Current ventricular assist devices (VADs) are rotary blood pumps used to treat end-stage heart failure. VADs are operated at a constant speed that is manually adjusted by a clinician based on the patient's cardiac demand during routine medical examinations. VADs operated at a constant speed have inadequate passive flow regulation due to the inherent mechanical pressure-flow characteristics of the pump; this can lead to harmful situations where the VAD is overpumping or underpumping. Typically, patients on long-term VAD support are discharged to an outpatient setting where the VAD speed can remain the same for weeks or months at a time, impacting patient safety and quality of life. Previously, physiological controllers for VADs have been proposed, which automatically adjust VAD speed to meet patient cardiac demand. Clinical implementation of physiological control is currently hindered by the lack of clinically available, implantable, and continuous hemodynamic sensors. This study describes the physiological control of a VAD using a fiber Bragg grating (FBG) sensor previously developed for measuring VAD inlet pressure. The FBG sensor was used as a feedback to a Starling-like physiological controller, and the control quality was compared against the same controller with feedback from a nonimplantable industrial pressure sensor (Omega sensor). Experiments were conducted in a bench-top cardiovascular simulator under various simulated patient scenarios. The average steady-state difference in VAD flow across all experiments was 0.1 L/min with a maximum difference of -0.4 L/min. Similarly, the average steady-state difference in left ventricular end-diastolic pressure was 0.02 mmHg with a maximum difference of -0.2 mmHg. The clinically insignificant differences found between the two feedback methods indicate that the FBG pressure sensor is viable for the physiological control of VADs.

Introduction: This review explores the Starling-like physiological control method (SLC) for rotary ventricular assist devices (VADs) for severe heart failure. The SLC, based on mathematical models of the circulation, has two functions modeling each ventricle. The first function controls the output of the VAD to the arterial pool according to Starling's law, while the second function accounts for how the blood returns to the heart from the veins. The article aims to expose clinicians to SLC in an accessible and clinically relevant discussion. Areas Covered: The article explores the physiology underlying the controller, its development and how that physiology can be adapted to SLC. Examples of controller performance are demonstrated and discussed using a benchtop model of the cardiovascular system. A discussion of the limitations and criticisms of SLC is presented, followed by a future outlook on the clinical adoption of SLC. Expert Opinion: Due to its simplicity and emulation of the natural cardiac autoregulation, SLC is the superior physiological control method for rotary VADs. However, current technical and regulatory challenges prevent the clinical translation of SLC of VADs. Further technical and regulatory development will enable the clinical translation of SLCs of VADs in the coming years.

Speed regulation of dual left ventricular assist devices (LVADs) as a biventricular assist device (BiVAD) may be complicated by process interactions in a cardiovascular-biventricular assist device (CVS-BiVAD) environment. In this work, a conventional centralized model predictive control (MPC) algorithm that could handle process interactions in a multivariable control problem was modified to cater for the state and time-varying factors of the CVS-BiVAD system as well as to include multiple control objectives. Referred to as the centralized multi-objective model predictive control (CMO-MPC), the scheme's control objectives aim to: a) adapt pump flow rate according to the approximate Frank-Starling (FS) mechanism, b) avoid ventricular suction, and c) avoid vascular congestion. The control performance of the CMO-MPC was benchmarked with two non-centralized control schemes: the constant-speed (CS) control and the standard Frank-Starling like proportional-integral (PI-FS) control under two patient scenarios: exercise and postural change. Simulation results revealed that the CMO-MPC avoided suction and congestion in both patient scenarios as compared to the CS control and the PI-FS control, based on the assumptions made on risks of suction and congestion events. It is therefore proposed that the CMO-MPC should be a safe physiological controller for dual LVADs in the future when reliable pressure and flow sensors become clinically available. (C) 2018 Elsevier Ltd. All rights reserved.

Ventricular assist devices are used to support patients with end-stage heart failure. Many patients on long-term VAD support are treated out-of-hospital where monitoring technology for patients is severely limited; leading to sub-optimal patient management. This paper describes a novel fibre Bragg grating (FBG) pressure sensor which was developed for improved monitoring of patients with ventricular assist devices. The FBG sensor was fabricated in-house and characterised in a circulating heat bath. The FBG pressure sensor demonstrated a sensitivity of -0.0046 nm/mmHg with an accuracy of +/- 0.35 mmHg, a resolution of 0.0019 mmHg and a response time of 89.7 mmHg/s. The high sensitivity and resolution combined with the adequate accuracy exhibited by the FBG sensor demonstrated its potential value of the FBG pressure sensor for monitoring patients with ventricular assist devices. Further investigation into device drift, improved manufacturing, and gas-impermeable biocompatible materials are required to prepare the sensor for pre-clinical trials. Crown Copyright (C) 2019 Published by Elsevier B.V. All rights reserved.

Rotary ventricular assist devices (VADs) operated clinically under constant speed control (CSC) cannot respond adequately to changes in patient cardiac demand, resulting in sub-optimal VAD flow regulation. Starling-like control (SLC) of VADs mimics the healthy ventricular flow regulation and automatically adjusts VAD speed to meet varying patient cardiac demand. The use of a fixed control line (CL - the relationship between ventricular preload and VAD flow) limits the flow regulating capability of the controller, especially in the case of exercise. Adaptive SLC (ASLC) overcomes this limitation by allowing the controller to adapt the CL to meet a diverse range of circulatory conditions. This study evaluated ASLC, SLC and CSC in a biventricular supported mock circulation loop under the simulated conditions of exercise, sleep, fluid loading and systemic hypertension. Each controller was evaluated on its ability to remain within predefined limits of VAD flow, preload, and afterload. The ASLC produced superior cardiac output (CO) during exercise (10.1 L/min) compared to SLC (7.3 L/min) and CSC (6.3 L/min). The ASLC produced favourable haemodynamics during sleep, fluid loading and systemic hypertension and could remain within a predefined haemodynamic range in three out of four simulations, suggesting improved haemodynamic performance over SLC and CSC.

The high cost of ventricular assist devices results in poor cost-effectiveness when used as a short-term bridging solution, thus a low-cost alternative is desirable. The present study aimed to develop an intraventricular balloon pump (IVBP) for short-term circulatory support, and to evaluate the effect of balloon actuation timing on the degree of cardiac support provided to a simulated in vitro severe heart failure (SHF) patient. A silicone IVBP was designed to avoid contact with internal left ventricular (LV) features (ie, papillary muscles, chordae, aortic, and mitral valves) based on LV computed tomography data of 10 SHF patients with dilated cardiomyopathy. The hemodynamic effects of varying balloon inflation and deflation timing parameters (inflation duty [D] and end-inflation point [σ]) were evaluated in a purpose-built systemic mock circulatory loop. Three IVBP actuation timing categories were defined: co-, transitional, and counterpulsation. Compared to the SHF baseline, co-pulsation increased aortic flow from 3.5 to 5.2 L/min, mean arterial pressure from 72.1 to 94.8 mmHg and ejection fraction from 14.4% to 21.5%, while mean left atrial pressure decreased from 14.6 to 10 mmHg. Transitional and counterpulsation resulted in a double ventricular pulse and extended the duration of increased ventricular pressure, potentially impeding diastolic filling and coronary perfusion. This in vitro study showed the IVBP could restore the hemodynamic balance of a simulated SHF patient with dilated cardiomyopathy to healthy levels.

Despite the benefits of mechanical circulatory and respiratory support (MCS), patients undergoing extracorporeal membrane oxygenation (ECMO) and the implantation of ventricular assist devices (VADs) continue to experience high rates of serious and life-threatening complications. These include bleeding, thrombosis, sepsis, multiorgan dysfunction, and death. These complications may be caused by the mechanical support or the underlying critical illness that necessitates its use. Reducing MCS complications remains an important goal for the future uptake of this technology.

Rotary ventricular assist devices (VADs) are less sensitive to preload than the healthy heart, resulting in inadequate flow regulation in response to changes in patient cardiac demand. Starling-like physiological controllers (SLCs) have been developed to automatically regulate VAD flow based on ventricular preload. An SLC consists of a cardiac response curve (CRC) which imposes a nonlinear relationship between VAD flow and ventricular preload, and a venous return line (VRL) which determines the return path of the controller. This study investigates the importance of a physiological VRL in SLC of dual rotary blood pumps for biventricular support. Two experiments were conducted on a physical mock circulation loop (MCL); the first compared an SLC with an angled physiological VRL (SLC-P) against an SLC with a vertical VRL (SLC-V). The second experiment quantified the benefit of a dynamic VRL, represented by a series of specific VRLs, which could adapt to different circulatory states including changes in pulmonary (PVR) and systemic (SVR) vascular resistance versus a fixed physiological VRL which was calculated at rest. In both sets of experiments, the transient controller responses were evaluated through reductions in preload caused by the removal of fluid from the MCL. The SLC-P produced no overshoot or oscillations following step changes in preload, whereas SLC-V produced 0.4 L/min (12.5%) overshoot for both left and right VADs. Additionally, the SLC-V had increased settling time and reduced controller stability as evidenced by transient controller oscillations. The transient results comparing the specific and standard VRLs demonstrated that specific VRL rise times were improved by between 1.2 and 4.7 s ( x ¯ = 3.05 s), while specific VRL settling times were improved by between 2.8 and 16.1 seconds ( x ¯ = 8.38 s) over the standard VRL. This suggests only a minor improvement in controller response time from a dynamic VRL compared to the fixed VRL. These results indicate that the use of a fixed physiologically representative VRL is adequate over a wide variety of physiological conditions.

Rotary blood pumps are used to provide mechanical circulatory support to the failing heart in patients who are ineligible or waiting for a transplant. One of the major challenges when implementing two rotary blood pumps for biventricular support is the difficulty in maintaining pulmonary and systemic circulatory volume balance. In this study, a novel multiobjective neural predictive controller (MONPC) hybridized with a preload-based Frank-Starling-like controller (PFS) has been proposed for a dual rotary blood pump biventricular assist device in two different configurations: PFSL-MONPCR and MONPCL-PFSR. The flow rate of one pump is regulated by PFS as a function of preload, while the other pump is controlled by MONPC, which is intended to meet cardiac demand, avoid pulmonary congestion and ventricular suction. A comparative assessment was performed between the proposed controllers and a Dual Independent Frank-Starling-like control system (DI-FS) as well as a constant speed controller. The numerical simulation results showed that MONPCL-PFSR helped unload the congested left ventricle while maintaining high cardiac output during exercise. In contrast, improper flow regulation by DI-FS has resulted in pulmonary congestion. During blood loss, PFSL-MONPCR delivered the lowest suction risk, as compared to the constant speed mode, which produced negative right ventricular preload. When sensor noise and time delays were introduced in the flow and end-diastolic pressure signals, the proposed controllers were able to respond with adequate robustness during the transition from rest to exercise. This study demonstrated that the proposed controllers are superior in matching the pump flow with the cardiac demand without causing hemodynamic instabilities. Crown Copyright (C) 2017 Published by Elsevier Ltd. All rights reserved.

Rotary blood pumps may be used as ventricular assist devices (VADs) to support patients with end-stage heart failure-‘rotary VADs’. Clinically, rotary VADs are operated at a constant speed which is set manually. Due to inadequate haemodynamic monitoring equipment outside of the hospital setting, device speed remains the same for weeks or months at a time, leaving clinicians in the dark, and patients vulnerable to harmful over- or under-pumping events. Therefore, it would be beneficial to have an implantable sensor which can measure blood pressure at the rotary VAD inlet or outlet and detect the onset of adverse events. In this study, a temperature compensated fibre Bragg grating (FBG) based strain sensor which can be incorporated into a VAD and used for continuous, real-time blood pressure monitoring is investigated. Error in the pressure reading between the developed and reference sensor occurred due to changes in temperature. A generalised linear model was used to compensate for temperature related error between 35-39º. Without temperature compensation, the mean error in the pressure reading over the desired range of -25 to 150 mmHg was approximately ±5 mmHg. The temperature compensated mean error over the same range was less than ±2 mmHg. The compensation technique was effective over a wide range of temperatures and pressures, demonstrating the potential of the sensor for continuous real-time blood pressure monitoring.

Rotary ventricular assist devices (VADs) are used to provide mechanical circulatory support. However, their lack of preload sensitivity in constant speed control mode (CSC) may result in ventricular suction or venous congestion. This is particularly true of biventricular support, where the native flow-balancing Starling response of both ventricles is diminished. It is possible to model the Starling response of the ventricles using cardiac output and venous return curves. With this model, we can create a Starling-like physiological controller (SLC) for VADs which can automatically balance cardiac output in the presence of perturbations to the circulation. The comparison between CSC and SLC of dual HeartWare HVADs using a mock circulation loop to simulate biventricular heart failure has been reported. Four changes in cardiovascular state were simulated to test the controller, including a 700 mL reduction in circulating fluid volume, a total loss of left and right ventricular contractility, reduction in systemic vascular resistance ( SVR) from 1300 to 600 dyne  s/cm5, and an elevation in pulmonary vascular resistance ( PVR) from 100 to 300 dyne  s/cm5. SLC maintained the left and right ventricular volumes between 69-214 mL and 29-182 mL, respectively, for all tests, preventing ventricular suction (ventricular volume = 0 mL) and venous congestion (atrial pressures > 20 mm Hg). Cardiac output was maintained at sufficient levels by the SLC, with systemic and pulmonary flow rates maintained above 3.14 L/min for all tests. With the CSC, left ventricular suction occurred during reductions in SVR, elevations in PVR, and reduction in circulating fluid simulations. These results demonstrate a need for a physiological control system and provide adequate in vitro validation of the immediate response of a SLC for biventricular support.

Due to a shortage of donor hearts, rotary left ventricular assist devices (LVADs) are used to provide mechanical circulatory support. To address the preload insensitivity of the constant speed controller (CSC) used in conventional LVADs, we developed a preload-based Starling-like controller (SLC). The SLC emulates the Starling law of the heart to maintain mean pump flow ([Formula: see text]) with respect to mean left ventricular end diastolic pressure (PLVEDm) as the feedback signal. The SLC and CSC were compared using a mock circulation loop to assess their capacity to increase cardiac output during mild exercise while avoiding ventricular suction (marked by a negative PLVEDm) and maintaining circulatory stability during blood loss and severe reductions in left ventricular contractility (LVC). The root mean squared hemodynamic deviation (RMSHD) metric was used to assess the clinical acceptability of each controller based on pre-defined hemodynamic limits. We also compared the in-silico results from our previously published paper with our in-vitro outcomes. In the exercise simulation, the SLC increased [Formula: see text] by 37%, compared to only 17% with the CSC. During blood loss, the SLC maintained a better safety margin against left ventricular suction with PLVEDm of 2.7 mmHg compared to -0.1 mmHg for CSC. A transition to reduced LVC resulted in decreased mean arterial pressure (MAP) and [Formula: see text] with CSC, whilst the SLC maintained MAP and [Formula: see text]. The results were associated with a much lower RMSHD value with SLC (70.3%) compared to CSC (225.5%), demonstrating improved capacity of the SLC to compensate for the varying cardiac demand during profound circulatory changes. In-vitro and in-silico results demonstrated similar trends to the simulated changes in patient state however the magnitude of hemodynamic changes were different, thus justifying the progression to in-vitro evaluation.

Control for dual rotary left ventricular assist devices (LVADs) used as a biventricular assist device (BiVAD) is challenging. If the control system fails, flow imbalance between the systemic and the pulmonary circulations would result, subsequently leading to ventricular suction or pulmonary congestion. With the expectation that advanced control approaches such as model predictive control could address the challenges naturally and effectively, we developed a synergistic first principles model predictive controller (MPC) for the BiVAD. The internal model of the MPC is a simplified state-space model that has been developed and validated in a previous study. A single Frank-Starling (FS) control curve was used to define the target pump flow corresponding to the preload on each side of the heart. The MPC was evaluated in a validated numerical model using three clinical scenarios: blood loss, myocardial recovery, and exercise. Simulation results showed that the MPC was effective in adapting to changes in physiological states without causing ventricular suction or pulmonary congestion. The use of MPC for a BiVAD eliminates the need for two controllers of dual LVADs thus making the task of controller tuning easier.

Preventing ventricular suction and venous congestion through balancing flow rates and circulatory volumes with dual rotary ventricular assist devices (VADs) configured for biventricular support is clinically challenging due to their low preload and high afterload sensitivities relative to the natural heart. This study presents the in vivo evaluation of several physiological control systems, which aim to prevent ventricular suction and venous congestion. The control systems included a sensor-based, master/slave (MS) controller that altered left and right VAD speed based on pressure and flow; a sensor-less compliant inflow cannula (IC), which altered inlet resistance and, therefore, pump flow based on preload; a sensor-less compliant outflow cannula (OC) on the right VAD, which altered outlet resistance and thus pump flow based on afterload; and a combined controller, which incorporated the MS controller, compliant IC, and compliant OC. Each control system was evaluated in vivo under step increases in systemic (SVR ∼1400-2400 dyne/s/cm(5) ) and pulmonary (PVR ∼200-1000 dyne/s/cm(5) ) vascular resistances in four sheep supported by dual rotary VADs in a biventricular assist configuration. Constant speed support was also evaluated for comparison and resulted in suction events during all resistance increases and pulmonary congestion during SVR increases. The MS controller reduced suction events and prevented congestion through an initial sharp reduction in pump flow followed by a gradual return to baseline (5.0 L/min). The compliant IC prevented suction events; however, reduced pump flows and pulmonary congestion were noted during the SVR increase. The compliant OC maintained pump flow close to baseline (5.0 L/min) and prevented suction and congestion during PVR increases. The combined controller responded similarly to the MS controller to prevent suction and congestion events in all cases while providing a backup system in the event of single controller failure.

BACKGROUND: Donation after circulatory death (DCD) represents a potential new source of hearts to increase the donor pool. We showed previously that DCD hearts in Greyhound dogs could be resuscitated and preserved by continuous cold crystalloid perfusion but not by cold static storage and could demonstrate excellent contractile and metabolic function on an in vitro system. In the current study, we demonstrate that resuscitated DCD hearts are transplantable.METHODS: Donor Greyhound dogs (n = 12) were divided into perfusion (n = 8) and cold static storage (n = 4) groups. General anesthesia was induced and ventilation ceased for 30 minutes to achieve circulatory death. Donor cardiectomy was performed, and for 4 hours the heart was preserved by controlled reperfusion, followed by continuous cold perfusion with an oxygenated crystalloid perfusate or by static cold storage, after which orthotopic heart transplantation was performed. Recovery was assessed over 4 hours by hemodynamic monitoring.RESULTS: During cold perfusion, hearts showed continuous oxygen consumption and low lactate levels, indicating aerobic metabolism. The 8 dogs in the perfusion group were weaned off bypass, and 4 hours after bypass produced cardiac output of 4.73 +/- 0.51 liters/min, left ventricular power of 7.63 +/- 1.32 J/s, right ventricular power of 1.40 +/- 0.43 J/s, and left ventricular fractional area shortening of 39.1% +/- 5.2%, all comparable to pre-transplant values. In the cold storage group, 3 of 4 animals could not be weaned from cardiopulmonary bypass, and the fourth exhibited low-level function.CONCLUSIONS: Cold crystalloid perfusion, but not cold static storage, can resuscitate and preserve the DCD donor heart in a canine model of heart transplantation, thus rendering it transplantable. Controlled reperfusion and cold crystalloid perfusion have potential for clinical application in DCD transplantation. (C) 2016 Published by Elsevier Inc. on behalf of International Society for Heart and Lung Transplantation. All rights reserved.

In this study, we evaluate a preload-based Starling-like controller for implantable rotary blood pumps (IRBPs) using left ventricular end-diastolic pressure (PLVED) as the feedback variable. Simulations are conducted using a validated mathematical model. The controller emulates the response of the natural left ventricle (LV) to changes in PLVED. We report the performance of the preload-based Starling-like controller in comparison with our recently designed pulsatility controller and constant speed operation. In handling the transition from a baseline state to test states, which include vigorous exercise, blood loss and a major reduction in the LV contractility (LVC), the preload controller outperformed pulsatility control and constant speed operation in all three test scenarios. In exercise, preload-control achieved an increase of 54% in mean pump flow ([Formula: see text]) with minimum loading on the LV, while pulsatility control achieved only a 5% increase in flow and a decrease in mean pump speed. In a hemorrhage scenario, the preload control maintained the greatest safety margin against LV suction. PLVED for the preload controller was 4.9 mmHg, compared with 0.4 mmHg for the pulsatility controller and 0.2 mmHg for the constant speed mode. This was associated with an adequate mean arterial pressure (MAP) of 84 mmHg. In transition to low LVC, [Formula: see text] for preload control remained constant at 5.22 L/min with a PLVED of 8.0 mmHg. With regards to pulsatility control, [Formula: see text] fell to the nonviable level of 2.4 L/min with an associated PLVED of 16 mmHg and a MAP of 55 mmHg. Consequently, pulsatility control was deemed inferior to constant speed mode with a PLVED of 11 mmHg and a [Formula: see text] of 5.13 L/min in low LVC scenario. We conclude that pulsatility control imposes a danger to the patient in the severely reduced LVC scenario, which can be overcome by using a preload-based Starling-like control approach.

INTRODUCTION:Left ventricular assist devices are crucial in rehabilitation of patients with end-stage heart failure. Whether cardiopulmonary function is enhanced with higher pump output is unknown.METHODS:10 patients (aged 39±16 years, mean±SD) underwent monitored adjustment of pump speed to determine minimum safe low speed and maximum safe high speed at rest. Patients were then randomized to these speed settings and underwent three 6-minute walk tests (6MWT) and symptom-limited cardiopulmonary stress tests (CPX) on separate days.RESULTS:Pump speed settings (low, normal and high) resulted in significantly different resting pump flows of 4.43±0.6, 5.03±0.94, and 5.72±1.2 l/min (P<.001). There was a significant enhancement of pump flows (greater at higher speed settings) with exercise (P<0.05). Increased pump speed was associated with a trend to increased 6MWT distance (P=.10); and CPX exercise time (p=.27). Maximum workload achieved and peak oxygen consumption were significantly different comparing low to high pump speed settings only (P<.05). N-terminal-pro-B-type natriuretic peptide release was significantly reduced at higher pump speed with exercise (P<.01).CONCLUSIONS:We have found that alteration of pump speed setting resulted in significant variation in estimated pump flow. The high-speed setting was associated with lower natriuretic hormone release consistent with lower myocardial wall stress. This did not, however, improve exercise tolerance.

As a left ventricular assist device is designed to pump against the systemic vascular resistance (SVR), pulmonary congestion may occur when using such device for right ventricular support. The present study evaluates the efficacy of using a fixed right outflow banding in patients receiving biventricular assist device support under various circulatory conditions, including variations in the SVR, pulmonary vascular resistance (PVR), total blood volume (BV), as well as ventricular contractility. Effect of speed variation on the hemodynamics was also evaluated at varying degrees of PVR. Pulmonary congestion was observed at high SVR and BV. A reduction in right ventricular assist device (RVAD) speed was required to restore pulmonary pressures. Meanwhile, at a high PVR, the risk of ventricular suction was prevalent during systemic hypotension due to low SVR and BV. This could be compensated by increasing RVAD speed. Isolated right heart recovery may aggravate pulmonary congestion, as the failing left ventricle cannot accommodate the resultant increase in the right-sided flow. Compared to partial assistance, the sensitivity of the hemodynamics to changes in VAD speed increased during full assistance. In conclusion, our results demonstrated that the introduction of a banding graft with a 5 mm diameter guaranteed sufficient reserve of the pump speed spectrum for the regulation of acceptable hemodynamics over different clinical scenarios, except under critical conditions where drug administration or volume management is required.

This study in five large greyhound dogs implanted with a VentrAssist left ventricular assist device focused on identification of the precise site and physiological changes induced by or underlying the complication of left ventricular suction. Pressure sensors were placed in left and right atria, proximal and distal left ventricle, and proximal aorta while dual perivascular and tubing ultrasonic flow meters measured blood flow in the aortic root and pump outlet cannula. When suction occurred, end-systolic pressure gradients between proximal and distal regions of the left ventricle on the order of 40-160 mm Hg indicated an occlusive process of variable intensity in the distal ventricle. A variable negative flow difference between end systole and end diastole (0.5-3.4 L/min) was observed. This was presumably mediated by variable apposition of the free and septal walls of the ventricle at the pump inlet cannula orifice which lasted approximately 100 ms. This apposition, by inducing an end-systolic flow deficit, terminated the suction process by relieving the imbalance between pump requirement and delivery from the right ventricle. Immediately preceding this event, however, unnaturally low end-systolic pressures occurred in the left atrium and proximal left ventricle which in four dogs lasted for 80-120 ms. In one dog, however, this collapse progressed to a new level and remained at approximately -5 mm Hg across four heart beats at which point suction was relieved by manual reduction in pump speed. Because these pressures were associated with a pulmonary capillary wedge pressure of -5 mm Hg as well, they indicate total collapse of the entire pulmonary venous system, left atrium, and left ventricle which persisted until pump flow requirement was relieved by reducing pump speed. We suggest that this collapse caused the whole vascular region from pulmonary capillaries to distal left ventricle to behave as a Starling resistance which further reduced right ventricular output thus contributing to a major reduction in pump flow. We contend that similar complications of manual speed control also occur in the human subject and remain a major unsolved problem in the clinical management of patients implanted with rotary blood pumps.