Kiraly R

Mechanical properties of aortas and pulmonary arteries of calves implanted with cardiac prostheses

Abstract Left ventricular assist devices (LVAD) were implanted in calves of 3-months old between the natural left ventricular apices and middle descending aortas, while total artificial hearts (TAH) were implanted to replace the natural heart ventricles. The stiffness and strength of upper and lower descending aortas obtained from the calves implanted with the LVADs for 1–2 months were significantly lower than those of non-pumped control calves, accompanied by local detachment and damage of endothelial surfaces, while the mechanical properties of the aortas from TAH-implanted calves were very similar to those of the control calves. However, the decreased stiffness and strength of the aortas in the LVAD-implanted calves were recovered to the control levels by pumping for another 1 month or by the pump removal. These characteristic changes in aortic mechanics and structures by the LVAD pumping for an intermediary duration were ascribed to the distortion of blood flow produced around the anastomosis of the pump outflow conduit to the descending aorta.

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.

145 days survival of calf with total artificial heart (TAH).

A calf with a biolized TAH was maintained in reasonably good physiological condition for a major portion of a 145-day experiment as indicated by near normal growth rate and laboratory data. The mechanism for the high CVP and CBV at the beginning and end of the experiment were correlated with protein metabolism. No evidence of thromboembolism was found at autopsy and only modest congestion with minimal parenchymal damage was observed. The cardiac prosthesis itself was free of thrombus, although slight calcification was found on the valves and diaphragms. The pump performance, however, remained satisfactory. In addition, endothelialization appeared to be starting on a portion on the inside of the pump.

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.

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.

Heat Dissipation through the Blood Contacting Surface of a Thermally Driven LVAS

A heat exchanger for a totally implantable heat driven LVAD is an essential element in overall system thermal management. The heat exchange is accomplished by supplying cooling water from a pusher-plate driven water pump to the engine and then to the heat exchanger on the pump housing. The temperature of the interface between the blood and pump surface is of critical importance for clinically acceptable operation of the system. Temperatures were measured by instrumenting a pump housing with thermocouples and an electric heater on a mock circulatory loop. Flows were varied from 1 to 8 l/min and heat input was 20 watts. At 1.0 l/min pump flow the maximum inner surface temperature rise is 4.5°C. In vitro tests were conducted to examine the effect of elevated temperature on platelete function. Both platelet aggregation and adhesion were reduced at elevated temperatures of 42 and 478C indicating a potential benefit of reduced thrombogenesis on the heated housing surface.

Anatomic fitting studies of a total artificial heart in heart transplant recipients. Critical dimensions and prediction of fit.

Anatomic fitting studies of the Cleveland Clinic-Nimbus total artificial heart were performed in 33 patients undergoing heart transplantation. The pump fit in the pericardial space in 20 men (80%) and 4 women (50%). There was no significant difference between the Fit and Non-Fit groups in external chest dimensions. Among 42 intrathoracic dimensions, the distance from the center of the mitral valve to the diaphragm (Fit: 5.6 +/- 2.2 cm, Non-Fit: 3.6 +/- 0.4 cm, p < 0.00001) and the distance from the caudal end of the pulmonary valve to the diaphragm (Fit: 9.4 +/- 1.6 cm, Non-Fit: 6.3 +/- 0.8 cm, p < 0.0001) were the most critical. To predict anatomic fit, an index (A x B x C) was obtained from chest X-ray measurements (A, the craniocaudal distance from the dorsal region of the 8th left rib to the left diaphragm; B, the maximum left chest width; and C, the maximum anteroposterior sternum-vertebrae dimension). The pump fit in 88.5% of the patients with an index above 1200 cm3, whereas it fit in only 14.3% of the patients with an index below 1200 cm3 (p < 0.001). This index was an easily obtainable, good predictor of anatomic fit.

Initial in vivo tests of an electrohydraulic actuated total artificial heart

The authors are involved in developing a total artificial heart (TAH) for permanent human use. This device was designed to fit human anatomy, and it has housings made of carbon fiber-epoxy composite and titanium. Tissue valves and protein coating of blood contacting surfaces minimize the need for anticoagulants. A continuously reciprocating electrohydraulic actuator is packaged between two alternately ejecting and passively filling ventricles. The control system varies the pump rate to maintain average left ventricular filling at 90%. This TAH in vivo successively progressed through 1, 5, 9, and 45 day implants in calves of 84, 94, 82, and 82 kg preoperative body weights. The operating modes include automatic and fixed rate. The chronic and acute effects of varying the right pump displaced stroke volume indicated the need for it to be limited to 85% of that of the left for stable hemodynamics at maximum flow. The pump exhibited afterload insensitive and preload sensitive performance. Pump output ranged from 4.0-9.5 L/min at left atrial pressures of 7-16 mmHg at pump rates of 80-160 beats/min in these four experiments. These data suggest that this device will meet clinical hemodynamic requirements; it has the potential for total implantable cardiac replacement.

Surface characteristics of cardiac prostheses in vivo

The pseudoneointima (PNI) deposited onto a cardiac prosthesis surface reflects many factors of biocompatibility, surface morphology, flow distribution, design, animals physiological condition, and duration. In the evaluation of any prosthesis, the PNI is one of the prime considerations from both material and functional standpoints. Historically, Dacron fabric has been used as an internal lining for cardiac prostheses. However, we have observed cracks on the Dacron fibers, fiber fracture, fiber protrusion, and poor attachment to the diaphragm, which can cause potentially disastrous complications. In addition, there are basic differences in the PNI formation on aldehyde-treated pericardium and natural aortic valves as compared to the Dacron fabric. 1) Minimal degeneration takes place on the chemically treated natural tissue compared with the fabtic surface. Intact cells on the tissue suggest a greater compatibility. In later specimens (13 and 24 days), there is active cell infiltration onto the pericardium structure with capillary formation. 2) The deposits on natural tissue are mostly fibrin, with minimum cellular involvement and a trend toward reduction in thickness. 3) Fibroblast cells are found on the natural tissue as early as 7 days but were not observed on the Dacron fabrics. Based on these findings, the Dacron fabric-covered diaphragm studied was not favorable for use in long-term implantation of cardiac prostheses.

In vitro evaluation of automatic control performance of a total artificial heart with changes in pump orientation

Unlike in animal experiments, the pump orientation of a total artificial heart (TAH) can change remarkably in humans with the recipients posture (upright, supine, or prone), thus affecting its filling characteristics. The left master alternate control mode of the Cleveland Clinic-Nimbus (CC-N) TAH adjusts beat rate by maintaining the left pump at 90% filling, producing a Frank-Starling like preload sensitivity. In order to verify that the CC-N TAH functions properly regardless of the gravity effects on pump filling, the preload sensitivity curves of the CC-N TAH were evaluated on a mock circulatory loop with the simulated supine (right pump up) and prone (left pump up) positions in humans. The right preload sensitivity was slightly higher when the right pump was up versus down, and likewise the left preload sensitivity was higher when the left pump was up versus down. Despite these gravity effects on pump filling, right and left preload sensitivity remained within physiologic range and the automatic control of the CC-N TAH functioned properly without significant postural effects.