A need exists for a mock circulation that behaves in a physiologic manner for testing cardiac devices in normal and pathologic states. To address this need, an integrated mock cardiovascular system consisting of an atrium, ventricle, and systemic and coronary vasculature was developed specifically for testing ventricular assist devices (VADs). This test configuration enables atrial or ventricular apex inflow and aortic outflow cannulation connections. The objective of this study was to assess the ability of the mock ventricle to mimic the Frank-Starling response of normal, heart failure, and cardiac recovery conditions. The pressure-volume relationship of the mock ventricle was evaluated by varying ventricular volume over a wide range via atrial (preload) and aortic (afterload) occlusions. The input impedance of the mock vasculature was calculated using aortic pressure and flow measurements and also was used to estimate resistance, compliance, and inertial mechanical properties of the circulatory system. Results demonstrated that the mock ventricle pressure-volume loops and the end diastolic and end systolic pressure-volume relationships are representative of the Starling characteristics of the natural heart for each of the test conditions. The mock vasculature can be configured to mimic the input impedance and mechanical properties of native vasculature in the normal state. Although mock circulation testing systems cannot replace in vivo models, this configuration should be well suited for developing experimental protocols, testing device feedback control algorithms, investigating flow profiles, and training surgical staff on the operational procedures of cardiovascular devices.

Rotary blood pumps (RBPs) are currently being used as a bridge to transplantation as well as for myocardial recovery and destination therapy for patients with heart failure. Physiologic control systems for RBPs that can automatically and autonomously adjust the pump flow to match the physiologic requirement of the patient are needed to reduce human intervention and error, while improving the quality of life. Physiologic control systems for RBPs should ensure adequate perfusion while avoiding inflow occlusion via left ventricular (LV) suction for varying clinical and physical activity conditions. For RBPs used as left ventricular assist devices (LVADs), we hypothesize that maintaining a constant average pressure difference between the pulmonary vein and the aorta (deltaPa) would give rise to a physiologically adequate perfusion while avoiding LV suction. Using a mock circulatory system, we tested the performance of the control strategy of maintaining a constant average deltaPa and compared it with the results obtained when a constant average pump pressure head (deltaP) and constant rpm are maintained. The comparison was made for normal, failing, and asystolic left heart during rest and at light exercise. The deltaPa was maintained at 95 +/- 1 mm Hg for all the scenarios. The results indicate that the deltaPa control strategy maintained or restored the total flow rate to that of the physiologically normal heart during rest (3.8 L/m) and light exercise (5.4 L/m) conditions. The deltaPa approach adapted to changing exercise and clinical conditions better than the constant rpm and constant deltaP control strategies. The deltaPa control strategy requires the implantation of two pressure sensors, which may not be clinically feasible. Sensorless RBP control using the deltaPa algorithm, which can eliminate the failure prone pressure sensors, is being currently investigated.

This study investigated the hemodynamic and left ventricular (LV) pressure-volume loop responses to continuous versus pulsatile assist techniques at 50% and 100% bypass flow rates during simulated ventricular pathophysiologic states (normal, failing, recovery) with Starling response behavior in an adult mock circulation. The rationale for this approach was the desire to conduct a preliminary investigation in a well controlled environment that cannot be as easily produced in an animal model or clinical setting. Continuous and pulsatile flow ventricular assist devices (VADs) were connected to ventricular apical and aortic root return cannulae. The mock circulation was instrumented with a pressure-volume conductance catheter for simultaneous measurement of aortic root pressure and LV pressure and volume; a left atrial pressure catheter; a distal aortic pressure catheter; and aortic root, aortic distal, VAD output, and coronary flow probes. Filling pressures (mean left atrial and LV end diastolic) were reduced with each assist technique; continuous assist reduced filling pressures by 50% more than pulsatile. This reduction, however, was at the expense of a higher mean distal aortic pressure and lower diastolic to systolic coronary artery flow ratio. At full bypass flow (100%) for both assist devices, there was a pronounced effect on hemodynamic parameters, whereas the lesser bypass flow (50%) had only a slight influence. Hemodynamic responses to continuous and pulsatile assist during simulated heart failure differed from normal and recovery states. These findings suggest the potential for differences in endocardial perfusion between assist techniques that may warrant further investigation in an in vivo model, the need for controlling the amount of bypass flow, and the importance in considering the choice of in vivo model.

Ventricular assist devices (VADs) have been used successfully as a bridge to transplant in heart failure patients by unloading ventricular volume and restoring the circulation. In a few cases, patients have been successfully weaned from these devices after myocardial recovery. To promote myocardial recovery and alleviate the demand for donor organs, we are developing an artificial vasculature device (AVD) that is designed to allow the heart to fill to its normal volume but eject against a lower afterload. Using this approach, the heart ejects its stroke volume (SV) into an AVD anastomosed to the aortic arch, which has been programmed to produce any desired afterload condition defined by an input impedance profile. During diastole, the AVD returns this SV to the aorta, providing counterpulsation. Dynamic computer models of each of the assist devices (AVD, continuous, and pulsatile flow pumps) were developed and coupled to a model of the cardiovascular system. Computer simulations of these assist techniques were conducted to predict physiologic responses. Hemodynamic parameters, ventricular pressure-volume loops, and vascular impedance characteristics were calculated with AVD, continuous VAD, and asynchronous pulsatile VAD support for a range of clinical cardiac conditions (normal, failing, and recovering left ventricle). These simulation results indicate that the AVD may provide better coronary perfusion, as well as lower vascular resistance and elastance seen by the native heart during ejection compared with continuous and pulsatile VAD. Our working hypothesis is that by controlling afterload using the AVD approach, ventricular cannulation can be eliminated, myocardial perfusion improved, myocardial compliance and resistance restored, and effective weaning protocols developed that promote myocardial recovery.

Although continuous flow (CF) and pulsatile flow (PF) ventricular assist devices (VADs) are being clinically used, their effects on aortic blood flow, as a measure of overall blood distribution, remain unclear. In acute VAD support animal experiments, our group has described a zone of turbulent mixing in the aortic arch. The objective of this study was to confirm this finding in the controlled setting of an adult mock circulation, simulating ventricular pathophysiologic states (normal and failing ventricle). CF and PF flow VADs were connected to ventricular apical inflow and ascending aorta (AA) or descending aorta (DA) outflow cannulae. Cardiovascular pressure and flow waveforms were recorded at varying levels of VAD bypass resulting in four test conditions: (i) CF-AA; (ii) CF-DA; (iii) PF-AA; and (iv) PF-DA. Confirming the animal data, no differences in mean aortic flow between CF and PF VADs were found, and significantly lower mean aortic arch flow with DA cannulation was noted. Mean aortic root flow decreased with increasing VAD bypass flow. As in the animal studies, despite similar mean flow rates, significant differences in waveform morphology were observed for AA and DA outflow graft locations and varying levels of VAD bypass. At 100% VAD support in the failing heart, PF restored waveform pulsatility to normal baseline while CF resulted in little pulsatility. These results confirm our earlier findings in the animal model, suggesting that outflow graft location may have a significant effect on aortic blood flow distribution. The long-term implications of these findings are being examined in ongoing studies.

Rotary blood pumps (RBP) are currently being used as a bridge to transplantation as well as for myocardial recovery and destination therapy for patients with heart failure. Physiologic control systems for RBP that can automatically and autonomously adjust the pump flow to match the physiologic requirement of the patient while avoiding suction for varying clinical and physical activity conditions are needed to reduce human intervention and error, and to improve the quality of life. For RBP used as left ventricular assist devices (LVAD), we hypothesize that maintaining a constant average pressure difference between the pulmonary vein and the aorta (∆P a) or maintaining a constant average pressure difference between the left ventricle and the aorta (∆P ) would give rise to a physiologically adequate perfusion while avoiding LV suction. Using a mock circulatory system we tested the performance of the control strategy of maintaining a constant average ∆P a and a constant average pump pressure head (∆P ) and compared it with the results obtained when constant rpm is maintained. The comparison was made for normal, failing, and asystolic left heart during rest and at light exercise. The ∆P a was maintained at 95 ± 1 mmHg and ∆P was maintained at 75 ± 1 mmHg for all the scenarios. The results indicate that the ∆P a control strategy maintained or restored the total flow rate to that of the physiologically normal heart during rest (3.8 l/m) and light exercise (5.4 l/m) conditions. The ∆P a approach adapted to changing exercise and clinical conditions better than the constant rpm and constant ∆P control strategies. Our computer simulation studies indicate that the ∆P control strategy performs better than the constant rpm control strategy, especially at higher cardiac demand situations, which could not be tested experimentally due to the limitation of the mock circulatory system.

A mock circulation system has been developed to approximate key anatomic features and simulate the pressures and flows of an infant. Pulsatile flow is generated by 10 cc pulsatile ventricles (Utah infant ventricular assist device). Systemic vasculature is mimicked through the use of 3/8" ID bypass tubing with two flexible reservoirs to provide compliance. Vascular resistance, including pulmonary, aortic, and major branches, is controlled via a series of variable pinch clamps. The coronary branch has a dynamic resistor so that the majority of flow occurs during diastole. The system is instrumented to measure key pressures and flows. Right atrial pressure, left atrial pressure, pulmonary artery pressure, and mean aortic pressure are measured with high-fidelity pressure catheters (Millar Instruments, Houston, TX). Flows are measured by transit time ultrasonic flow probes (Transonic Systems, Ithaca, NY) in the pulmonary artery, aorta, coronary artery, and brachiocephalic artery along with assist device flow. The system can be tuned to create the hemodynamic values of a pediatric patient under normal or heart failure conditions. Once tuned to the desired hemodynamic conditions, the loop may be used to test the performance of various circulatory support systems including the intra-aortic balloon pump, left and right ventricular assist devices, or cardiopulmonary support systems such as extracorporeal membrane oxygenation.

OBJECTIVE Despite progress with adult ventricular assist devices (VADs), limited options exist to support pediatric patients with life-threatening heart disease. Extracorporeal membrane oxygenation (ECMO) remains the clinical standard. To characterize (patho)physiologic responses to different modes of mechanical unloading of the failing pediatric heart, ECMO was compared to either intraaortic balloon pump (IABP), pulsatile-flow (PF)VAD, or continuous-flow (CF)VAD support in a pediatric heart failure model. DESIGN Experimental. SETTING Large animal laboratory operating room. SUBJECTS Yorkshire piglets (n=47, 11.7±2.6 kg). INTERVENTIONS In piglets with coronary ligation-induced cardiac dysfunction, mechanical circulatory support devices were implanted and studied during maximum support. MEASUREMENTS and MAIN RESULTS Left ventricular, right ventricular, coronary, carotid, systemic arterial, and pulmonary arterial hemodynamics were measured with pressure and flow transducers. Myocardial oxygen consumption and total-body oxygen consumption (VO2) were calculated from arterial, venous, and coronary sinus blood sampling. Blood flow was measured in 17 organs with microspheres. Paired student t-tests compared baseline and heart failure conditions. One-way repeated-measures ANOVA compared heart failure, device support mode(s), and ECMO. Statistically significant (p<0.05) findings included: 1) improved left ventricular blood supply/demand ratio during PFVAD, CFVAD, and ECMO but not IABP support, 2) improved global myocardial blood supply/demand ratio during PFVAD, and CFVAD but not IABP or ECMO support, and 3) diminished pulsatility during ECMO and CFVAD but not IABP and PFVAD support. A profile of systems-based responses was established for each type of support. CONCLUSIONS Each type of pediatric VAD provided hemodynamic support by unloading the heart with a different mechanism that created a unique profile of physiological changes. These data contribute novel, clinically relevant insight into pediatric mechanical circulatory support and establish an important resource for pediatric device development and patient selection.