device 10. Blood flow regulation device 10 extends from catheter lumen 23 of catheter 21. In the embodiments illustrated herein, blood flow regulation device 10 may be one component of a blood flow regulation system 100, which may also include, for example, catheter 21. Blood flow regulation device 10 may include a conical section 32, a cylindrical restrictor section 16 and a cylindrical section 34. Blood flow regulation device 10 may include a frame 19 and a membrane 22, which membrane may be impervious to blood. Frame 19 may comprise outer frame 13 and second flow opening frame 17 and be constructed of struts 30, which may be, for example nitinol. Membrane 22 guides blood through blood flow regulation device 10, from cylindrical section 34 through conical section 32 and into cylindrical restrictor section 16.. Arrows 24 illustrated the direction of blood flow through blood flow regulation device 10. Cylindrical section 34 is designed to fit in a blood vessel such that frame 19, when expanded, is tight against the wall of the blood vessel holding blood flow regulation device 10 in place. Withe-filed RVMP-005 / 001WOSeptember 4, 2025 43730-02028 blood flow regulation device 10 in place the amount of blood which can bypass blood flow regulation device 10 is limited by cylindrical section 34 seal against the vessel wall. Blood enters blood flow regulation device 10 and cylindrical section 34 and through first flow opening 36. Blood passing through cylindrical section 34 enters conical section 32 which tapers to cylindrical restrictor section 16. Blood entering cylindrical restrictor section 16 will have a lower pressure and velocity than blood exiting cylindrical restrictor section 16. Blood exits blood flow regulation device 10 and cylindrical restrictor section 16 through second flow opening 38. In Fig. 14, second flow opening 38 is an oval shaped opening which extends proximally to distally along one side of cylindrical restrictor section 16. In embodiments of the invention cylindrical section 34 may include one or more second flow openings 38 arranged radially around cylindrical restrictor section 16.

[0080] In Fig. 15, a proximal end of cylindrical restrictor section 16 is disposed within catheter lumen 23 and a distal end of cylindrical restrictor section 16 is disposed outside of catheter lumen 23. As blood flow regulation device 10 is pulled into catheter lumen 23, cylindrical restrictor section 16 folds to fit into catheter lumen 23. As cylindrical restrictor section 16 folds, and second flow opening 38 collapses and is covered by the distal end of catheter 21, the size of second flow opening 38 is reduced, limiting the amount of blood which can pass through blood flow regulation device 10 and increasing the velocity and decreasing the pressure the of blood distal to second flow opening 38 and blood flow regulation device 10. Thus, the blood flow, blood velocity and blood pressure downstream of blood flow regulation device 10 may be controlled by moving second flow opening 38 into and out of catheter lumen 23. The oblong shape of second flow opening 38 assists in ensuring that in some embodiments blood flow decreases substantially linearly as second flow opening 38 is pulled into catheter lumen 23. Second flow opening frame 17 ensures that at least a portion of second flow opening 38 remains open as blood flow regulation device 10 is pulled into catheter 21. Membrane 22, supported by frame 19 (which may be constructed of struts 22) guides blood flow through blood flow regulation device 10 from first flow opening 36 to second flow opening 38, as illustrated by arrows 24.

[0081] Fig. 16 illustrates the blood regulation device 10 of Figs. 14 and 15 positioned in inferior vena cava 26. As illustrated by arrows 24, blood flows into first flow opening 36, through cylindrical section 34, conical section 32 and cylindrical restrictor section 16 and out second flow opening 38. By restricting the flow of blood, the pressure down stream ofe-filed RVMP-005 / 001WOSeptember 4, 2025 43730-02028 blood flow regulation device 10 is reduced at the intersections of renal veins 28 and inferior vena cava 26. Blood flow regulation device 10 may be deployed from catheter lumen 23 of catheter 21 such that blood flowing into first flow opening 36 is held within blood flow regulation device 10 by membrane 22 until it flows out second flow opening 38 as illustrated by arrows 24. Second flow opening 38 may be surrounded by second flow opening frame 17.

[0082] In the embodiments of the invention illustrated in Figs. 14 to 16, Blood flow regulation device 10 may be expandable such that, as it is moved from a first position within catheter lumen 23 to a second position external to catheter lumen 23 but within a blood vessel of a patient (such as, for example, the inferior vena cava IVC), blood flow regulation device 10 expands until the outer walls of cylindrical section 34 contact the inner walls of the blood vessel. In these embodiments blood flow regulation device 10 may include: frame 19, which is substantially covered by membrane 22; first flow opening 36; cylindrical section 34; conical section 32, and cylindrical restrictor section 16. First flow opening 36 may be an opening at the distal end of cylindrical section 34 which has a diameter substantially equal to the diameter of the blood vessel in which blood flow regulation device 10 is positioned. Conical section 32 may include membrane 22, which covers the external portion of frame 19 which forms conical section 32. The outer walls of cylindrical section 34 may expand to engage the inner walls of the blood vessel such that membrane 22 forms a seal against the inner walls of the blood vessel and blood flow regulation device 10 is held in place by the engagement of cylindrical section 34 with the inner walls of the blood vessel.

[0083] Cylindrical restrictor section 16 may be covered by membrane 22 such that blood flowing out of the proximal end of conical section 32 is guided into the distal end of cylindrical restrictor section 16. Conical section 32 may taper from a first diameter at a junction with the proximal end of cylindrical section 34 to a second, smaller, diameter at a distal end of cylindrical restrictor section 16. Cylindrical section 34 and conical section 32 are substantially covered by membrane 22, which extends from the distal end of cylindrical section 34 to the proximal end of conical section 32. Second flow openings 38 are openings in the portion of membrane 22 which surrounds cylindrical restrictor section 32.

[0084] In the embodiments of the invention illustrated in Figs. 14 to 16, blood flow regulation system 100 may be used to direct the flow of blood through a blood flow regulation device 10 wherein catheter 21 is inserted into, for example, the IVC of a patiente-filed RVMP-005 / 001WOSeptember 4, 2025 43730-02028 with blood flow regulation device 10 disposed within catheter lumen 23. Once catheter 21 is in place, Blood flow regulation device 10 may then be extended from the distal end of catheter 21 and into the IVC. As blood flow regulation device 10 is deployed cylindrical section 34 expands until it contacts the inner wall of the IVC with and outer wall of cylindrical section 34 engaging the inner wall of the IVC to hold blood flow regulation device 10 in position in the IVC. The portion of membrane 22 covering cylindrical section 34 may form a seal with the inner wall of the IVC such that substantially all of the blood flowing through the IVC will flow into cylindrical section 34 through first flow opening 36. Blood will then flow into first flow opening 36, through cylindrical section 34, conical section 32, and into cylindrical restrictor section 16 and exit blood flow regulation device 10 through one or more second flow openings 38. The flow of blood out of second flow openings 38 may be controlled by moving cylindrical restrictor section 16 of blood flow regulation device 10 into and out of catheter lumen 23. As cylindrical restrictor section 16 is moved into and out of catheter lumen 23, distal end 25 of catheter 21 may be used to cover second flow openings 38, thus closing proximal portions of second flow openings 38. Once all of second flow openings 38 have been pulled past distal end 25 of catheter 21 and into catheter lumen 23, the flow of blood through blood flow regulation device 10 will cease. Thus, the flow of blood through blood flow regulation device 10 may be controlled or regulated by appropriately positioning second flow openings 38 in catheter lumen 23. The pressure of blood in the vena cava proximal to blood flow regulation device 10 may also be controlled or regulated by appropriately positioning second flow openings 38 in catheter lumen 23.

[0085] Fig. 17 illustrates an alternative blood flow regulation device 10 which is collapsible into a two-part catheter 21. In this embodiment, blood flow regulation device 10 may include flow control section 78, central section 80 and distal section 82. In embodiments of the invention, central section 80 may be a cylindrical section such as cylindrical section 34. In embodiments of the invention, distal section 82 may be a conical section such as conical section 32. Catheter 21 may include a proximal catheter section 54, a distal catheter section 56 and a traumatic catheter tip 52. Catheter 21 may further include guidewire 50. When blood flow regulation device 10 is delivered into the inferior vena cava, proximal catheter section 54 and distal catheter section 56 are joined and blood flow regulation device 10 is collapsed within catheter lumen 23 of catheter 21. Blood flow regulation device 10 may be delivered by separating proximal catheter section 54 and distal catheter section 56, allowinge-filed RVMP-005 / 001WOSeptember 4, 2025 43730-02028 blood flow regulation device 10 to expand into the vessel. In this embodiment, blood flow regulation device 10 may have first flow opening 36, an outer frame 13, a membrane 22, one or more foldable protrusions 60 and second flow opening 38. The position of foldable protrusion 60 and the size of second flow opening 38 may be controlled by the movement of one or more control wires 74 which may be connected to an internal or external handle or controller (see, e.g., W02020 / 121309A1, herein incorporated by reference in its entirety). In the embodiment of Fig. 17, control wires 74 extend from foldable protrusions 60, through guidewire lumen 58 and into proximal catheter section 54. Arrows 24 illustrate the direction of blood flow into and out of blood flow regulation device 10.

[0086] In the embodiment of the invention illustrated in Fig. 17 a blood flow regulation system 100 includes a catheter 23, a blood flow delivery device 10, a guide wire 50 and control wires 74. Catheter 21 may include a proximal section 54 and a distal catheter section 56 which may be separable. Distal catheter section 56 may include a catheter tip 52 which may be designed to be atraumatic. Blood flow regulation device 10 may include a distal section 82, a central section 80 and a flow control section 78. Distal section 82 may include first flow opening 36, substantially all of distal section 82 may be open to the flow of blood (i.e., not covered by membrane 22). Central section 80 may be expandable to contact the inner walls of a vein in which blood flow regulation device 10 is positioned. Flow control section 78 may include foldable protrusions 60, which may be used to control the flow of blood through blood flow regulation device 10. Blood flow regulation device 10 may be collapsible to fit within catheter lumen 23 of catheter 21. Blood flow regulation device 10 may be deployed by separating proximal section 54 and distal catheter section 56 of catheter 21. Blood flow regulation device 10 may further include an outer frame 13 which may be covered at least in part by membrane 22. Membrane 22 may cover a proximal portion of blood flow regulation device 10, including portions of foldable protrusions 60, which may be inwardly foldable. Guide wire 50 may run through a lumen in proximal section 54, through blood flow regulation device 10 and into distal catheter section 56 and may be used to separate or bring together proximal section 54 and distal section 56. Control wires 74 may extend through a lumen in proximal section 54 and out to foldable protrusions 60 such that movement of foldable protrusions 60 may be controlled by movement of control wires 74.

[0087] In the embodiment of the invention illustrated in Fig. 17 blood flow through ae-filed RVMP-005 / 001WOSeptember 4, 2025 43730-02028 vessel, such as an IVC, may be regulated by poisoning catheter 21 within the IVC and separating proximal section 54 from distal catheter section 56 to release blood flow regulation device 10. Separation of proximal section 54 from distal catheter section 56 results in the expansion of blood flow regulation device 10 into the IVC. As blood flow regulation device 10 expands, central section 80 expands to a diameter substantially equal to the diameter of the IVC and outer frame 13 exerts pressure against an inner wall of the IVC, holding blood flow regulation system 100 and blood flow regulation device 10 in position within the IVC. Blood may then flow into first flow opening 36, through central section 80, through flow control section 78 and out second flow opening 38. Blood flow through blood flow regulation device 10 may then be controlled using foldable protrusions 60, which may be folded by moving control wires 74. Blood flow regulation device 10 may be removed from the IVC by joining the two halves of catheter 21, thus collapsing blood flow regulation device 10 into catheter lumen 23 and then removing catheter 21.

[0088] Fig. 18 illustrates a view of an alternative embodiment of blood flow regulation device 10 including first flow opening 36, frame 19, membrane 22, guidewire lumen 58 and second flow opening 38. In the embodiment of Fig. 18, second flow opening 38 is positioned proximally to first flow opening 36 and adjacent to guide wire lumen 58. In this embodiment, struts 30, forming frame 19 may be affixed to guide wire lumen 58 with membrane 22 covering a portion of frame 19 extending from second flow opening 38 to first flow opening 36. In this embodiment, first flow opening 36 and second flow opening 38 may be fixed in diameter when blood flow regulation device 10 is fully extended from catheter 21.

[0089] Fig. 19 illustrates a view of an alternative embodiment of blood flow regulation device 10 including first flow opening 36, frame 19, membrane 22, guidewire lumen 58 and second flow opening 38. In the embodiment of Fig. 18, first flow opening 36 is positioned proximally to second flow opening 38 and adjacent to guide wire lumen 58. In this embodiment, struts 30, forming frame 19, may be affixed to guide wire lumen 58 with membrane 22 covering a portion of frame 19 extending from first flow opening 36 to second flow opening 38. In this embodiment, first flow opening 36 and second flow opening 38 may be fixed in diameter when blood flow regulation device 10 is fully extended from catheter 21.

[0090] Fig. 20 illustrates the blood flow regulation device 10 of Fig. 18 with the additione-filed RVMP-005 / 001WOSeptember 4, 2025 43730-02028 of blood flow regulator 70, which, in the embodiment of Fig. 20 may be a balloon 62. As illustrated in Fig. 20, balloon 62 may be positioned and sized to control the flow of blood through second flow opening 38 of blood flow regulation device 10. As illustrated in Fig. 20, as balloon 62 is moved towards second flow opening 38 blood is forced to flow around balloon 62 and between balloon 62 and the inner diameter of second flow opening 38, which is formed by membrane 22. The flow of blood through second flow opening 38 may thus be restricted by moving balloon 62 into second flow opening 38. In addition to controlling the flow of blood through second flow opening 38 by appropriately positioning balloon 62 (see dotted rendition of balloon 62 in Fig. 22), the flow of blood through second flow opening 38 may be further regulated by inflating or deflating balloon 62. In this embodiment, guide wire 50 may pass through an opening in balloon 62 and balloon 62 may be attached to guide wire 50 proximal to catheter tip 52. As illustrated in Figs. 20 and 22, blood flow regulator 70 may comprise bi-conal element 64. Bi-conal element 64 may include a catheter tip 52, which may be an atraumatic catheter tip, at a first, distal end and a flow regulation element 67 at a second, proximal end. In this embodiment, flow regulation element 67 may be a cone shaped element.

[0091] As illustrated in Fig. 23, as biconal element 64 is moved toward second flow opening 38, blood flow passes between flow regulation element 67 and membrane 22, restricting the flow of blood (see arrows 24) through second flow opening 38. Thus, the flow of blood through blood flow regulation device 10 into first flow opening 36 and out of second flow opening 38 may be controlled by moving flow regulation element 67 of blood flow regulator 70 into and out of second flow opening 38. The position of blood flow regulator 70 may be controlled using guidewire 50. Guidewire 50 may be used to control the flow of blood through second flow opening 38 and, thus, the flow of blood through blood flow regulation device 10. Blood flow is regulated by appropriately positioning blood flow regulator 70 and flow regulation element 67 in second flow opening 38. In the schematic illustration of Fig. 23, the flow of blood (represented by arrows 24) may be seen as blood flow regulator 70, including flow regulation element 67, is moved into second flow opening 38 (see dotted line illustration of blood flow regulator 70).

[0092] Figs. 24A and 24B illustrate alternative embodiments of blood flow regulator 70. In Fig. 24A, blood flow regulator 70 includes a catheter tip 52 and a flow regulation element 67. In Fig. 24B, a catheter tip 52 and a flow regulation element 67 of blood flow regulatore-filed RVMP-005 / 001WOSeptember 4, 2025 43730-0202870 are separated by a central element 76. The position of blood flow regulator 70 may be controlled by guidewire 50.

[0093] In the embodiment of the invention illustrated in Figs. 18, 20 and 22, blood flow regulation system 100 includes catheter 21, guidewire 50 and blood flow regulation device 10. Blood flow regulation device 10 may include frame 19, membrane 22, conical section 32, cylindrical section 34 and blood flow regulator 70. Frame 19 may be connected to a guidewire lumen 58. Membrane 22 may cover at least a portion of frame 19 between a first flow opening 36 and a second flow opening 38.

[0094] In the embodiment of Figs. 20 and 22, blood flow regulation device 10 may include conical section 32 and cylindrical section 34. Cylindrical section 34 may be designed to engage an inner surface of a vein, such as the IVC, when blood flow regulation device 10 is fully deployed within the vein. First flow opening 36 may be positioned at a distal end of cylindrical section 34. Conical section 32 may include second flow opening 38 at a proximal end of conical section 32. Second flow opening 38 may be a substantially circular opening in membrane 22. Blood flow regulator 70 may be a biconal element 64 which may be affixed to guide wire 50. Bi-conal element 64 may be affixed to a distal end of guide wire 50. Biconal element 64 may include a catheter tip 52 at a distal end of biconal element 64, which catheter tip may be atraumatic and may be conical in shape. Bi-conal element 64 may further include a flow regulation element 67 at a proximal end of biconal element 64, which may be conical in shape. In embodiments of the invention, blood flow regulator 70 may further include a central element 76 separating catheter tip 52 and flow regulation element 67, which central element 76 may be conical in shape. In a further embodiment of the invention, blood flow regulator 70 may be a balloon 62. Balloon 62 may be affixed to a distal end of guidewire 50. Alternatively, guidewire 50 may pass through balloon 62.

[0095] In the embodiment of the inventions illustrated in Figs. 20 and 22 blood flow may be regulated using a blood flow regulation system 100 as described above. In particular, blood may be regulated by positioning blood flow regulation device 10 in a vein, such as, for example, the IVC by extending blood flow regulation device 10 from the distal end of a catheter 21 and expanding blood flow regulation device 10 into the IVC until outer portion of cylindrical section 34 touches the interior walls of the IVC. In particular, membrane 22 on cylindrical section 34 touches the interior walls of the IVC such that membrane 22 forms a seal against the inner wall of the IVC. With blood flow regulation device 10 deployed,e-filed RVMP-005 / 001WOSeptember 4, 2025 43730-02028 blood in the IVC enters cylindrical section 34 through first flow opening 36 and passes through cylindrical section 34 to conical section 32 and out of blood flow regulation device 10 through second flow opening 38. Blood flow through second flow opening 38 may be regulated using blood flow regulator 70. Blood flow regulator 70 may be positioned in or close to second flow opening 38 such that the presence of blood flow regulator 70 restricts the flow of blood through second flow opening 38. Blood flow regulator 70 may be positioned using guide wire 50. Blood flow regulator 70 may any suitable element, including a balloon or a bi-conal element. Blood flow regulator 70 may operate by forcing blood to flow between an outer surface of blood flow regulator 70 and second flow opening 38. Blood flow regulator 70 may operate by forcing blood to flow between an outer surface of blood flow regulator 70 and membrane 22 which forms second flow opening 38.

[0096] In Fig. 25, blood flow regulator 70 comprises balloon 62 which may be positioned distal to second flow opening 38 of blood flow regulation device 10. In embodiments of the invention balloon 62 may be positioned upstream from second flow opening 38 when blood flow regulation device 10 is positioned in a blood vessel. In this embodiment, balloon 62 may be pulled into second flow opening 38 to regulate the flow of blood through second flow opening 38 and blood flow regulation device 10. Guidewire 50 may extend through balloon 62. In embodiments of the invention balloon 62 may be affixed to guidewire 50 proximal to catheter tip 52 such that balloon 62 is poisoned in first flow opening 38 by moving guide wire 52. Blood flow regulation device 10 may be affixed to or extend from guidewire lumen 58 and include first flow opening 36 and membrane 22.

[0097] In the embodiment of Fig. 25, both the positioning and inflation of balloon 62 may be used to control the flow of blood through second flow opening 38. In the embodiment of Fig. 25 blood enters blood flow regulation device 10 through second flow opening 38 and exits blood flow regulation device 10 through first flow opening 36. In this embodiment, second flow opening 38 may be referred to as an inlet opening or a distal flow opening. In particular, as balloon 62 is pulled into second flow opening 38, second flow opening 38 becomes occluded by the presence of balloon 62. The degree of occlusion resulting from the presence of balloon 62 may be moderated by the degree of inflation of balloon 62, in particular, by inflating balloon 62 when it is at least partially within second flow opening 38, second flow opening 38 may be at least partially occluded and the amount of blood passing through second flow opening 38 and blood flow regulation device 10 may bee-filed RVMP-005 / 001WOSeptember 4, 2025 43730-02028 restricted.

[0098] In Fig. 26, blood flow regulator 70 may comprise a biconal element 64 which may be positioned distal to second flow opening 38 of blood flow regulation device 10. In embodiments of the invention blood flow regulator 70 may be positioned upstream of second flow opening when second flow opening is positioned in a blood vessel. Bi-conal element 64 may include flow regulation element 67 at a proximal end and catheter tip 52 at a distal end. In this embodiment, bi-conal element 62 may be pulled into second flow opening 38 to regulate the flow of blood through second flow opening 38 and blood flow regulation device 10. In this embodiment, flow regulation element 67 may be pulled into second flow opening 38 to regulate the flow of blood through second flow opening 38 and blood flow regulation device 10. Guidewire 50 may be attached to a proximal end of bi- conal element 64. In embodiments of the invention biconal element 64 may be affixed to a distal end of guidewire 50. In embodiments of the invention, a proximal end of biconal element 64 is poisoned in first flow opening 38 by moving guide wire 52. In embodiments of the invention flow regulation element 67 of biconal element 64 may be affixed to guidewire 50 proximal to catheter tip 52 such that flow regulation element 67 is poisoned in first flow opening 38 by moving guide wire 52. In embodiments of the invention, blood flow regulator 70 may have a diameter of DBE. In embodiments of the invention DBE may be the diameter of a central portion of bi-conal element 64. In embodiments of the invention DBE may be the diameter of a distal end of flow regulation element 67.

[0099] In the embodiment of Fig. 26, the positioning of blood flow regulator 70 may be used to control the flow of blood through second flow opening 38. In particular, as blood flow regulator 70 is pulled into second flow opening 38, second flow opening 38 becomes occluded by the presence of flow regulation element 67. The degree of occlusion resulting from the presence of blood flow regulator 70 may be moderated by the diameter DBE and the position of flow regulation element 67. Diameter DBE may be equal to, greater than or less than the diameter of second flow opening 38. In embodiments of the invention, a diameter DBE of greater than or equal to the diameter of second flow opening 38 would result in a blood flow regulation device 10 wherein the flow of blood through blood flow regulation device 10 may be fully occluded by positioning blood flow regulator 70 within second flow opening 38. In embodiments of the invention a diameter DBE of less than the diameter of second flow opening 38 would ensure that the flow of blood through blood flowe-filed RVMP-005 / 001WOSeptember 4, 2025 43730-02028 regulation device 10 is never fully occluded.

[0100] Fig 27 illustrates how the positioning of blood flow regulator 70 regulates the flow of blood through blood flow regulation device 10. In the schematic illustration of Fig. 27, as blood flow regulator 70 is pulled into second flow opening 38 (as illustrated by the dotted outline of blood flow regulator 70) the area of second flow opening 38 blocked by flow regulation element 67 is increased, reducing the flow of blood through second flow opening 38 and, thus, through blood flow regulator 70. Fig. 24B illustrates an alternate embodiment of blood flow regulator 70 which may be used in place of the blood flow regulator 70 illustrated in Figs. 26 and 27.

[0101] In the embodiment of the inventions illustrated in Figs. 25 and 26 blood flow may be regulated using a blood flow regulation system 100 as described above. In particular, blood may be regulated by positioning blood flow regulation device 10 in a vein, such as, for example, the IVC by extending blood flow regulation device 10 from the distal end of a catheter 21 and expanding blood flow regulation device 10 into the IVC until outer portion of cylindrical section 34 touches the interior walls of the IVC. In particular, membrane 22 on cylindrical section 34 touches the interior walls of the IVC such that membrane 22 forms a seal against the inner wall of the IVC. With blood flow regulation device 10 deployed, blood in the IVC enters conical section 32 through second flow opening 38 and passes through conical section 32 to cylindrical section 34 and out of blood flow regulation device 10 through first flow opening 38. Blood flow through second flow opening 38 may be regulated using blood flow regulator 70. Blood flow regulator 70 may be positioned in or close to second flow opening 38 such that the presence of blood flow regulator 70 restricts the flow of blood through second flow opening 38. Blood flow regulator 70 may be positioned using guide wire 50. Blood flow regulator 70 may any suitable element, including a balloon or a bi-conal element. Blood flow regulator 70 may operate by forcing blood to flow between an outer surface of blood flow regulator 70 and second flow opening 38. Blood flow regulator 70 may operate by forcing blood to flow between an outer surface of blood flow regulator 70 and membrane 22 which forms second flow opening 38.

[0102] In the embodiment of Figs. 25 and 26, blood flow regulation device 10 may include conical section 32 and cylindrical section 34. Cylindrical section 34 may be designed to engage an inner surface of a vein, such as the IVC, when blood flow regulation device 10 is fully deployed within the vein. First flow opening 36 may be positioned at a proximal ende-filed RVMP-005 / 001WOSeptember 4, 2025 43730-02028 of cylindrical section 34. Cylindrical section 34 may include second flow opening 38 at a distal end of cylindrical section 34.

[0103] Fig. 28 illustrates a blood flow regulation device 10 including membrane 22 covering at least a portion of frame 19, which is made up of struts 30 and includes flow openings 72. As illustrated by arrows 24, blood flows into first flow opening 36, through blood flow regulation device 10 and out through flow openings 72. In embodiments of the invention multiple flow openings 72 may form a second flow opening such as second flow opening 38. In Fig. 28 blood flow regulation device 10 is in its open state following release from catheter 21 and blood flow through blood flow regulation device 10 is not restricted or is minimally restricted. In this embodiment, guide wire 50 extends through blood flow regulation device 10 to atraumatic catheter tip 52. In the embodiment of Fig. 28, blood flow regulation device 10 may further include conical section 32 and cylindrical section 34. In embodiments of the invention flow openings 72 may be positioned in conical section 32.

[0104] In Fig. 29 blood flow regulation device 10 is being pulled back into catheter lumen 23 of catheter 21 in a controlled manner. As blood flow regulation device 10 is pulled into catheter lumen 23, flow openings 72 located near the proximal end of blood flow regulation device 10 shrink, forming slots through which blood exits blood flow regulation device 10. As the size of flow openings 72 shrink, the flow of blood out of blood flow regulation device 10 is impeded. In Fig. 29, flow openings 72 are reduced to slits by the crimping effect of pulling blood flow regulation device 10 into catheter 21. The degree of crimping controls blood flow and therefore the pressure gradient over the device. The distal end 25 of catheter 21 limits the length of flow openings 72 as blood flow regulation device 10 is pulled into catheter lumen 23.

[0105] In embodiments of the invention, conical section 32 may have a substantially conical shape, tapering from a first, larger diameter to a second, smaller diameter, where the first larger diameter may be substantially equal to a diameter of cylindrical section 34 and the second, smaller, diameter may be substantially equal to a diameter of catheter lumen 23. In embodiments of the invention, conical section 32 may be an inlet section. In embodiments of the invention, conical section 32 may be an outlet section. In embodiments of the invention all or a portion of conical section 32 may be covered by membrane 22. In embodiments of the invention the portion of conical section 32 covered by membrane 22 may restrict the flow of blood as it passes through conical section 32. In embodiments ofe-filed RVMP-005 / 001WOSeptember 4, 2025 43730-02028 the invention conical section 32 may be referred to as a restrictor section. In embodiments of the invention, second

[0106] In embodiments of the invention, cylindrical section 34 may have a substantially cylindrical shape, with a diameter that is substantially the same from its proximal to its distal end. In embodiments of the invention, conical section 32 may be an inlet section. In embodiments of the invention, conical section 32 may be an outlet section. In embodiments of the invention, cylindrical section 34 may expand within a body lumen (e.g., a blood vessel or vein) until the outer surface of cylindrical section 34 contacts the inner surface of the body lumen. In embodiments of the invention cylindrical section 34 may engage the inner surface of the body lumen, anchoring blood flow regulation device 10 in place. In embodiments of the invention, the pressure exerted by the expansion of blood flow regulation device 10 on an inner surface of a body lumen may anchor the blood flow regulation device in place.

[0107] In embodiments of the invention, blood flow regulation system 100 may include a first pressure sensor 110 which may be positioned on an element of blood flow regulation system 100 distal to blood flow regulation device 10. In embodiments of the invention, blood flow regulation system 100 may include a second pressure sensor 120 which may be positioned on an element of blood flow regulation system 100 proximal to blood flow regulation device 10. In embodiments of the invention, first pressure sensor 110 may be positioned on catheter tip 52. In some embodiments, the second pressure sensor 120 may be positioned on catheter 21. The pressure sensors 110 and 120 can be any appropriate pressure measuring device familiar to one of skill in the art, including a port to a pressure sensor provided for in a handle of device and system embodiments of the disclosure.

[0108] Incorporated herein by reference are the disclosures of each of W02017 / 081561A1, W02020 / 121309A1, and WO2024 / 121817A1, in in their entireties. The structure, systems, methods, devices, and portions thereof can also be variously combined with the embodiments and elements described above to establish even more embodiments for the present disclosure. For example, some embodiments of the present disclosure can include a handle (e.g., a control handle) for operating the blood regulation device (and / or other components of various embodiments); see, e.g., W02020 / 121309A1, Figs. 3-4 and 10 thereof pertaining to handle 30 (as well as elements and components thereof) and associated written description.e-filed RVMP-005 / 001WOSeptember 4, 2025 43730-02028Examples according to some embodiments of the disclosure:Example 1: A blood flow regulation device including an outer frame surrounding a central axis, a blood regulation element positioned in the outer frame, the blood regulation element including an inner frame positioned within the outer frame and only connected to the outer frame at proximal and distal ends of the outer frame, such that a proximal end of the inner frame is connected to a proximal end of the outer frame, and a distal end of the inner frame is connected to a distal end of the outer frame, and a membrane arranged to cover at least a portion of the inner frame, and a central axis running through a center of at least one of the outer frame and the blood regulation element.Example !: The device of example 1, where the outer frame is tubular and includes a diameter which is substantially continuous from the proximal end to the distal end.Example 3: The device of examples 1 or 2, where no portion of the outer frame is covered by a membrane.Example 4: The device of any of examples 1-3, where the blood flow regulation device is radially expandable.Example 5: The device of any of examples 1-4, where the blood blow regulation device radially expands to conform to a diameter of a vessel in which it is placed.Example 6: The device of any of examples 1-5, where the outer frame comprises a wire mesh.Example 7: The device of example 6, where the wire mesh comprises Nitinol struts.Example 8: The device of any of examples 1-7, where the membrane creates a fluid channel through the blood regulation element.Example 9: The device of any of examples 1-8, where fluid exiting the blood flow regulation device flows into the space between the inner and outer frames.Example 10: The device of any of examples 1-9, where the inner frame floats with respect to the outer frame between the proximal and distal ends of the outer frame.Example 11: The device of any of examples 1-10, where the length of the blood flow regulation device decreases as the diameter of the outer frame increases.Example 12: The device of any of examples 1-11, where the inner frame is more rigid thane-filed RVMP-005 / 001WOSeptember 4, 2025 43730-02028 the outer frame.Example 13: The device of any of examples 1-12, where the inner frame and the outer frame comprise Nitinol struts, the struts of the inner frame being more rigid than the struts of the outer frame.Example 14: The device of example 13, where the struts of the inner frame are thicker than the struts of the outer frame.Example 15: The device of any of examples 1-14, where the blood regulation element includes an inlet section including a proximal end attached to the proximal end of the outer frame; a restrictor section including a proximal end attached to a distal end of the inlet section, and an outlet section including a proximal end attached to a distal end of the restrictor section and including a distal end attached to the distal end of the outer frame, and the membrane covers at least one of and preferably both of the inlet section and the restrictor section.Example 16: The device of any of examples 1-15, where in the blood regulation element includes a substantially hourglass shape.Example 17: The device of any of examples 1-16, where the inlet section tapers from a first diameter at its proximal end to a second, smaller, diameter at its distal end.Example 18: The device of any of examples 15-17, where an outer surface of the inlet section forms an angle a with the central axis where angel a decreases as the diameter of the blood flow regulation device decreases.Example 19: The device of any of examples 15-18, where the restrictor section has a continuous diameter from its proximal to its distal end.Example 20: The device of any of examples 15-19, where the diameter of the restrictor section is proportional to the diameter of the outer frame; the diameter of the outer frame decreases as the diameter of the outer frame decreases.Example 21: The device of any of examples 15-20, where an outer surface of the restrictor section is parallel to an outer surface of the outer frame.Example 22: The device of any of examples 15-21, where a wall of the restrictor section remains parallel to the outer surface of the outer frame as the diameter of the outer frame changes.e-filed RVMP-005 / 001WOSeptember 4, 2025 43730-02028Example 23: The device of any of examples 15-22, where an outer surface of the restrictor section is parallel to the central axis.Example 24: The device of any of examples 15-23, where the diameter of the restrictor section is proportional to the diameter of the vessel in which the blood flow regulation device is positioned.Example 25: The device of any of examples 15-24, where the outlet section expands from a first diameter at its proximal end to a second, larger, diameter at its distal end.Example 26: The device of any of examples 15-25, where an outer surface of the outlet section forms an angle 0 with the central axis and where angle 0 decreases as the diameter of the blood flow regulation device decreases.Example 27: The device of any of examples 15-26, where the outlet section is not covered by the membrane.Example 28: The device of any of examples 15-27, where fluids flowing through the blood flow regulation device flow through one or more openings in the inner frame where the inner frame forms the outlet section.Example 29: The device of example 28, where fluids flowing through the blood flow regulation device will flow through the openings in the outlet section and into the outer frame.Example 30: The device of any of examples 15-27, where fluid leaving the restrictor section has a lower pressure than fluid entering the inlet section.Example 31: A method of controlling the flow of blood through a blood vessel using a blood flow regulation device, including channeling the blood through a blood flow regulation device comprising an outer frame and a blood regulation element, the blood regulation element including an inlet section and a restrictor section, decreasing a cross section of the blood flow through the inlet section, and maintaining the cross section of the blood flow through the restrictor section.Example 32: The method of example 31, where the blood flow regulation device further comprises an outlet section, and the method further comprises increasing the cross section of the blood flow through the outlet section.Example 33: The method of examples 31 or 32, where the inlet section is sized and shapede-filed RVMP-005 / 001WOSeptember 4, 2025 43730-02028 to decrease the cross section of the blood flow in a continuous manner.Example 34: The method of any of examples 31-33, where the cross section of the blood flow through the restrictor section is less than the cross section of the blood flow at a proximal end of the inlet section.Example 35: The method of any of examples 31-34, where the cross section of the blood flow through the restrictor section is proportional to the cross section of a proximal end of the blood flow regulation device.Example 36: The method of any of examples 15-35, where a change in the cross section of the proximal end of the blood flow regulation device results in a proportional change in the cross section of the restrictor section.Example 37: The method of any of examples 31-36 where a diameter of the restrictor section is between approximately 70 and 80 percent of the diameter of the proximal end of the blood flow regulation device.Example 38: The method of any of examples 31-37 where the diameter of the restrictor section is 75 percent of the diameter of the proximal end of the blood flow regulation device.Example 39: The method of any of examples 31-38, where a cross-sectional area of the restrictor section is between approximately 70 and 80 percent of the cross-sectional area of the proximal end of the blood flow regulation device.Example 40: The method of any of examples 31-39, where the cross-sectional area of the restrictor section is 75 percent of the cross-sectional area of the proximal end of the blood flow regulation device.Example 41: The method of any of examples 31-40, where the flow of blood through the blood flow regulation device is greater than zero.Example 42: The method of any of examples 31-41, where the flow of blood through the blood flow regulation device is between approximately 5 percent and 10 percent of the flow of blood through the blood vessel in the absence of any restrictions.Example 43: The method of any of examples 31-42 where blood at the proximal end of the blood flow regulation device has a first pressure which is greater than the pressure of blood at the distal end of the blood flow regulation device.Example 44: The method of any of examples 31-43, where the pressure of the blood at thee-filed RVMP-005 / 001WOSeptember 4, 2025 43730-02028 proximal end of the blood flow regulation device is approximately 5mm Hg less than the pressure of the blood at the distal end of the blood flow regulation device.Example 45: The method of any of examples 31-43, where there is an approximately 5mm Hg drop in pressure between the proximal and distal ends of the blood regulation device.Example 46: A method of setting the size of a restriction in a blood vessel where a blood flow regulation device is positioned in the blood vessel, blood flow regulation device comprising an outer frame and a blood regulation element, the blood regulation element including an inlet section and a restrictor section, the method including the steps of: increasing the diameter of the restrictor section proportionately to increases in the diameter of the blood regulation device, and decreasing the diameter of the restrictor section proportionately to decreases in the diameter of the blood regulation device.Example 47: The method of example 46, where an angle 0 between a wall of an outlet section of the blood flow regulation device and a central axis of the blood flow regulation device decreases as diameter of the restrictor section is decreased.Example 48: The method of examples 46 or 47, where an angle 0 between a wall of an outlet section of the blood flow regulation device and a central axis of the blood flow regulation device decreases as diameter of the restrictor section is decreased.Example 49: A kit for regulating blood flow in a blood vessel comprising at least two blood flow regulation devices according to any of examples 1-30, where at least one of the blood flow regulation devices of the kit includes a smaller outer diameter than at least one other blood flow regulation device of the kit.Example 50: A system for regulating the blood flow in a blood vessel comprising a blood flow regulation device according to any of examples 1-30, and a delivery catheter.Example 51: A blood flow regulation device, the blood flow regulation device being expandible from a first size configured to fit within a catheter lumen to a second size larger than the first size where at least a portion of blood flow regulation device has a diameter which fits within the lumen of a blood vessel, the blood flow regulation device includes a frame, where the frame is substantially covered by a membrane, an inlet section, an first flow opening at a distal end of inlet section, a restrictor section, an outlet section, where outlet section includes a plurality of second flow openings which are arranged radially around outlet section, and a second flow opening frame surrounding second flow openings.e-filed RVMP-005 / 001WOSeptember 4, 2025 43730-02028Example 52: A blood flow regulation device according to example 51, where the second flow openings are elongated proximally to distally, oval in shape with walls which are parallel, and the second flow openings having a continuous diameter along their length when blood flow regulation device is fully deployed.Example 53: A blood flow regulation device according to example 51, where the proximal end of blood flow regulation device is open and positioned within catheter lumen.Example 54: A blood flow regulation device according to example 51 where cylindrical restrictor section 16 tapers from a first diameter equal to the diameter of a proximal end of conical section 32 to a second diameter equal to the diameter of a distal end of cylindrical section 34, the first diameter being larger than the second diameter.Example 55: A method of controlling the flow of blood using a blood flow regulation system comprising a catheter and a blood flow regulation device, where the catheter includes a catheter lumen, and a distal end, and where blood flow regulation device includes an inlet section, an first flow opening at a distal end of inlet section, a restrictor section, and an outlet section comprising at least one second flow opening, where the method includes the steps of inserting a distal end of blood flow regulation system into patient vein, extending blood flow regulation device from the distal end of blood flow regulation system, expanding inlet section to contact an inner wall of the patient vein, opening first flow opening, where blood flowing in the patient vein flows into first flow opening, into outlet section and out of blood flow regulation device through one or more second flow openings, adjusting the flow of blood through second flow openings by moving outlet section into and out of catheter lumen, where the distal end of catheter is used to obstruct the flow of blood through opening.Example 56: A blood flow regulation system includes a catheter including a proximal catheter section, and a distal catheter section, where the proximal catheter section is separable from the distal catheter section 56, a blood flow regulation device collapsible to fit within a catheter lumen of the catheter when the proximal catheter section and the distal catheter section are joined, and a guidewire, where the guidewire extends through the catheter lumen and the blood flow regulation device from the proximal catheter section to the distal catheter section.Example 57: The blood flow regulation system of example 56, where blood flow regulation device includes an expandable outer frame, a first flow opening, a second flowe-filed RVMP-005 / 001WOSeptember 4, 2025 43730-02028 opening 38, foldable protrusions having, the proximal end of foldable protrusions form a second flow opening, a membrane covering the expandable outer frame between the foldable protrusions and the first flow opening and at least a portion of the foldable protrusions, and control wires extending from the foldable protrusions into the proximal catheter section.Example 58: A method of deploying a blood flow regulation device according to Examples 56 or 57, the method comprising the steps of inserting catheter 21 into a body lumen, separating proximal catheter section 54 from distal catheter section 56 to allow blood flow regulation device 10 to expand onto the body lumen until outer frame 13 contacts an inner surface of the body lumen.Example 59: A blood flow regulation system including a catheter, a blood flow regulation device including an outer frame, a guidewire lumen, a membrane, a first flow opening, a second flow opening, where the second flow opening includes a circular opening in membrane, and a blood flow regulator distal to flow opening, where the blood flow regulator is connected to a guide wire extending from guidewire lumen through flow opening and into blood flow regulation device, where the guide wire being movable to position blood flow regulator to obstruct the flow through second flow opening.Example 60: A blood flow regulation system of example 59, where blood flow regulator is positioned within blood flow regulation device when positioned to restrict the flow of blood through second flow opening.Example 61: A blood flow regulation system according to example 60, where blood flow regulator is positioned within a portion of blood flow regulation device when positioned to restrict the flow of blood through second flow opening.Example 62: A blood flow regulation system according to any of examples 59-61 where blood flow regulator comprises a balloon.Example 63: A blood flow regulation system according to example 62 where balloon is inflatable.Example 64: A blood flow regulation system according to example 63, where inflation of balloon changes the degree of restriction of second flow opening.Example 65: A blood flow regulation system according to any of example 59-61, where blood flow regulator comprises a bi-conal element.e-filed RVMP-005 / 001WOSeptember 4, 2025 43730-02028Example 66: A blood flow regulation system according to example 65, where bi-conal element comprises catheter tip and flow regulation element.Example 67: A blood flow regulation system according to example 66, where flow regulation element comprises a cone shape.Example 68: A method of obstructing the flow of blood through a blood flow regulation device according to any of examples 60-67, where guide wire is used to pull blood flow regulator through blood flow regulation device and into second flow opening to obstruct the flow of blood through second flow opening.Example 69: A method according to example 68, where blood flows into first flow opening 36, through blood flow regulation device, around blood flow regulator and out of blood flow regulation device through second flow opening.Example 70: A method according to example 69, where balloon is inflated to obstruct first flow opening 38.Example 71: A method according to example 69, where second flow opening is partially obstructed.Example 72: A method according to example 71, where second flow opening is fully obstructed.Example 73: A blood flow regulation system according to example 59, where blood flow regulator is positioned outside of blood flow regulation device when positioned to restrict the flow of blood through second flow opening.Example 74: A blood flow regulation system according to example 73, where blood flow regulator is positioned distal to the blood flow regulation device when positioned to restrict the flow of blood through second flow opening.Example 75: A blood flow regulation system according to example 74, where blood flow regulator comprises a balloon.Example 76: A blood flow regulation system according to example 75, where the balloon is inflatable.Example 77: A blood flow regulation system according to example 76, where inflation of the balloon changes the degree of restriction of second flow opening.e-filed RVMP-005 / 001WOSeptember 4, 2025 43730-02028Example 78: A blood flow regulation system according to example 74, where blood flow regulator comprises a bi-conal element.Example 79: A blood flow regulation system according to example 78, where bi-conal element comprises catheter tip and flow regulation element.Example 80: A blood flow regulation system according to example 74, where flow regulation element comprises a cone shape.Example 81: A method of obstructing the flow of blood through a blood flow regulation device according to examples 73-80, where guide wire is used to pull blood flow regulator toward blood flow regulation device and into second flow opening to obstruct the flow of blood through second flow opening.Example 82: A method according to example 81, where blood flows around blood flow regulator, into second flow opening, through blood flow regulation device, and out of the blood flow regulation device through first flow opening.Example 83: A method according to example 82, where balloon is inflated to obstruct first flow opening.Example 84: A method according to example 82, where second flow opening is partially obstructed.Example 85: A method according to example 82, where second flow opening is fully obstructed.Example 86: A blood flow regulation system comprising a catheter comprising a catheter lumen and a distal end, a blood flow regulation device including a frame where the frame forms a cylindrical section and a conical section, a first opening at a distal enc of cylindrical section 34, a plurality of elongated openings at a proximal end of conical section, where distal end of catheter forms a proximal end of elongated openings, a guidewire extending from catheter lumen, through blood flow regulation device and past first opening, and a guidewire tip attached to a distal end of guidewire.Example 87: A blood flow regulation system according to example 86, where a first pressure sensor is attached to blood flow regulation system distal to blood flow regulation device.Example 88: A blood flow regulation system according to example 87, where a firste-filed RVMP-005 / 001WOSeptember 4, 2025 43730-02028 pressure sensor is attached to a distal end of guidewire.Example 89: A blood flow regulation system according to example 88, where the first pressure sensor is attached to guidewire tip.Example 90: A blood flow regulation system according to example 86, where a second pressure sensor is attached to blood flow regulation system proximal to blood flow regulation device.Example 91: A blood flow regulation system according to example 90, where second pressure sensor is attached to a distal end of catheter.Example 92: A method of adjusting the flow of blood through a blood flow regulation system according to examples 86-91, where the method comprises the steps of extending blood flow regulation device from catheter lumen, expanding blood flow regulation device into a blood vessel until an outer surface of blood flow regulation device contacts an inner surface of the blood vessel, pulling blood flow regulation device back in to catheter lumen, reducing the size of flow openings.Example 93: A method of adjusting the flow of blood through a blood flow regulation system according to example where the step of reducing the size of flow openings further comprises collapsing a proximal end of conical section into catheter lumen.Example 94: A method of adjusting the flow of blood through a blood flow regulation system according to example 92, where the step of reducing the size of flow openings further comprises moving distal end of catheter along an outer surface of conical section towards cylindrical section.General Considerations

[0109] While various inventive embodiments have been described and illustrated herein, those of ordinary skill in the art will readily envision a variety of other means and / or structures for performing the function and / or obtaining the results and / or one or more of the advantages described herein, and each of such variations and / or modifications is deemed to be within the scope of the inventive embodiments described herein. More generally, those skilled in the art will readily appreciate that all structure, parameters, dimensions, materials, functionality, and configurations described herein are meant to be an example and that thee-filed RVMP-005 / 001WOSeptember 4, 2025 43730-02028 actual structure, parameters, dimensions, materials, functionality, and configurations will depend upon the specific application or applications for which the inventive teachings is / are used. Those skilled in the art will recognize or be able to ascertain using no more than routine experimentation, many equivalents to the specific inventive embodiments described herein. It is, therefore, to be understood that the foregoing embodiments are presented by way of example only and that, within the scope of the claims supported by the present disclosure, and equivalents thereto, inventive embodiments may be practiced otherwise than as specifically described and claimed. Inventive embodiments of the present disclosure are also directed to each individual feature, system, article, structure, material, kit, functionality, step, and method described herein. In addition, any combination of two or more such features, systems, articles, structure, materials, kits, functionalities, steps, and methods, if such are not mutually inconsistent, is included within the inventive scope of the present disclosure. Some embodiments may be distinguishable from the prior art for specifically lacking one or more features / elements / functionality (i.e., claims directed to such embodiments may include negative limitations).

[0110] Also, as noted, various inventive concepts are embodied as one or more methods, of which an example has been provided. The acts performed as part of the method may be ordered in any suitable way. Accordingly, embodiments may be constructed in which acts are performed in an order different than illustrated, which may include performing some acts simultaneously, even though shown as sequential acts in illustrative embodiments.

[0111] Any and all references to publications or other documents, including but not limited to, patents, patent applications, articles, webpages, books, etc., presented anywhere in the present application, are herein incorporated by reference in their entirety. Moreover, all definitions, as defined and used herein, should be understood to control over dictionary definitions, definitions in documents incorporated by reference, and / or ordinary meanings of the defined terms.

[0112] The indefinite articles “a” and “an,” as used herein in the specification and in the claims, unless clearly indicated to the contrary, should be understood to mean “at least one.” The terms “can” and “may” are used interchangeably in the present disclosure, and indicate that the referred to element, component, structure, function, functionality, objective, advantage, operation, step, process, apparatus, system, device, result, or clarification, has the ability to be used, included, or produced, or otherwise stand for the proposition indicatede-filed RVMP-005 / 001WOSeptember 4, 2025 43730-02028 in the statement for which the term is used (or referred to) for a particular embodiment(s).

[0113] The phrase “and / or,” as used herein in the specification and in the claims, should be understood to mean “either or both” of the elements so conjoined, i.e., elements that are conjunctively present in some cases and disjunctively present in other cases. Multiple elements listed with “and / or” should be construed in the same fashion, i.e., “one or more” of the elements so conjoined.

[0114] Other elements may optionally be present other than the elements specifically identified by the “and / or” clause, whether related or unrelated to those elements specifically identified. Thus, as a non-limiting example, a reference to “A and / or B”, when used in conjunction with open ended language such as “comprising” can refer, in one embodiment, to A only (optionally including elements other than B); in another embodiment, to B only (optionally including elements other than A); in yet another embodiment, to both A and B (optionally including other elements); etc.

[0115] As used herein in the specification and in the claims, “or” should be understood to have the same meaning as “and / or” as defined above. For example, when separating items in a list, “or” or “and / or” shall be interpreted as being inclusive, i.e., the inclusion of at least one, but also including more than one, of a number or list of elements, and, optionally, additional unlisted items. Only terms clearly indicated to the contrary, such as “only one of’ or “exactly one of,” or, when used in the claims, “consisting of,” will refer to the inclusion of exactly one element of a number or list of elements. In general, the term “or” as used herein shall only be interpreted as indicating exclusive alternatives (i.e., “one or the other but not both”) when preceded by terms of exclusivity, such as “either,” “one of,” “only one of,” or “exactly one of.”

[0116] “Consisting essentially of,” when used in the claims, shall have its ordinary meaning as used in the field of patent law.

[0117] As used herein in the specification and in the claims, the phrase “at least one,” in reference to a list of one or more elements, should be understood to mean at least one element selected from any one or more of the elements in the list of elements, but not necessarily including at least one of each and every element specifically listed within the list of elements and not excluding any combinations of elements in the list of elements. This definition also allows that elements may optionally be present other than the elements specificallye-filed RVMP-005 / 001WOSeptember 4, 2025 43730-02028 identified within the list of elements to which the phrase “at least one” refers, whether related or unrelated to those elements specifically identified. Thus, as a non-limiting example, “at least one of A and B” (or, equivalently, “at least one of A or B,” or, equivalently “at least one of A and / or B”) can refer, in one embodiment, to at least one, optionally including more than one, A, with no B present (and optionally including elements other than B); in another embodiment, to at least one, optionally including more than one, B, with no A present (and optionally including elements other than A); in yet another embodiment, to at least one, optionally including more than one, A, and at least one, optionally including more than one, B (and optionally including other elements); etc.

[0118] In the claims, as well as in the specification above, all transitional phrases such as “comprising,” “including,” “carrying,” “having,” “containing,” “involving,” “holding,” “composed of,” and the like are to be understood to be open-ended, i.e., to mean including but not limited to. Only the transitional phrases “consisting of’ and “consisting essentially of’ shall be closed or semi-closed transitional phrases, respectively, as set forth in the United States Patent Office Manual of Patent Examining Procedures, Section 2111.03.

Claims

e-filed RVMP-005 / 001WOSeptember 4, 2025 43730-02028What is currently claimed:

1. A blood flow regulation device comprising: an outer frame surrounding a central axis; a blood regulation element positioned in the outer frame, the blood regulation element comprising: an inner frame positioned within the outer frame and only connected to the outer frame at proximal and distal ends of the outer frame, such that: a proximal end of the inner frame is connected to a proximal end of the outer frame; and a distal end of the inner frame is connected to a distal end of the outer frame, and a membrane arranged to cover at least a portion of the inner frame; and a central axis running through a center of at least one of the outer frame and the blood regulation element.

2. The device of claim 1, wherein the outer frame is tubular and includes a diameter which is substantially continuous from the proximal end to the distal end.

3. The device of claims 1, wherein no portion of the outer frame is covered by a membrane.

4. The device of claim 1, wherein the blood flow regulation device is radially expandable.

5. The device of claim 1, wherein the blood blow regulation device radially expands to conform to a diameter of a vessel in which it is placed.e-filed RVMP-005 / 001WOSeptember 4, 2025 43730-020286. The device of claim 1, wherein the outer frame comprises a wire mesh.

7. The device of claim 6, wherein the wire mesh comprises Nitinol struts.

8. The device of claim 1, wherein the membrane creates a fluid channel through the blood regulation element.

9. The device of claim 1, wherein fluid exiting the blood flow regulation device flows into the space between the inner and outer frames.

10. The device of claim 1, wherein the inner frame floats with respect to the outer frame between the proximal and distal ends of the outer frame.

11. The device of any of claims 1-10, wherein the length of the blood flow regulation device decreases as the diameter of the outer frame increases.

12. The device of any of claims 1-11, wherein the inner frame is more rigid than the outer frame.

13. The device of any of claims 1-12, wherein the inner frame and the outer frame comprise Nitinol struts, the struts of the inner frame being more rigid than the struts of the outer frame.

14. The device of claim 13, wherein the struts of the inner frame are thicker than the struts of the outer frame.

15. The device of any of claims 1-14, wherein the blood regulation element comprises:e-filed RVMP-005 / 001WOSeptember 4, 2025 43730-02028 an inlet section including a proximal end attached to the proximal end of the outer frame; a restrictor section including a proximal end attached to a distal end of the inlet section; and an outlet section including a proximal end attached to a distal end of the restrictor section and including a distal end attached to the distal end of the outer frame; and the membrane covers at least one of and preferably both of the inlet section and the restrictor section.

16. The device of any of claims 1-15, where in the blood regulation element includes a substantially hourglass shape.

17. The device of any of claims 1-16, wherein the inlet section tapers from a first diameter at its proximal end to a second, smaller, diameter at its distal end.

18. The device of any of claims 15-17, wherein an outer surface of the inlet section forms an angle a with the central axis wherein angle a decreases as the diameter of the blood flow regulation device decreases.

19. The device of any of claims 15-18, wherein the restrictor section has a continuous diameter from its proximal to its distal end.

20. The device of any of claims 15-19, wherein: the diameter of the restrictor section is proportional to the diameter of the outer frame; the diameter of the outer frame decreases as the diameter of the outer frame decreases.

21. The device of any of claims 15-20, wherein an outer surface of the restrictor section is parallel to an outer surface of the outer frame.e-filed RVMP-005 / 001WOSeptember 4, 2025 43730-0202822. The device of any of claims 15-21, wherein a wall of the restrictor section remains parallel to the outer surface of the outer frame as the diameter of the outer frame changes.

23. The device of any of claims 15-22, wherein an outer surface of the restrictor section is parallel to the central axis.

24. The device of any of claims 15-23, wherein the diameter of the restrictor section is proportional to the diameter of the vessel in which the blood flow regulation device is positioned.

25. The device of any of claims 15-24, wherein the outlet section expands from a first diameter at its proximal end to a second, larger, diameter at its distal end.

26. The device of any of claims 15-25, wherein an outer surface of the outlet section forms an angle 0 with the central axis and wherein angle 0 decreases as the diameter of the blood flow regulation device decreases.

27. The device of any of claims 15-26, wherein the outlet section is not covered by the membrane.

28. The device of any of claims 15-25, wherein fluids flowing through the blood flow regulation device flow through one or more openings in the inner frame where the inner frame forms the outlet section.

29. The device of claim 28, wherein fluids flowing through the blood flow regulation device will flow through the openings in the outlet section and into the outer frame.e-filed RVMP-005 / 001WOSeptember 4, 2025 43730-0202830. The device of any of claims 15-25, wherein fluid leaving the restrictor section has a lower pressure than fluid entering the inlet section.

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