Ji-Feng Chen

Adaptation of Tissue to a Chronic Heat Load

Determination of the chronic effect of heat on tissue is one of the important issues facing mechanically actuated total artificial heart (TAH) development. In an effort to characterize this effect, implantations of heating devices producing constant heat fluxes of 0.04 watts/cm2, 0.06 W/cm2, and 0.08 W/cm2 were performed in 11 calves (H-series). Heated disks were implanted adjacent to lung and muscle tissue for a period of 7 weeks. Temperature sensors were placed at the surface as part of the heater assemblies. The results showed that initially, temperature elevations above body temperature (delta T) were 6.4 +/- 0.6 degrees C, 4.5 +/- 0.2 degrees C, and 1.8 +/- 0.5 degrees C at the muscle heater surface for 0.08, 0.06, and 0.04 W/cm2, respectively. At 2 weeks after implant delta T values changed to 5.5 +/- 0.6 degrees C, 3.4 +/- 0.2 degrees C, and 1.8 +/- 0.2 degrees C, respectively. Seven weeks after implant, delta T values decreased to 3.7 +/- 1.2 degrees C, 2.8 +/- 0.1 degrees C, and 0.8 degrees C for 0.08, 0.06, and 0.04 W/cm2, respectively. The authors think this change is attributable to an adaptive response of the tissue to increase heat dissipation through angiogenesis. Results from three TAH cases indicated that at two measured tissue interfaces, delta T decreased by 1 degrees C during a 15 day period. At the same time, the waste heat (volts x current in-flow x afterload to the blood) remained constant at 11.1 +/- 0.5 W during this period. This decrease in delta T corresponded to that observed for the H-series experiments at the higher heat fluxes. Thus, it appears that adaptation observed in the H-series experiments also is seen for tissues surrounding heat sources such as the TAH.

Continuing development of the Cleveland clinic-nimbus total artificial heart

A completely implanted total artificial heart (TAH) is under development by Nimbus, Inc., and the Cleveland Clinic Foundation (CCF). Key features of the system include an electrohydraulic energy converter, an automatic control system that produces a Frank-Starling response, and dual ventricles composed of graphite-epoxy and titanium with gelatin blood contacting surfaces. The system is controlled by a single substrate, hybridized microcircuit (the hybrid). Fabrication of the TAH control hybrid has recently been completed and testing begun. Its design emphasizes simplicity, reliability, and efficiency. Particular attention was given to optimizing thermal management. Externally controlled TAH systems have been used in eight in vivo experiments of up to 120 days duration. In the last two of these experiments, a variable volume device was also implanted with excellent results. In vivo use of the system has demonstrated the Frank-Starling pump response, but the systems quickly reach maximum output with the bovine animal models. Human fitting studies, including adult patients undergoing heart transplantation, demonstrated satisfactory fit of the pump within the pericardium without compression of the vascular structures or chest wall. Measurements of chest circumference, plain chest films, and transesophageal echocardiograms should provide reliable predictions of pump fit in the majority of patients.

The Cleveland Clinic-Nimbus total artificial heart: Design and in vitro function

We describe the design and in vitro testing of the Cleveland Clinic-Nimbus electrohydraulic permanent total artificial heart as it nears completion of development. The total artificial heart uses an electric motor and hydraulic actuator to drive two diaphragm-type blood pumps. The interventricular space contains the pump control electronics and is vented to an air-filled compliance chamber. Pericardial tissue valves and biolized blood-contacting surfaces potentially eliminate the need for anticoagulation. In vitro studies on a mock circulatory circuit demonstrated preload-sensitive control of pump output over the operating range of the blood pump: 70 to 160 beats/min and 5 to 9.6 L/min at right and left atrial pressures of 1.0 to 7.0 mm Hg and 5.0 to 12.0 mm Hg, respectively. The pump output was found to be insensitive to afterload over a range of 15 to 40 mm Hg mean pulmonary artery pressure and 60 to 130 mm Hg mean systemic pressure. The left master alternate control mode balanced the ventricular outputs during simulated bronchial artery shunting of up to 20% of cardiac output. A 10% to 15% right-pump, stroke-volume limiter balanced ventricular outputs during maximum output of 9.6 L/min. In response to a sustained increase in systemic venous return, the pump increased output by 2 L/min (29%) in 35 seconds. Thus the Cleveland Clinic-Nimbus total artificial heart meets the National Heart, Lung, and Blood Institute hemodynamic performance goals for devices being developed for permanent heart replacement. The biolized blood-contacting surfaces should decrease the risk of thromboembolism associated with circulatory assist devices.

Progress in Cleveland Clinic-Nimbus total artificial heart development

A totally implantable, Cleveland Clinic-Nimbus total artificial heart (TAH) uses electrohydraulic energy conversion and an automatic left master-alternate mode control scheme, with a filling sensitivity of 1.0 l/min/mmHg and a maximum output of 9.5 l/min. The TAHs were tested in 12 calves for 1-120 days with normal major organ and blood cell function. Post-operative suppression of platelet aggregation recovered by the second post-operative week. The gelatin-coated pump surface generally was clean without any anticoagulants and free from infection. Embolism, which occurred in two cases, was caused by complications attributable to fungal infection in a Dacron graft and by thrombus formed around a jugular vein catheter. A system with a hybridized microcircuit controller in the interventricular space has been tested successfully in the three most recent cases, with a peak device surface temperature elevation of 6.5 degrees C. Heat effects were confined to the tissues immediately adjacent to the hottest spots. The carbon fiber-reinforced epoxy housing and 60 ml butyl rubber compliance chamber showed good tissue compatibility with a thin, fibrous tissue capsule. The transcutaneous energy transmission system and the internal battery functioned well as designed in the most recent animal implant.

Muscle powered circulatory assist device for diastolic counterpulsator.

A diastolic counterpulsator that uses either skeletal muscle or pneumatic actuation was developed. The unit is positioned between the latissimus dorsi and the chest wall, without interference with collateral blood supply, and is connected in series with the descending aorta. The system was able to generate stroke volumes between 52 and 16 ccs against pressures of 60 and 140 mmHg, respectively. Stroke work at 200 msec stimulation averaged 2.8 X 10(6) ergs. Power output at an afterload of 100 mmHg, and at a rate of 60 bpm, was 0.51 W. Back-up pneumatic actuation provided by an intraaortic balloon pump resulted in a 46% increase in the endocardial viability ratio (EVR).

Effects of mechanical ventilation and spontaneous respiration on hemodynamics in calves with total artificial hearts

The effects of respiration on hemodynamics were evaluated in four Holstein calves with total artificial hearts (TAH). The electrohydraulic actuated E4T-TAH has a continuously reciprocating actuator packaged between two alternately ejecting blood pumps that passively fill. The hemodynamic parameters (right atrial pressure [RAP], left atrial pressure [LAP], pulmonary artery pressure [PAP], aortic pressure [AoP]), and right and left pump filling (Rt% fill and Lt% fill) were measured when the animal was intubated and mechanically ventilated. These measurements were repeated with spontaneous respiration after the animal was extubated. With mechanical ventilation, LAP, PAP, and AoP were significantly higher during inspiration than during expiration. However, RAP during inspiration was slightly lower than that during expiration. The Rt% fill during inspiration was significantly lower than during expiration, but Lt% fill during inspiration was significantly higher than during expiration. During spontaneous respiration, these changes were opposite to those observed during mechanical ventilation. That mechanical ventilation generates positive intrathoracic pressure during inspiration, but spontaneous respiration generates negative pressure may explain these results. The change in venous return to the right atrium caused the change in RAP to be opposite in direction to that of the other pressures.

Initial In Vivo Evaluation of the DexAide Right Ventricular Assist Device

Despite the increasing use of left ventricular assist devices for patients with end-stage congestive heart failure, no implantable, centrifugal right ventricular assist devices (RVADs) are available for those patients with significant right ventricular failure. The DexAide RVAD was developed to provide an implantable RVAD option to surgeons. The aim of this study was to evaluate pump performance in an acute in vivo model. The DexAide RVAD, developed as a modified CorAide left ventricular assist device, was implanted between the right ventricle and the pulmonary artery in four healthy calves. Pump speed was varied from 1800 rpm to 3600 rpm. RVAD performance was analyzed acutely at baseline and under conditions of low circulating volume, high contractility, high pulmonary arterial pressure, vasodilation, and low contractility. Pump flow was well maintained even under conditions of high pulmonary arterial pressure and vasodilation, with the exception of low circulating volume. Under all conditions, pulmonary arterial pressures were not affected by changing pump speed. The DexAide RVAD demonstrated acceptable hemodynamic characteristics for use as an implantable RVAD in the initial acute studies. Further studies are ongoing to examine the biocompatibility of the pump under chronic conditions.

Development of an Implantable Total Artificial Heart: Initial Animal Experiments

After 35 years of research and development, the artificial heart program at the Cleveland Clinic is approaching one of its goals; development of a totally implantable total artificial heart. This total artificial heart, actuated by an electrohydraulic energy converter developed by Nimbus, has been tested in seven calves for up to 45 days. A left master mode of operational control has proven workable, maintaining both right and left atrial pressures within the physiological ranges. A maximum in vivo output of 8.7 ± 0.81/min was obtained with a left side pump sensitivity of approximately 1.01/min-mmHg filling pressure. These data indicate that our system meets the design goal specified by the National Heart, Lung, and Blood Institute (NHLBI). Details of animal experiments currently underway are described.

Hemodynamic changes with posture in calves with total artificial heart

Hemodynamic changes with posture, sitting versus standing, were analyzed in five Holstein calves with the Cleveland Clinic-Nimbus TAH. This total artificial heart (TAH) has a left master alternate control mode that adjusts the pump rate and consequently pump flow proportional to the pulmonary venous return to the left pump (AUTO period). However, in this series of experiments, the pump reached its maximum beat rate within 1-5 days post operatively, after which pump flow could not increase (MAX period). Hemodynamic parameters (RAP, LAP, PAP, AoP, and pump flow) were obtained every 15-20 min throughout the experiments for as long as 120 days and averaged for each posture for each period. During the AUTO period, the flow while standing was significantly higher than that while sitting (standing: 8.7 +/- 0.2 L/min; sitting: 7.5 +/- 0.4 L/min; p < 0.05), and the systemic vascular resistance (SVR) was significantly lower (standing: 895 +/- 93 dyne.sec.m-5; sitting: 1,041 +/- 124 dyne.sec.m-5; p < 0.05). During the MAX period, the AoP and SVR standing were significantly lower than those sitting (AoP standing: 91 +/- 7 mmHg; AoP sitting: 98 +/- 7 mmHg; p < 0.05; SVR standing: 652 +/- 75 mmHg; SVR sitting: 730 +/- 96 mmHg; p < 0.05). The Cleveland Clinic-Nimbus TAH responded well to these changes in position, increasing pump flow and maintaining the AoP during the AUTO period.

New crisscross-shaped port design for universal serial pumps

The long range goal is the development of a clinically useful, implantable, skeletal muscle powered cardiac assist device (MCAD). To accomplish this goal, two criteria must be met: good anatomic fit, and antithrombogenicity. Because of the relative locations of the latissimus dorsi (LD) muscle and aorta, there are two possible port arrangements: crisscrossed (C design), in which the ports are crossed to anastomotic sites, and prong shaped (P design), in which no crossover takes place. The purpose of this paper is to determine which of these designs is best from a fluid dynamic perspective, and hence has the best possibility for low thrombogenicity. Flow visualization (FV) techniques were used during two pumping conditions in a mock loop: worst case (MCAD off) and best case (MCAD driven optimally). Results of the MCAD off tests showed that both designs required immediate actuation (for example, an IABP console). However, FV studies under optimal conditions indicated superiority of the C design, most likely due to kinetic energy-induced rotary motion combined with a minimal interport distance. It is concluded that the C design provides ideal flow dynamics, even in valveless pumps, and also has application to valved devices.