MODERNIZATION OF THE MOCK CIRCULATORY LOOP: ADVANCED PHYSICAL MODELING, HIGH PERFORMANCE HARDWARE, AND INCORPORATION OF ANATOMICAL MODELS

A systemic mock circulatory loop plays a pivotal role as the in vitro assessment tool for left heart medical devices. The standard design employed by many research groups dates to the early 1970\u27s, and lacks the acuity needed for the advanced device designs currently being explored. The necessity to update the architecture of this in vitro tool has become apparent as the historical design fails to deliver the performance needed to simulate conditions and events that have been clinically identified as challenges for future device designs. In order to appropriately deliver the testing solution needed, a comprehensive evaluation of the functionality demanded must be understood. The resulting system is a fully automated systemic mock circulatory loop, inclusive of anatomical geometries at critical flow sections, and accompanying software tools to execute precise investigations of cardiac device performance. Delivering this complete testing solution will be achieved through three research aims: (1) Utilization of advanced physical modeling tools to develop a high fidelity computational model of the in vitro system. This model will enable control design of the logic that will govern the in vitro actuators, allow experimental settings to be evaluated prior to execution in the mock circulatory loop, and determination of system settings that replicate clinical patient data. (2) Deployment of a fully automated mock circulatory loop that allows for runtime control of all the settings needed to appropriately construct the conditions of interest. It is essential that the system is able to change set point on the fly; simulation of cardiovascular dynamics and event sequences require this functionality. The robustness of an automated system with incorporated closed loop control logic yields a mock circulatory loop with excellent reproducibility, which is essential for effective device evaluation. (3) Incorporating anatomical geometry at the critical device interfaces; ascending aorta and left atrium. These anatomies represent complex shapes; the flows present in these sections are complex and greatly affect device performance. Increasing the fidelity of the local flow fields at these interfaces delivers a more accurate representation of the device performance in vivo

Development of a physiologic ex vivo vessel perfusion system.

Introduction: Over time, continuous flow ventricular assist devices (VADs) have become the primary form of implanted mechanical circulatory support (MCS) due to their smaller size, higher energy efficiency, longer durability, and fewer LVAD-related complications when compared to pulsatile flow VADs. However, continuous and pulsatile flows may elicit different cellular and tissue response, particularly in the arterial vasculature, which could have a profound impact on the future operation of MCS devices. Therefore, a unique ex vivo perfusion system integrated with a mock adult circulatory system was design to study the impact of VAD-generated flow patterns on vascular function. Methods: The benefits of a mock circulatory loop and an ex vivo perfusion system were combined by designing and integrating a vessel perfusion chamber to an adult-sized mock circulatory loop as a parallel flow branch distal to VAD outflow. Testing was conducted using a mock over several physiologic conditions (normal, heart failure, and hypertension) and at various levels of VAD flow. The system was integrated into an incubator to allow for control of pH and temperature in future studies and fitted with a vessel for feasibility testing. Data was collected using a custom Labview program and analyzed using the HEART program, an automated beat-to-beat cardiovascular analysis program based in Matlab. Results: The chamber was successfully fabricated and installed in the mock circulatory system, allowing for perfusion and longitudinal stretching of bovine carotid arteries. The waveforms and values for pressures and flows created in the mock loop were similar to physiologic values under each tested condition. Under normal hemodynamic conditions (CO = 4.5 L/min, MAP = 91 mmHg) perfusion chamber flow was 0.51 L/min, while under HF conditions (CO = 3.3 L/min, MAP = 81 mmHg) it was reduced to 0.18 L/min, which are representative of in vivo carotid artery hemodynamics. Due to physiologic preloads and afterloads, VAD performance was as would be expected in clinical application. The system was found to be sufficient for future testing with bovine carotid arteries and extended perfusion times (\u3e24 hours). Conclusions: This study resulted in an ex vivo vessel perfusion system that can successfully expose bovine carotid arteries to physiologic and VAD-specific hemodynamic waveforms. The ability to combine the mock ventricle with clinically implanted VADs makes this system both unique and clinically relevant for studying the effects of continuous versus pulsatile flow on the peripheral vasculature

Structure and motion design of a mock circulatory test rig

Mock circulatory test rig (MCTR) is the essential and indispensable facility in the cardiovascular in vitro studies. The system configuration and the motion profile of the MCTR design directly influence the validity, precision, and accuracy of the experimental data collected. Previous studies gave the schematic but never describe the structure and motion design details of the MCTRs used, which makes comparison of the experimental data reported by different research groups plausible but not fully convincing. This article presents the detailed structure and motion design of a sophisticated MCTR system, and examines the important issues such as the determination of the ventricular motion waveform, modelling of the physiological impedance, etc., in the MCTR designing. The study demonstrates the overall design procedures from the system conception, cardiac model devising, motion planning, to the motor and accessories selection. This can be used as a reference to aid researchers in the design and construction of their own in-house MCTRs for cardiovascular studies

Cavopulmonary Support for Failing Fontan Patients: Computational and In Vitro Assessment

Congenital heart defects are responsible for the mortality of approximately 300,000 newborn each year. One study in 2010 estimated that over 2 million patients were living with congenital heart defects in the United States. Congenital heart defects have the highest hospitalization cost among other birth defect categories. The damage on the U.S economy in 2013 was estimated $6.1 billion. The most complex and severe form of these defects results in single ventricle physiology. Fortunately, over the last 50 years, these patients have been able to survive into adulthood as a result of three stages of surgeries culminating with Fontan operation. However, Fontan operation as the current ultimate palliation of single ventricle defects results in significant late complications. Fontan patients will eventually develop circulatory failure and are in desperate need of an immediate therapeutic solution. A rightsided device surgically placed in the cavopulmonary pathway could technically substitute the missing sub-pulmonary ventricle by generating a mild pressure boost. However, currently, there is no device specifically designed for this application due to the small market size. On the other hand, off-label use of an arterial pump (originally designed for left side application) for the cavopulmonary support remains challenging. This is because the hemodynamic impact of a ventricular assist device (VAD) implanted on the right circulation of a Fontan patient is not yet clear. Moreover, further research is needed to identify the physiological consequences of two clinically-considered surgical configurations (IVC and full assisted configurations) for the cavopulmonary VAD installation, with full and IVC support corresponding to the entire venous return or only the inferior venous return, respectively, being routed through the VAD. First objective of this thesis is surgical planning to accurately predict the outcome of cavopulmonary support in failing Fontan patients and findings of this study will help the surgeons in developing coherent clinical strategies for the cavopulmonary support implementation and tuning. Specific objective 2 will investigate the desired operating region for designing a cavopulmonary blood pump that can offer a promising alternative treatment option for a wide range of failing Fontan patients

Mock circulatory loop applications for testing cardiovascular assist devices and in vitro studies

The mock circulatory loop (MCL) is an in vitro experimental system that can provide continuous pulsatile flows and simulate different physiological or pathological parameters of the human circulation system. It is of great significance for testing cardiovascular assist device (CAD), which is a type of clinical instrument used to treat cardiovascular disease and alleviate the dilemma of insufficient donor hearts. The MCL installed with different types of CADs can simulate specific conditions of clinical surgery for evaluating the effectiveness and reliability of those CADs under the repeated performance tests and reliability tests. Also, patient-specific cardiovascular models can be employed in the circulation of MCL for targeted pathological study associated with hemodynamics. Therefore, The MCL system has various combinations of different functional units according to its richful applications, which are comprehensively reviewed in the current work. Four types of CADs including prosthetic heart valve (PHV), ventricular assist device (VAD), total artificial heart (TAH) and intra-aortic balloon pump (IABP) applied in MCL experiments are documented and compared in detail. Moreover, MCLs with more complicated structures for achieving advanced functions are further introduced, such as MCL for the pediatric application, MCL with anatomical phantoms and MCL synchronizing multiple circulation systems. By reviewing the constructions and functions of available MCLs, the features of MCLs for different applications are summarized, and directions of developing the MCLs are suggested

Flow Dynamics in Cardiovascular Devices: A Comprehensive Review

This review explores flow dynamics in cardiovascular devices, focusing on fundamental fluid mechanics principles and normal blood flow patterns. It discusses the role of different structures in maintaining flow dynamics and the importance of stents, heart valves, artificial hearts, and ventricular assist devices in cardiovascular interventions. The review emphasizes the need for optimized designs and further research to enhance knowledge of flow dynamics in cardiovascular devices, advancing the field and improving patient care in cardiovascular interventions

Initial clinical validation of a hybrid in silico—in vitro cardiorespiratory simulator for comprehensive testing of mechanical circulatory support systems

Simulators are expected to assume a prominent role in the process of design—development and testing of cardiovascular medical devices. For this purpose, simulators should capture the complexity of human cardiorespiratory physiology in a realistic way. High fidelity simulations of pathophysiology do not only allow to test the medical device itself, but also to advance practically relevant monitoring and control features while the device acts under realistic conditions. We propose a physiologically controlled cardiorespiratory simulator developed in a mixed in silico-in vitro simulation environment. As inherent to this approach, most of the physiological model complexity is implemented in silico while the in vitro system acts as an interface to connect a medical device. As case scenarios, severe heart failure was modeled, at rest and at exercise and as medical device a left ventricular assist device (LVAD) was connected to the simulator. As initial validation, the simulator output was compared against clinical data from chronic heart failure patients supported by an LVAD, that underwent different levels of exercise tests with concomitant increase in LVAD speed. Simulations were conducted reproducing the same protocol as applied in patients, in terms of exercise intensity and related LVAD speed titration. Results show that the simulator allows to capture the principal parameters of the main adaptative cardiovascular and respiratory processes within the human body occurring from rest to exercise. The simulated functional interaction with the LVAD is comparable to the one clinically observed concerning ventricular unloading, cardiac output, and pump flow. Overall, the proposed simulation system offers a high fidelity in silico-in vitro representation of the human cardiorespiratory pathophysiology. It can be used as a test bench to comprehensively analyze the performance of physically connected medical devices simulating clinically realistic, critical scenarios, thus aiding in the future the development of physiologically responding, patient-adjustable medical devices. Further validation studies will be conducted to assess the performance of the simulator in other pathophysiological conditions

From Benchtop to Beside: Patient-specific Outcomes Explained by Invitro Experiment

Study: Recent analyses show that females have higher early postoperative (PO) mortality and right ventricular failure (RVF) than males after left ventricular assist device (LVAD) implantation; and that this association is partially mediated by smaller LV size in females. Benchtop experiments allow us to investigate patient-specific (PS) characteristics in a reproducible way given the fact that the PS anatomy and physiology is mimicked accurately. With multiple heart models of varying LV size, we can directly study the individual effects of titrating the LVAD speed and the resulting bi-ventricular volumes, shedding light on the interplay between LV and RV as well as resulting inter-ventricular septum (IVS) positions, which may cause the different outcomes pertaining to sex. Methods: In vitro, we studied the impact of the heart size to IVS position using two smaller and two larger sized PS silicone heart phantoms derived from clinical CT images (Fig. 1A). With ultrasound crystals that were integrated on a placeholder inflow cannula, the IVS position was measured during LV and RV volume changes (dV) mimicking varying ventricular loading states (Fig. 1B). Figure 1 A Two small (blue) and two large PS heart phantoms (orange) on B benchtop. C Median septum curvature results. LVEDD/LVV/RVV: LV enddiastolic diameter/LV and RV volume. Results: Going from small to large dV, at zero curvature, the septum starts to shift towards the left; for smaller hearts at dV = -40 mL and for larger hearts at dV = -50 mL (Fig. 1C). This result indicates that smaller hearts are more prone to an IVS shift to the left than larger hearts. We conclude that smaller LV size may therefore mediate increased early PO LVAD mortality and RVF observed in females compared to males. Novel 3D silicone printing technology enables us to study accurate, PS heart models across a heterogeneous patient population. PS relationships can be studied simultaneously to clinical assessments and support the decision-making prior to LVAD implantation