An in vitro testing system and method for interventional left ventricular assist devices

Abstract

This invention discloses an in vitro testing system and method for interventional left ventricular assist devices. The system includes a circulatory loop system, a control system, and a data acquisition system. The circulatory loop system includes a left ventricular module, a mitral valve simulator, an aortic valve simulator, an arterial vessel module, a venous module, a right atrium module, a right ventricular module, a tricuspid valve simulator, a pulmonary valve simulator, a pulmonary vessel module, a left atrium module, and an electrically operated throttle valve. The control system includes a host computer and a controller, which simulates the hemodynamic characteristics of the circulatory system under different heart failure states by adjusting control parameters. The data acquisition system includes pressure sensors and flow sensors for measuring pressure and flow signals at different preset points in the circulatory loop system. The data acquisition system communicates with the host computer in real time. This invention's testing system can simulate hemodynamics under different heart failure states and can be used for in vitro testing of various interventional left ventricular assist devices.

Description

Technical Field

[0001] This invention relates to an in vitro testing system and method for an interventional left ventricular assist device, belonging to the technical field of medical device ventricular assist devices. Background Technology

[0002] Ventricular assist devices (VADs) maintain hemodynamics by increasing cardiac output in patients with heart failure by assisting the ventricles in pumping blood. Different types of VADs operate on different technical principles. For example, implantable ventricular assist pumps (LVADs) and intra-aortic blood pumps (Impella) are transvalvular VADs that pump blood directly from the left ventricle to the ascending aorta, increasing cardiac output while reducing cardiac preload. In contrast, intra-aortic balloon pumps (IABPs) and intra-aortic axial flow pumps (Aortix and ModulHeart) are intra-aortic VADs that increase cardiac output by reducing cardiac afterload.

[0003] Ventricular assist devices (VAPs) are coupled with the native heart, exhibiting different hemodynamic characteristics under varying heart failure states, thus requiring different assist flow rates. Preclinical development of VAPs requires animal testing to assess their hemodynamic and other performance characteristics. Animal experiments are often time- and economically costly. In vitro simulated blood circulation systems can, to some extent, replace animal experiments, thereby shortening the development time and expense of cardiovascular devices.

[0004] Current testing systems involve installing a ventricular assist device (VAD) into the circulatory system and then adjusting heart rate, preload, and afterload parameters to simulate the hemodynamic characteristics of specific heart failure states. This testing system differs significantly from the real human circulatory system and cannot reflect the compensatory capacity of the human heart (Frank-Starling mechanism). Traditional testing systems struggle to measure the impact of transaortic valve interventional pumps (Impella) on the native heart's cardiac output. For VAD devices such as intraaortic balloon pumps (IABP) and intraaortic axial flow pumps (Aortix and ModulHeart), their assistive effect depends on the residual contractile capacity of the native heart, and the effect on cardiac output improvement varies under different operating conditions; existing in vitro testing systems cannot adequately measure this aspect. Furthermore, these devices can affect cerebral blood flow, and traditional in vitro testing systems lack assessment of the impact on carotid and descending aortic perfusion flow, failing to accurately reflect the hemodynamic characteristics of the coupling between the VAD and the ventricle within the aorta.

[0005] Therefore, there is a need to provide a new in vitro testing system and method for ventricular assist devices to solve the above problems. Summary of the Invention

[0006] The purpose of this invention is to solve the above-mentioned problems and provide an in vitro testing system and method for interventional left ventricular assist devices. This system can reflect the compensatory capacity of the native heart, evaluate the impact of the transaortic ventricular assist device on the cardiac output of the native heart during operation, and test the impact of the ventricular assist device placed in the aorta on the carotid and renal artery flow, thus guiding the structural optimization design.

[0007] To achieve the above objectives, the present invention adopts the following technical solution: This invention provides an in vitro testing system for an interventional left ventricular assist device. The in vitro testing system includes a circulatory loop system, a control system, and a data acquisition system. The circulatory loop system comprises a left ventricular module, a mitral valve simulator, an aortic valve simulator, an arterial vessel module, a venous module, a right atrium module, a tricuspid valve simulator, a pulmonary valve simulator, a pulmonary vessel module, a left atrium module, and an electrically operated throttle valve. These modules are connected via silicone tubing to simulate the directional flow of blood driven by the heart in the human circulatory system. The control system includes a host computer and a controller. The controller includes a ventricular drive control module, a gas supply control module, and an electrically operated throttle valve control module, which simulates the hemodynamic characteristics of the circulatory system under different heart failure states by adjusting control parameters. The data acquisition system includes pressure sensors and flow sensors to measure pressure and flow signals at different preset points in the circulatory loop system. The data acquisition system communicates with the host computer to evaluate the hemodynamic state of the circulatory system in real time.

[0008] Furthermore, the left ventricular module includes a first pulsatile pump, a first chamber, and a left ventricular model to simulate the pumping of blood by the left ventricle; the arterial module includes an aortic model, a manual throttle valve, and a collecting chamber, with the aortic inlet connected to the outlet of the left ventricular module, flowing to different branch arteries, and converging through multiple collecting chambers before connecting to the venous module; the venous module includes a second chamber and a pressure controller, which adjusts the pressure and compliance of the main vein by changing the gas pressure above the liquid surface in the second chamber; the right atrial module includes a third chamber and a first bellows assembly, with the inlet of the third chamber connected to the venous module and the outlet connected to the right ventricular model, simulating the right atrium through changes in the volume of the bellows. The filling of the atrium; the right ventricular module includes a second pulsatile pump, a fourth chamber, and a right ventricular model. The fourth chamber is connected to the right atrium via a tricuspid valve simulator and to the pulmonary vascular module via a pulmonary valve simulator, used to simulate the directional pumping function of the right ventricle, pumping blood from the right atrium to the pulmonary vascular module; the pulmonary vascular module includes a fifth chamber and a second corrugated tube assembly. The inlet of the fifth chamber is connected to the right ventricular module, and the outlet is connected to the left atrial module. The second corrugated tube assembly simulates the compliance of the pulmonary vessels; the left atrial module includes a sixth chamber and a third corrugated tube assembly, connected upstream to the pulmonary vascular module and downstream to the left ventricular module. The volume change of the third corrugated tube assembly simulates the filling of the left atrium.

[0009] Furthermore, the right ventricular module has the same structure as the left ventricular module; the first chamber of the left ventricular module is connected to the left atrium via a mitral valve simulator, to the arterial blood vessel module via an aortic valve simulator, and to the first pulsating pump via a pagoda connector; the left ventricular model is placed in the first chamber, and pure water is filled between the left ventricular model and the first chamber; the pulsating flow generated by the pulsating pump changes the volume of pure water in the first chamber, thereby driving the contraction and relaxation of the left ventricular model; a water filling valve and a venting valve are provided at the top of the first chamber for filling with pure water.

[0010] Furthermore, the left ventricular model comprises three layers of flexible material: an inner wall, a middle layer, and an outer wall. The inner wall material is smooth and simulates the endocardium, the middle layer simulates the myocardium, and the outer wall is used to withstand the driving pressure of pure water. The elastic modulus of the inner wall, middle layer, and outer wall materials of the ventricular model decreases sequentially. The middle layer material is relatively thick, and the elastic deformation in the thickness direction of the middle layer is large during left ventricular pulsation, which can reflect the influence of ventricular preload and afterload changes on ventricular volume. The thickness of the inner wall material is 0.5-2 mm, the thickness of the middle layer material is 8-11 mm, and the thickness of the outer wall material is 0.5-1 mm.

[0011] Furthermore, the right ventricular model has the same structure as the left ventricular model; the inner wall material of the right ventricular model has a thickness of 0.5-1 mm, the middle layer material has a thickness of 3-4 mm, and the outer wall material has a thickness of 0.2-0.6 mm.

[0012] Furthermore, the aortic valve is a bioprosthetic valve or a polymer valve with the same shape as the human aortic valve. The mitral valve simulator, tricuspid valve simulator, and pulmonary valve simulator can be ordinary tubular check valves, or mechanical valves, bioprosthetic valves, or polymer valves.

[0013] Furthermore, the aortic vessel model includes the common carotid artery, vertebral artery, axillary artery, celiac trunk artery, superior mesenteric artery, renal artery, inferior mesenteric artery, internal iliac artery, and femoral artery, and is made of biomimetic silicone material, possessing compliance similar to native arterial vessels; the femoral artery is equipped with a vascular interventional pathway for the delivery of interventional ventricular assist devices.

[0014] Furthermore, the fluid collection cavity includes a brain fluid collection cavity, an upper limb fluid collection cavity, an abdominal fluid collection cavity, and a lower limb fluid collection cavity; the brain fluid collection cavity is connected to the common carotid artery and the vertebral artery; the upper limb fluid collection cavity is connected to the axillary artery; the abdominal fluid collection cavity is connected to the celiac trunk artery, the superior mesenteric artery, and the renal artery; the lower limb fluid collection cavity is connected to the inferior mesenteric artery, the internal iliac artery, and the femoral artery; the fluid collection cavity gathers arterial branches and then connects to the venous module.

[0015] Furthermore, the electric throttle valve is installed between the fluid collection chamber and the venous module to adjust systemic circulation resistance; the pipelines of the pulmonary vascular module and the left atrial module are also equipped with electric throttle valves to simulate pulmonary circulation resistance; the manual throttle valve is installed in each branch of the arterial blood vessel to regulate the flow distribution of different blood vessel branches.

[0016] Furthermore, the top of the vein module is equipped with a filling valve and a pneumatic interface. The filling valve is used to inject test liquid into the entire circulation system, and the pneumatic interface is connected to a pressure controller to control the pressure in the vein cavity. The test liquid is animal blood or a water-glycerol mixture.

[0017] Furthermore, the ventricular drive control module can drive the first and second pulse pumps to generate biomimetic pulsating blood flow according to different frequencies, stroke volume, and systolic-diastolic ratios, periodically changing the volume of pure water in the cavity to drive ventricular contraction and relaxation; the gas supply control module adjusts the pressure and compliance of the second sealed cavity of the venous module through a pressure controller; and the electric throttle valve control module changes the preload and afterload of the circulatory system by adjusting the opening of the throttle valve.

[0018] The present invention also provides a method for conducting in vitro testing of interventional left ventricular assist devices using the aforementioned in vitro testing system, the method comprising the following steps: (1) Adjust the control parameters so that the heart rate, cardiac output, aortic blood pressure and arterial branch flow signals of the test system are consistent with the hemodynamic parameters under a specific heart failure state, and record them as baseline data; (2) The interventional left ventricular assist device is delivered via a sheath to the descending aorta or the location across the aortic valve through a vascular interventional pathway at the femoral artery location; (3) Activate the left ventricular assist device, measure the cardiac output, pressure and flow signals of the aorta and branch arteries under the preset working conditions, and record them as experimental data; (4) Compare experimental data with baseline data to evaluate the effects of the ventricular assist device on cardiac output, brain and kidney perfusion pressure and flow rate under preset operating conditions; (5) Change the baseline data and the operating conditions of the ventricular assist device to evaluate the hemodynamic performance of the ventricular assist device under different heart failure states and different operating conditions.

[0019] The beneficial effects of this invention are: In the in vitro testing system and method for the interventional left ventricular assist device provided by this invention, a ventricular model made of three layers of flexible material is used. The elastic deformation of the ventricular wall during systole and diastole simulates the isovolumetric relaxation and isovolumetric contraction phases, thereby simulating the impact of preload and afterload changes on cardiac output during ventricular assist device operation. Simultaneously, this invention includes a biomimetic aortic vascular model, which can assess the impact of ventricular assist device operation on brain and kidney perfusion flow. Attached Figure Description

[0020] To more clearly illustrate the specific embodiments of the present invention, the accompanying drawings used in the specific embodiments will be briefly introduced below. Obviously, the drawings described below are only used to illustrate some embodiments of the present invention. For those skilled in the art, other drawings can be obtained from these drawings without creative effort.

[0021] Figure 1 This is an isometric view of the in vitro testing system of the interventional left ventricular assist device according to an embodiment of the present invention.

[0022] Figure 2 This is a schematic diagram of a loop system according to an embodiment of the present invention.

[0023] Figure 3A This is a schematic diagram of the left ventricular module structure according to an embodiment of the present invention.

[0024] Figure 3B This is a partial cross-sectional view of the left ventricular module according to an embodiment of the present invention.

[0025] Figure 3C This is a cross-sectional view of the left ventricle model according to an embodiment of the present invention.

[0026] Figure 4A This is an exploded view of the aortic valve simulator according to an embodiment of the present invention.

[0027] Figure 4B This is a schematic diagram of a polymeric aortic valve according to an embodiment of the present invention.

[0028] Figure 5 This is a schematic diagram of the arterial blood vessel module according to an embodiment of the present invention.

[0029] Figure 6 This is a schematic diagram of the upper limb fluid collection cavity according to an embodiment of the present invention.

[0030] Figure 7A This is a schematic diagram of the vein module according to an embodiment of the present invention.

[0031] Figure 7B This is a schematic diagram of the vein module from another perspective according to an embodiment of the present invention.

[0032] Figure 8 This is a schematic diagram of the right atrial module according to an embodiment of the present invention.

[0033] Figure 9 This is a schematic diagram of the right ventricular module according to an embodiment of the present invention.

[0034] Figure 10A This is a schematic diagram of the shape changes of the left ventricular model during normal pulsation according to an embodiment of the present invention.

[0035] Figure 10B This is a schematic diagram of the shape change of the left ventricular model when the afterload decreases according to an embodiment of the present invention.

[0036] Figure 10C This is a schematic diagram of the shape change of the left ventricular model when the preload decreases according to an embodiment of the present invention.

[0037] Figure 11 This is a schematic diagram of an embodiment of the present invention used for in vitro testing of a transaortic valve axial flow pump.

[0038] Figure 12 This is a schematic diagram of an embodiment of the present invention used for in vitro testing of a modular intra-aortic axial flow pump.

[0039] Figure 13 This is a schematic diagram of an embodiment of the present invention used for in vitro testing of intra-aortic balloon counterpulsation. Detailed Implementation

[0040] The present invention will be further illustrated below with reference to specific embodiments. It should be understood that these embodiments are for illustrative purposes only and are not intended to limit the scope of the invention. Furthermore, it should be understood that after reading this invention, those skilled in the art can make various alterations or modifications to the invention, and these equivalent forms also fall within the scope defined by the appended claims.

[0041] Figure 1 This is an isometric view of an in vitro testing system for an interventional left ventricular assist device provided in an embodiment of the present invention. The in vitro testing system includes a circulatory loop system 1, a control system 2, and a data acquisition system 3. The circulatory loop system 1 is connected to the control system 2 and the data acquisition system 3. The circulatory loop system 1 is used to simulate the directional flow of blood driven by the heart in the human circulatory system; the control system 2 simulates the hemodynamic characteristics of the circulatory system under different heart failure states by adjusting control parameters; the data acquisition system 3 is used for data acquisition and real-time evaluation of the hemodynamic state of the circulatory system.

[0042] See Figure 2 The circulatory loop system 1 of this embodiment includes a left ventricular module 11, a mitral valve simulator 12, an aortic valve simulator 13, an arterial vessel module 14, a venous module 15, a right atrium module 16, a right ventricular module 17, a tricuspid valve simulator 18, a pulmonary valve simulator 19, a pulmonary vessel module 1110, a left atrium module 1111, and an electrically operated throttle valve 1112. The modules are connected by silicone tubing. See also... Figure 3A , Figure 3B The left ventricular module 11 of this embodiment includes a first pulsatile pump 111, a first chamber 112, and a left ventricular model 113. The first chamber 112 is connected to the left atrial module 1111 via a mitral valve simulator 12, and to the arterial module 14 via an aortic valve simulator 13. It is also connected to the first pulsatile pump 111 via a pagoda connector 1121. The left ventricular model 113 of this embodiment has an inlet 1131 and an outlet 1132, which are respectively connected to the mitral valve simulator 12 and the aortic valve simulator 13. Through the contraction and relaxation process of the left ventricular model 113, the fluid of the left atrial module 1111 can be pumped directionally into the arterial module 14. The space between the left ventricular model 113 and the first chamber 112 is filled with pure water. A water filling valve 1122 is provided on the top of the first chamber 112 for injecting pure water between the first chamber 112 and the left ventricular model 113. A venting valve 1123 is also provided on the top of the first chamber 112 for venting during the pure water injection process.

[0043] The first pulsating pump 111 in this embodiment of the invention can generate biomimetic pulsating blood flow according to different frequencies, stroke volumes, and systolic-diastolic time ratios. This pulsating flow is delivered to the first chamber 112 via a pagoda connector 1121. The reciprocating motion of the internal piston periodically changes the volume of pure water within the chamber, utilizing the incompressibility of pure water to drive the left ventricular model's contraction and relaxation, thus simulating the hemodynamic states of different heart failure patients. The first pulsating pump in this embodiment can be a Vitro Super Pump, a widely used pulsating pump in the art. The Vitro Super Pump is a digitally controlled piston pump that can generate physiological cardiac blood flow and has high scalability. This embodiment of the invention connects the Vitro Super Pump to the first chamber, enabling the left ventricular model to generate biomimetic pulsating flow.

[0044] See Figure 3C The left ventricular model 113 of this invention comprises three layers of flexible material: an inner wall 1133, a middle layer 1134, and an outer wall 1135. The inner wall material simulates the endocardium, the middle layer simulates the myocardium, and the outer wall withstands the driving pressure of pure water. The elastic modulus of the inner wall, middle layer, and outer wall materials of the left ventricular model 113 decreases sequentially. The outer wall material is thin, tough, and has low elasticity, mainly serving to isolate and transmit pressure; its elasticity change should be as small as possible. The thickness of the inner wall material is 0.5-2 mm, the thickness of the middle layer material is 8-11 mm, and the thickness of the outer wall material is 0.5-1 mm. During the left ventricular contraction and relaxation, the middle layer 1134 exhibits significant elastic deformation in the thickness direction. The change in thickness reflects the influence of left ventricular preload and afterload changes on ventricular volume. This characteristic can simulate the compensatory capacity (Frank-Starling mechanism) of the human native heart, improving the simulation accuracy of the test bench. The inner and outer wall materials can be silicone membranes or polyurethane membranes, and the middle layer material can be foam silicone or other customized composite materials, without limitation.

[0045] See Figure 4A , Figure 4BThe aortic valve simulator 13 of this embodiment includes a first interface 131, a second interface 132, a polymer aortic valve 133, a sealing ring 134, and a pressure measuring line 135. The first interface 131 is connected to the first chamber 112 of the left ventricle model, and the second interface 132 is connected to the first interface 131. The polymer aortic valve 133 is disposed between the two interfaces as a one-way valve, including a polymer valve 1331 and a valve frame 1332, with the valve frame 1332 bonded and fixed to the second interface 132. The pressure measuring line 135 is connected to the first interface 131 and is used to detect the pressure signal within the left ventricle model 113 in real time. The structure of the polymer aortic valve 133 used in this embodiment is similar to that of the native aortic valve, ensuring that the flow parameters of the fluid pumped by the left ventricle model to the arterial vessels are similar to those in real human conditions, resulting in high simulation accuracy.

[0046] See Figure 5 The arterial vascular module 14 of this embodiment includes an aortic vascular model 141, a manual throttle valve 142, and a collection chamber 143. The arterial vascular branches include the common carotid artery 1411, vertebral artery 1412, axillary artery 1413, celiac trunk artery 1414, superior mesenteric artery 1415, renal artery 1416, inferior mesenteric artery 1417, internal iliac artery 1418, and femoral artery 1419. The arterial vascular module is manufactured based on CT data of the human heart using injection molding or 3D printing technology. The material is biomimetic silicone, which has compliance similar to that of native arterial vessels. In this embodiment of the invention, the fluid collection chamber 143 includes a brain fluid collection chamber 1431, an upper limb fluid collection chamber 1432, an abdominal fluid collection chamber 1433, and a lower limb fluid collection chamber 1434. The common carotid artery 1411 and vertebral artery 1412 are connected to the brain fluid collection chamber 1431; the axillary artery 1413 is connected to the upper limb fluid collection chamber 1432; the celiac trunk artery 1414, superior mesenteric artery 1415, and renal artery 1416 are connected to the abdominal fluid collection chamber 1433; and the inferior mesenteric artery 1417, internal iliac artery 1418, and femoral artery 1419 are connected to the lower limb fluid collection chamber 1434. The four fluid collection chambers are connected to the venous module 15 via an electric throttle valve 1112 and silicone tubing. The electric throttle valve 1112 is used to adjust systemic circulation resistance. Each aortic branch is equipped with a manual throttle valve 142 for fine-tuning the arterial resistance, thereby adjusting the flow distribution of the arterial branches to be similar to the flow of the human aortic branches. See also... Figure 6This is a schematic diagram of the upper limb fluid collection chamber 1432 in an embodiment of the present invention. It is connected to the axillary artery 1413 via a vascular interface 14321, to the brain fluid collection chamber via an interface 14322, and to a venous cavity via a silicone tube via an interface 14323. An air vent valve 14324 is provided at the top of the upper limb fluid collection chamber 1432 for venting during pre-filling with test fluid, and a drain valve 14325 is provided at the bottom for draining after testing. Other fluid collection chambers are structurally similar to the upper limb fluid collection chamber 1432. In this embodiment of the present invention, a vascular interventional pathway 1420 is provided at the femoral artery 1419 for delivering an interventional left ventricular assist device to the descending aorta. In the arterial vascular model of this embodiment of the present invention, pressure measuring tubes are provided at the ascending aorta, descending aorta, and renal artery locations, see [reference]. Figure 5 Flow sensors are located at P1, P2, P3, and P4; and at the locations of the brachiocephalic trunk, left carotid artery, subclavian artery, descending aorta, and renal artery. (See also...) Figure 5 F1, F2, F3, F4, and F5 can be used to assess the hemodynamics of arterial vessels through blood pressure and flow signals. The sensor in this embodiment of the invention is an ultrasonic flow probe, which can be an ultrasonic flow probe from Transonic.

[0047] See Figure 7A , Figure 7B The venous module 15 of this embodiment includes a second cavity 151 and a pressure controller 152. The top of the second cavity 151 is provided with an filling valve 1511 and a pneumatic interface 1512. The filling valve 1511 is used to inject test liquid into the entire circulatory system; the test liquid is animal blood or a water-glycerol mixture. The pneumatic interface 1512 is used to connect to a first pressure controller 152. When energized, the first pressure controller 152 can adjust the internal pressure of the second cavity 151 in real time, thereby adjusting the pressure of the main vein and the cavity compliance. The pressure controller 152 of this embodiment can be an ALICAT PCD series pressure controller, and is not limited thereto. The bottom of the second cavity 151 is provided with a set of inlet 1513, an outlet 1514, a pressure measuring tube 1515 and a drain valve 1516. The inlet 1513 is used to connect with the arterial blood vessel module, the outlet 1514 is used to connect with the right atrium module, the pressure measuring tube 1515 is used to connect with the pressure sensor, and the drain valve 1516 is used to drain the test liquid after the measurement is completed.

[0048] See Figure 8The right atrial module 16 of this embodiment includes a third chamber 161 and a first bellows assembly 162. The third chamber 161 includes an inlet port 1611, an outlet port 1612, and a pressure measuring line 1613. The inlet port 1611 is connected to the venous module via a silicone tube, and the outlet port 1612 is connected to the right ventricular module 17. The pressure measuring line 1613 is used to connect a pressure sensor to measure the pressure of the right atrium in real time. The first bellows assembly 162 includes a support 1621, a bellows 1622, a spring 1623, and an exhaust pipe 1624. The volume and shape changes of the bellows 1622 and the spring 1623 simulate the filling state of the right atrium and receive venous return blood from the venous module. The exhaust valve 1624 is used to exhaust air when the circulatory system is pre-filled with test fluid.

[0049] See Figure 9 The right ventricular module 17 of this embodiment includes a second pulsating pump 171, a fourth chamber 172, and a right ventricular model 173 (not shown in the figure). The fourth chamber 172 is connected to the right atrial module 16 via a tricuspid valve simulator 18 and to the pulmonary vessel module 1110 via a pulmonary valve simulator 19 to ensure unidirectional pulmonary circulation. It is also connected to the second pulsating pump 171 via a pagoda connector 1721. A water filling valve 1722 is provided at the top of the fourth chamber 172 for injecting pure water into it. An exhaust valve 1723 is also provided at the top of the fourth chamber 172 for venting during the pure water injection process. The right ventricular model has the same structure as the left ventricular model, also comprising three layers of flexible material: an inner wall material thickness of 0.5-1 mm, a middle layer material thickness of 3-4 mm, and an outer wall material thickness of 0.2-0.6 mm. The specific assembly structure of the right ventricular module is the same as that of the left ventricular module and will not be described further here.

[0050] The one-way valves in the mitral valve simulator 12, tricuspid valve simulator 18, and pulmonary valve simulator 19 of this invention can be ordinary check valves, mechanical valves, or polymer valves, and are not limited thereto. Their assembly structure is similar to that of the aortic valve simulator, and will not be described in detail here.

[0051] The pulmonary vascular module 1110 and the left atrial module 1111 of this embodiment have the same structure as the right atrial module 16. The compliance of the pulmonary vessels and the filling state of the left atrium are simulated by the volume and shape changes of the bellows and springs.

[0052] The control system 2 of this invention has ventricular drive control, gas supply control, and electric throttling valve control functions. It can drive the first and second pulse pumps to generate biomimetic pulsating blood flow according to different operating frequencies, stroke volume, and systolic-diastolic time ratios, driving the ventricles to simulate different heart failure states through systolic and diastolic movements. The control system 2 can adjust the pressure and compliance of the second closed cavity of the venous module through a pressure controller, and change the preload and afterload of the circulatory system by controlling the opening of the electric throttling valve.

[0053] In this embodiment of the invention, pressure sensors are installed in the left ventricular module, aortic module, venous module, right atrial module, pulmonary vascular module, and left atrial module of the circulatory loop system to monitor the pressure values ​​at each module location. Simultaneously, ultrasonic flow sensors are installed in the ascending and descending aorta of the aorta. The data acquisition system in this embodiment uses ADInstruments' PowerLab C physiological data acquisition and analysis system. This system acquires blood pressure and flow signals through a bridge amplifier and a tubing flow recorder, respectively, and is equipped with LabChart recording and analysis software. Pressure and flow data are recorded and analyzed via a host computer.

[0054] Figure 10A This is a schematic diagram illustrating the shape changes of a left ventricular model during normal heartbeat, according to an embodiment of the present invention. During the isovolumetric contraction phase, a first pulsatile pump injects liquid into the first chamber. The liquid compresses the left ventricular model, causing the outer wall of the model to contract along its thickness direction while the inner wall shape remains unchanged. During this process, the pressure of the left ventricular model on the internal liquid gradually increases but remains less than the aortic pressure. As the amount of liquid injected by the pulsatile pump increases, the wall thickness of the left ventricular model decreases, and the internal pressure of the left ventricular model further increases. This simulates the process during isovolumetric contraction, where the intraventricular pressure increases while the volume remains constant. When the intraventricular pressure of the left ventricular increases to exceed the aortic pressure, the aortic valve opens, entering the ejection phase. Under the action of the pulsatile pump, pure water continuously compresses the left ventricular model, causing the inner wall of the left ventricular chamber to contract and its volume to decrease, completing the ejection process. Figure 10A The left ventricular model is shown in the diagram at the end of ejection. During the isovolumetric relaxation phase, the pressure within the left ventricular model is greater than the pressure in the left atrium. The pulsatile pump draws fluid out of the first chamber, the outer wall of the left ventricular model begins to relax, the inner wall shape remains unchanged, the left ventricular wall thickness increases, and the internal pressure gradually decreases. This simulates the process of left ventricular pressure decreasing while volume remains constant. When the pressure within the left ventricular model decreases to less than the pressure in the left atrium, the mitral valve simulator opens, entering the filling phase. The pulsatile pump continues to draw fluid out of the first chamber, and the left ventricular model continues to relax until the filling process is complete. Figure 10A (As shown in the diagram at the end of the filling phase), the mitral valve simulator is turned off.

[0055] Figure 10BThis is a schematic diagram illustrating the shape change of the left ventricular model when afterload decreases according to an embodiment of the present invention. Compared to the normal pulsating state, when the afterload of the in vitro testing system decreases, the left ventricular model requires less intraventricular pressure to overcome the aortic pressure during contraction. The amount of contraction in the thickness of the left ventricular model at the end of isovolumetric contraction and at the end of ejection is reduced compared to the normal state, resulting in increased thickness. This leads to a decrease in the volume of the left ventricular at the end of ejection, an increase in left ventricular stroke volume, and an increase in cardiac output. This can simulate the reduced ventricular afterload and increased cardiac output during aortic ventricular assist device intervention, improving perfusion of peripheral organs such as the kidneys.

[0056] Figure 10C This is a schematic diagram illustrating the shape changes of the left ventricular model when preload is reduced according to an embodiment of the present invention. Compared to the normal beating state, when the preload of the in vitro testing system is reduced, the left ventricular model requires lower pressure within the ventricle to complete filling during diastole. The thickness of the left ventricular model increases at the end of isovolumetric relaxation and at the end of filling compared to the normal state, resulting in a smaller fluid volume within the left ventricle at the end of filling, a decrease in left ventricular stroke volume, and a decrease in cardiac output. This can simulate the reduced output of the native heart after preload reduction during transaortic valve interventional pump assistance, allowing the native heart to rest and facilitating ventricular remodeling to aid myocardial recovery.

[0057] This invention also provides a method for in vitro testing of interventional left ventricular assist devices using the above-described in vitro testing system, the method comprising: S1: Adjust the control parameters so that the heart rate, cardiac output, aortic blood pressure and arterial branch flow signals of the test system conform to the hemodynamic parameters under specific heart failure conditions, and record them as baseline data; This invention, through adjusting control parameters, enables the circulatory loop system to meet the hemodynamic parameters of a specific heart failure state. Specifically, by adjusting the operating parameters of the pulse pump, such as frequency, stroke volume, and systolic-diastolic time ratio, the systolic and diastolic movements of the left and right ventricular models are driven to simulate the cardiac function of a specific heart failure patient. Then, the electric throttle valve and pressure controller are adjusted to ensure that the preload and afterload of the left ventricular model conform to the hemodynamic characteristics of a heart failure patient. Finally, the manual throttle valve is fine-tuned to ensure that the cardiac output and the fluid flow ratio of each branch of the artery conform to physiological characteristics.

[0058] S2: The interventional left ventricular assist device is delivered via a sheath to the descending aorta or the transaortic valve location through a vascular interventional pathway at the femoral artery location; Once the circulatory system meets the hemodynamic characteristics of a heart failure patient, the first and second pulsatile pumps operate continuously, while the pressure controller is shut off to prevent external influences on the circulatory system. The interventional left ventricular assist device is delivered via a delivery sheath through a pre-reserved vascular access point at the femoral artery and deployed above the renal artery or across the aortic valve.

[0059] S3: Activate the left ventricular assist device, measure cardiac output, pressure and flow signals of the aorta and its branches under preset conditions, and record them as experimental data; The ventricular assist device operates according to preset conditions. Changes in the fluid dynamic parameters of the circulatory loop system are measured during the operation of the ventricular assist device, including pressure data of each module, ascending aorta pressure, descending aorta pressure, renal artery pressure data, as well as cardiac output, brachiocephalic trunk, left common carotid artery, left subclavian artery flow and renal artery flow data, which are recorded as experimental data.

[0060] S4: Compare experimental data with baseline data to evaluate the impact of ventricular assist devices on cardiac output, cerebral and renal perfusion flow under preset operating conditions; This invention compares experimental data with baseline data to evaluate the impact of a ventricular assist device on cardiac output under preset operating conditions, and assesses the impact on cerebral and renal blood perfusion during device operation by measuring changes in flow in the brachiocephalic trunk, left common carotid artery, left subclavian artery, and renal artery.

[0061] S5: By changing baseline data and ventricular assist device operating conditions, evaluate the hemodynamic performance of the ventricular assist device under different heart failure states and operating conditions.

[0062] The embodiments of the present invention can test the impact of ventricular assist devices on the circulatory system under different operating conditions based on the characteristics of the circulatory system of different heart failure patients, thereby comprehensively analyzing the safety and effectiveness of ventricular assist devices, providing a basis for device structural optimization, and providing guidance for animal experiments and product optimization.

[0063] This invention can be used for in vitro testing of transvalvular interventional ventricular assist devices (such as axial flow pumps similar to Impella or pulsatile pumps of iVAC2L) and aortic intraventricular assist devices (such as aortic balloon counterpulsation pumps and intra-aortic axial flow pumps (Aortix and ModulHeart)). Figure 11 This is a schematic diagram of an in vitro test of the interventional pump 4 used across the aortic valve according to an embodiment of the present invention. The present invention can test the deload effect of the interventional pump 4 on the native heart during operation. Figure 12 This is a schematic diagram of an in vitro test of a modular intra-aortic axial flow pump 5 according to an embodiment of the present invention. The present invention can test the effect of intra-aortic axial flow pump on brain and kidney perfusion flow during operation, and can measure the change in cardiac output of the native heart. Figure 13 This is a schematic diagram of an in vitro test of the intra-aortic counterpulsation pump 6 according to an embodiment of the present invention.

[0064] The present invention has the following beneficial effects: 1. This invention uses a ventricular model made of three layers of flexible material to simulate the elastic deformation of the ventricular wall during contraction and relaxation, thereby simulating the effect of preload and afterload changes on cardiac output during the operation of the ventricular assist device. 2. This invention has a biomimetic aortic vascular model, which can evaluate the impact of ventricular assist device operation on carotid and renal artery flow.

[0065] The above description describes the preferred embodiments of the present invention and the technical principles applied thereto. For those skilled in the art, any obvious changes such as equivalent transformations or simple substitutions based on the technical solutions of the present invention, without departing from the spirit and scope of the present invention, shall fall within the protection scope of the present invention.

Claims

1. An in vitro testing system for an interventional left ventricular assist device, characterized in that, It includes a circulating loop system, a control system, and a data acquisition system, among which, The circulatory loop system includes a left ventricular module, a mitral valve simulator, an aortic valve simulator, an artery module, a vein module, a right atrium module, a right ventricular module, a tricuspid valve simulator, a pulmonary valve simulator, a pulmonary vessel module, a left atrium module, and an electric throttle valve. The modules are connected by silicone tubing to simulate the directional flow of blood driven by the heart in the human circulatory system. The control system includes a host computer and a controller. The controller includes a ventricular drive control module, a gas supply control module, and an electric throttle valve control module. By adjusting the control parameters, the hemodynamic characteristics of the circulatory system under different heart failure states are simulated. The data acquisition system includes a pressure sensor and a flow sensor, which measure the pressure and flow signals at different preset points in the circulatory system. The data acquisition system communicates with a host computer to evaluate the hemodynamic state of the circulatory system in real time.

2. The in vitro testing system for the interventional left ventricular assist device according to claim 1, characterized in that, The left ventricular module includes a first pulsatile pump, a first chamber, and a left ventricular model, used to simulate the pumping of blood by the left ventricle; The arterial blood vessel module includes an aortic blood vessel model, a manual throttle valve, and a collection chamber. The aortic blood vessel inlet is connected to the outlet of the left ventricular module, flowing to different branch arteries. After being collected through multiple collection chambers, it connects to the venous module. The venous module includes a second chamber and a pressure controller, which regulates the pressure and compliance of the main venous system by changing the gas pressure above the liquid surface in the second chamber. The right atrial module includes a third chamber and a first bellows assembly. The inlet of the third chamber is connected to the venous module, and the outlet is connected to the right ventricular model. The filling of the right atrium is simulated by the volume change of the bellows. The right ventricular module includes a second pulsatile pump, a fourth chamber, and a right ventricular model. The fourth chamber is connected to the right atrium via a tricuspid valve simulator and to the pulmonary vascular module via a pulmonary valve simulator. It is used to simulate the directional pumping function of the right ventricle and pump blood from the right atrium to the pulmonary vascular module. The pulmonary vascular module includes a fifth chamber and a second corrugated tube assembly. The inlet of the fifth chamber is connected to the right ventricular module and the outlet is connected to the left atrial module. The second corrugated tube assembly simulates the compliance of the pulmonary vascular system. The left atrial module includes a sixth chamber and a third corrugated tube assembly, which is connected upstream to the pulmonary vascular module and downstream to the left ventricular module. The filling of the left atrium is simulated by the volume change of the third corrugated tube assembly.

3. The in vitro testing system for the interventional left ventricular assist device according to claim 2, characterized in that, The right ventricular module has the same structure as the left ventricular module; the first chamber of the left ventricular module is connected to the left atrium via a mitral valve simulator, to the arterial blood vessel module via an aortic valve simulator, and to the first pulsating pump via a pagoda connector; the left ventricular model is placed in the first chamber, and pure water is filled between the left ventricular model and the first chamber. The pulsating flow generated by the pulsating pump changes the volume of pure water in the first chamber, thereby driving the contraction and relaxation of the left ventricular model; a water filling valve and a venting valve are provided at the top of the first chamber for filling with pure water.

4. The in vitro testing system for the interventional left ventricular assist device according to claim 3, characterized in that, The left ventricular model comprises three layers of flexible material: an inner wall, a middle layer, and an outer wall. The inner wall material is smooth and simulates the endocardium, the middle layer simulates the myocardium, and the outer wall is used to withstand the driving pressure of pure water. The elastic modulus of the inner wall, middle layer, and outer wall materials of the ventricular model decreases sequentially. The middle layer material is relatively thick, and its elastic deformation in the thickness direction is large during left ventricular pulsation, which can reflect the influence of ventricular preload and afterload changes on ventricular volume. The thickness of the inner wall material is 0.5-2 mm, the thickness of the middle layer material is 8-11 mm, and the thickness of the outer wall material is 0.5-1 mm.

5. The in vitro testing system for the interventional left ventricular assist device according to claim 4, wherein the right ventricular model has the same structure as the left ventricular model; the inner wall material of the right ventricular model has a thickness of 0.5-1 mm, the middle layer material has a thickness of 3-4 mm, and the outer wall material has a thickness of 0.2-0.6 mm.

6. The in vitro testing system for the interventional left ventricular assist device according to claim 2, characterized in that, The aortic valve is a bioprosthetic valve or a polymer valve with the same shape as the human aortic valve; the mitral valve simulator, tricuspid valve simulator and pulmonary valve simulator are ordinary tubular check valves, or mechanical valves, bioprosthetic valves or polymer valves.

7. The in vitro testing system for the interventional left ventricular assist device according to claim 2, characterized in that, The aortic vessel model includes the common carotid artery, vertebral artery, axillary artery, celiac trunk artery, superior mesenteric artery, renal artery, inferior mesenteric artery, internal iliac artery, and femoral artery. It is made of biomimetic silicone material and has compliance similar to that of native arteries. The femoral artery is equipped with a vascular interventional pathway for the delivery of interventional ventricular assist devices.

8. The in vitro testing system for the interventional left ventricular assist device according to claim 2, characterized in that, The fluid collection cavities include a cerebral fluid collection cavity, an upper limb fluid collection cavity, an abdominal fluid collection cavity, and a lower limb fluid collection cavity; the cerebral fluid collection cavity is connected to the common carotid artery and the vertebral artery; the upper limb fluid collection cavity is connected to the axillary artery; the abdominal fluid collection cavity is connected to the celiac trunk artery, the superior mesenteric artery, and the renal artery; the lower limb fluid collection cavity is connected to the inferior mesenteric artery, the internal iliac artery, and the femoral artery; the fluid collection cavities collect arterial branches and then connect to the venous module.

9. The in vitro testing system for the interventional left ventricular assist device according to claim 2, characterized in that, The electric throttle valve is installed between the fluid collection chamber and the venous module to adjust systemic circulation resistance; the pipelines of the pulmonary vascular module and the left atrial module are also equipped with electric throttle valves to simulate pulmonary circulation resistance; the manual throttle valve is installed in each branch of the arterial blood vessel to regulate the flow distribution of different blood vessel branches.

10. The in vitro testing system for the interventional left ventricular assist device according to claim 2, characterized in that, The top of the vein module is equipped with a filling valve and a pneumatic interface. The filling valve is used to inject test liquid into the entire circulation system, and the pneumatic interface is connected to a pressure controller to control the pressure in the vein cavity. The test liquid is animal blood or a water-glycerol mixture.

11. The in vitro testing system for the interventional left ventricular assist device according to claim 1, characterized in that, The ventricular drive control module can drive the first and second pulse pumps to generate biomimetic pulsating blood flow according to different frequencies, stroke volume, and systolic-diastolic ratios, periodically changing the volume of pure water in the cavity to drive ventricular contraction and relaxation; the gas supply control module adjusts the pressure and compliance of the second closed cavity of the venous module through a pressure controller; the electric throttle valve control module changes the preload and afterload of the circulatory system by adjusting the opening of the throttle valve.

12. A method for conducting in vitro testing of an interventional left ventricular assist device using the testing system described in any one of claims 1-11, characterized in that, The method includes the following steps: (1) Adjust the control parameters so that the heart rate, cardiac output, aortic blood pressure and arterial branch flow signals of the test system are consistent with the hemodynamic parameters under a specific heart failure state, and record them as baseline data; (2) The interventional left ventricular assist device is delivered via a sheath to the descending aorta or the location across the aortic valve through a vascular interventional pathway at the femoral artery location; (3) Activate the left ventricular assist device, measure the cardiac output, pressure and flow signals of the aorta and branch arteries under the preset working conditions, and record them as experimental data; (4) Compare experimental data with baseline data to evaluate the effects of the ventricular assist device on cardiac output, brain and kidney perfusion pressure and flow rate under preset operating conditions; (5) Change the baseline data and the operating conditions of the ventricular assist device to evaluate the hemodynamic performance of the ventricular assist device under different heart failure states and different operating conditions.

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