Animal implantation results with the Utah-100 total artificial heart.

The Utah-100 total artificial heart was designed to have increased reliability over the Jarvik-7 total artificial heart, achieve better fit, and minimize device associated thrombus formation, without decreasing the function. The Utah-100 heart was tested in 28 calves and 3 sheep. The smallest animal at the time of implantation weighted 54 kg. Mean survival duration was 78 days (range, 1-331 days), with 14 animals surviving longer than 60 days. Multiple organ function was maintained satisfactorily with the Utah-100 artificial heart, and mean plasma free hemoglobin values in the calves that survived longer than 100 days were less than 10 mg/dl. Hemorrhage was the main cause of death in animals dying within 30 days after implantation (5/13, 38%); infection was another primary cause of death or termination (4/31, 13%). Deaths due to mechanical failure occurred from valve or diaphragm failure in two cases, yielding a 91% reliability at a 90% confidence level for 60 days' support. No animal died because of driver or other technical failure. Utah-100 hearts showed superior antithrombogenicity in the connector and valve-related areas when compared with the results of the Jarvik-7 heart, which was also fabricated and implanted in our laboratory (p less than 0.01). With these test results, the authors anticipate that the Utah-100 heart will be a safe and effective device for interim use as a bridge to heart transplantation.

Electrohydraulic ventricular assist device development.

An electrohydraulic ventricular assist device has been developed. An axial flow pump driven by a brushless DC motor provides actuation. Energy is supplied by internal Ni/Cd batteries and by external Ag/Zn batteries, both rechargeable. Electromagnetic induction is used to pass energy through the skin with a transcutaneous energy transfer (TET) system. Physiologic control, battery management, motor commutation, and communication functions are performed by a surface mount internal controller. An infrared data link within the TET coils provides bidirectional communication between the external and internal controllers. A computer model was developed to predict system performance. The dimensions are 180 mm x 116 mm x 40 mm. An in vitro system pumped 5.7 L/min at 10 mmHg inflow and 100 mmHg outflow pressure. The internal battery can provide the projected energy requirements for 40 min after 540 charge/discharge cycles, and the external battery is capable of 4 hr of operation after 150 cycles. The TET system can deliver 60 W of power and exceeds 80% efficiency between 15 and 30 W. The device configuration is based on human cadaver and intraoperative fit trials. The device is being modified for calf implantation by redirecting the blood ports, increasing the output, and incorporating the internal controller in the unified device base.

A blood pump with an interatrial shunt for use as an electrohydraulic total artificial heart.

A recently designed blood pump subsystem for the completely implantable electrohydraulic total artificial heart (EHTAH) has been developed and is under evaluation. The subsystem consists of joined left and right ventricles, atrial cuffs with an interatrial shunt (IAS), and two outflow grafts. The ventricles were developed to fit within the pericardial space based on the results of anatomic fit trials. An optimized configuration for animal use, which was adaptable for human use with minimal modification, was identified. The core dimensions of the ventricles with an energy converter are approximately 10 x 11 x 7 cm. Maximum output and stroke volume are 9.2 L/min and 81 ml, respectively. The IAS is used to balance the volumetrically coupled EHTAH, and is made by forming an orifice in the common septum of the left and right atrial cuffs. Performance and durability of the IAS were examined in animal experiments for up to 9 days. The diameter of the IAS was 3.4-5.5 mm, and the left-right atrial pressure difference ranged from 2 to 10 mmHg, with 0.57-1.48 L/min of theoretically calculated shunt flow. No evidence of thrombus formation was found in or around the IAS at autopsy. The entire EHTAH system with a new blood pump is being assembled for long-term animal studies.

Effects of surface integrity on the fatigue life of thin flexing membranes.

It has been known for some time that surface integrity has an effect on the fatigue life of metals and "brittle" polymers. In cardiovascular applications of polymeric materials, emphasis is placed on elastomers having extended flexure lifetimes (i.e., fatigue life). The effect of surface integrity on the performance properties of Biomer (Ethicon, Inc, Somerville, NJ) a segmented polyurethane used in many blood contacting devices, is being investigated using uniaxial tensile tests in air at room temperature, and biaxial fatigue tests in deionized water at body temperature. Tensile tests were done using ASTM-D-882: Standard Test Methods for Tensile Properties of Thin Plastic Sheeting. No significant differences were noted in the stress-strain curves for specimens with various surface finishes. Fatigue tests were performed using an apparatus developed to allow for the exposure of thin-sheet polymer specimens to fluid at body temperature, while being biaxially strained. Because no standard test method was available, a test protocol was developed with reference to ASTM-D-671-78: Standard Test Methods for the Flexural Fatigue of Plastics by Constant Amplitude of Force. Stress versus life cycle data for specimens with differing surface finishes are being collected. Results to date suggest fatigue life of thin flexing membranes will decrease with increasing order of surface roughness, and fatigue properties are more sensitive to effects of changes in surface integrity than tensile properties measured by monotonic loading.

Development of a biocompatible hermetically sealed electrical feedthrough.

A new biocompatible hermetically sealed electric wire feedthrough has been developed for use in a totally implantable artificial heart (TAH) and ventricular assist device (VAD). This feedthrough allows electric current to pass through a rigid polyurethane (Isoplast 301, Dow Chemical U.S.A., Midland, MI) housing wall. The implantable housing is exposed externally to tissue and body fluids and is filled with low viscosity silicone oil (decamethyltetrasiloxane) which acts as a hydraulic fluid. The feedthrough prevents fluid transfer which caused early prototype devices to fail. The feedthrough consists of external and internal wires insulated with soft segmented polyurethane (Biomer, Ethicon, Somerville, NJ) and soldered to opposite ends of a conductive pin. The pin and the wire connections are encapsulated in Biomer, forming a leak-free barrier between the housing wall and the wire insulation. The pin soldered between the two wires prevents leakage from between the strands and the insulation.

Mechanical failures of the pneumatic Utah-100 and Jarvik total artificial hearts. A comparative study.

Jarvik-5 and Jarvik-7 total artificial hearts (TAHs) and Utah-100 TAHs were fabricated and implanted in calves and sheep. In the Jarvik series, 30.7% had mechanical failures (16.1% catastrophic). In the Utah-100 TAH series, 11.1% had mechanical failures (3.7% catastrophic). Failures were classified as: 1) diaphragm failures; 2) valve-holding ring failures; 3) air-leak failures; and 4) prosthetic valve failures. Marked reduction in mechanical failure for the Utah-100 TAH is attributed to progressive component redesign, material selection, and more stringent quality control criteria.

Preliminary in vitro evaluation of the first neonatal total artificial heart.

A neonatal total artificial heart (TAH), used as a bridging device, can offer circulatory support for patients suffering from otherwise insupportable and inoperable congenital cardiac defects. The choice of the 7.0 ml stroke volume (SV) was based on reported studies on cardiac output (CO) requirements and maximum dimensions of a neonate size TAH. This SV will allow a bridging period of up to 10 weeks in the growing neonate. For in vitro testing purposes, "high-profile" ball valves of in-house design (10-13 mm ID) were used. Redesign of the existing in vitro testing systems, including mock circulation and high-flow blood reservoirs, was required for the smaller device. Mock circulation studies (rates 90-160 BPM, full-fill and ejection modes) showed adequate device performance, with CO values well above the reported marginal output value of 139 ml/kg/min.

Design mediated thrombus reduction in the Utah-100 total artificial heart.

The Utah-100 total artificial heart was initially designed and tested in 1983. General design goals, including improved fit for human application, improved reliability, and elimination of thrombus formation, were identified as improvements over the clinically used Jarvik-7 artificial heart, previously developed at the Institute for Biomedical Engineering, University of Utah. Specific design goals included 1) elimination of connector and valve-associated thrombus formation and 2) elimination of gross mineralization, thrombus formation, and creases on the blood-pumping diaphragm of the device. Explant retrieval results from 29 calves and sheep implanted with the Jarvik-7 artificial heart were compared with results from 25 calves and sheep implanted with the Utah-100 artificial heart. Macroscopic thrombus formation was found in 44% of the connectors of the Jarvik-7 artificial-hearts, compared with 2% (p less than or equal to 0.01) in animals with the Utah-100 artificial heart. Subvalvular and supravalvular thrombi were observed in 33% of the valves in the Jarvik-7 artificial heart and 10% (p less than or equal to 0.01) of the valves in the Utah-100 artificial heart. Mineralization of the pumping diaphragm was observed in 12% of the animals implanted with the Jarvik-7 artificial heart and in 4% of the animals with the Utah-100 diaphragms. Thrombus formation in the diaphragm-housing interface occurred in 2% of Jarvik-7 ventricles and in 6% of the Utah-100 ventricles. There were no identifiable diaphragm creases in the Utah-100 diaphragms, but a 10% incidence was found in Jarvik-7 devices. These results validate substantial progress toward improved design and fabrication methods in the Utah-100 total artificial heart.

In vitro development of automatic control for the actively filled electrohydraulic heart.

The in vitro development of automatic control of the actively filled, alternately pumped, volumetrically coupled, electrohydraulic total artificial heart was the goal of this investigation. Control features under study were (a) cardiac output (CO) response to preload; (b) CO relationship to mean aortic pressure (AoP); and (c) control of balanced ventricular outputs. A modified pulmonic valve to increase backflow was used as a balancing mechanism. Hydraulic fluid pressure transducers monitored diastolic pressures, and microprocessor control of motor speed maintained in a mild suction to yield filling rate dependent on atrial pressure. Results indicated a rise in CO from 5 to 9 L/min, with a change in mean right atrial pressure (RAP) from 0 to 7 mm Hg. No significant difference in CO was found as AoP was varied from 80 to 120 mm Hg with a maximum variation of +/- 0.5 L/min on CO and +/- 1 mm Hg on RAP. Balance was maintained for bronchial flows up to 50% with mean left atrial pressure never exceeding 15 mm Hg. An alternately pumped electrohydraulic heart was automatically controlled to respond sensitively to preload changes. Afterload changes did not alter the CO response curve. Automatically controlled, balanced ventricular outputs were maintained.

Microbiologic survey of prosthetic blood pumps presterilization and poststerilization and at explant retrieval.

Device-associated infection remains a major complication of implanted total artificial hearts (TAH). The possibility of microbes being introduced on the device was investigated by conducting a gross microbial assay, pre- and poststerilization, and following explant retrieval. Culture samples were obtained from the housing, base, and blood-contacting diaphragm of Utah-100 artificial ventricles. Additional samples were obtained from atrial sewing cuffs, outflow grafts, drive lines, and percutaneous leads, along with reference control samples prior to ethylene oxide sterilization (ETO). Culturing was repeated poststerilization and at device explant retrieval. Positive bacterial and fungal cultures were found in 24% of the presterilization samples; in the poststerilization samples, positive cultures were found in 6%. Following device explant retrieval, 84% of the cultures were positive. The reference control samples were positive in a limited number of the poststerilization samples. There was no correspondence of the species of micro-organisms found at the same location for each sampling condition. These data demonstrate that the surfaces of the TAH can become contaminated during fabrication. The presence of microbial activity poststerilization raises the possibility of inadequacy of the ETO protocol used with these devices, or contamination of the surgical field. Hearts at explant retrieval had cultures positive for microbes differing from those identified prior to implantation. This finding suggests that device-associated micro-organism colonization occurs through a source other than manufacturing or surgical contamination.

Thrombus with infection in total artificial heart animals.

From January 1980 to December 1990, several types of total artificial hearts were implanted into 378 animals. In a retrospective study of these animals, 147 (39%) were found to have thrombus with infection (T&I). The criteria for diagnosis was thrombus formation in the artificial heart and a positive blood culture. The most common pathogen isolated from T&I animals was Pseudomonas species. Concurrent skin lesions and contamination from the pressure lines may be the primary sources of infection, but bacterial translocation from the intestine is another possible route. The main pathological findings at necropsies of artificial heart animals with T&I were associated with sepsis, congestive heart failure, infected thrombus, thromboembolism, and multiple organ infarctions. Most thrombi appeared to have originated from valve junctions and connectors. On the basis of these observations, a possible mechanism for pathogenesis of T&I has been proposed. The results suggest that design improvements and surface modifications to reduce thrombosis are important factors that should be carefully considered. Similarly, it is important to eliminate the route of entry of pathogenic microorganisms. These findings imply that bacterial interaction with thrombus, device related bacterial colonization, and host immunomodulation and gut barrier function following artificial heart implantation need further investigation.

Microbially infected thrombus in animals with total artificial hearts.

In a retrospective study of 330 animals with total artificial hearts (TAH), 103 (31%) had microbially infected thrombi (MIT). The incidence of MIT approximated 75% in the animals surviving more than 100 days. The most common pathogen isolated from animals with MIT was Pseudomonas. Most thrombi appeared to have originated from valve junctions and connectors. Methods to prevent MIT should be aimed at eliminating thrombus formation by improved design and materials and controlling the route of bacterial colonization. These findings suggest that bacterial interaction with the thrombus, device-related bacterial colonization, host immunomodulation, and gut barrier function after TAH implantation need further study.

A total artificial heart for neonates allowing bridging to transplantation.

Since the early 1980s, a rapid increase in successful pediatric heart transplantation has improved the chance of survival for many children suffering from otherwise fatal cardiomyopathies or congenital cardiac defects. During the last 5 years, heart transplantation in neonates and infants (0-28 days and 1-12 months, respectively) has been the most rapidly growing area within the pediatric patient population. No adequate mechanical circulatory support system, designed to be used as a bridge to transplantation, is available for many of these pediatric patients. Neonates are the smallest candidates to potentially benefit from heart transplantation, and their often acute need for either heart transplantation or temporary circulatory support indicates that any new development of a pediatric bridging device should focus on this youngest group. Subsequently, such a device may be modified to any weight or age group. An innovative total artificial heart design was developed in an attempt to meet the anatomic and physiologic requirements of neonates and infants. This report discusses the rapidly growing pediatric heart transplantation patient population, as well as an innovative total artificial heart design.

Comparative hematological data from animals implanted with a total artificial heart containing different valves.

A review of animals receiving a TAH with 4 mechanical valves suggests that the least damage to the blood cell components is associated with the BS valve when compared with the MH valve at similar heart rates. Clinical anemia in varying stages was observed in most animals in this study. However, most calves compensated for the increased rate of hemolysis and none required blood transfusions. The BS valve would appear to combine minimal turbulence and mechanical crushing in a physiological setting.