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Over the last 8 years, we have developed and evaluated a continuous-flow total artificial heart (CFTAH) comprising two rotary blood pumps. To understand the physiologic effects of nonpulsatile circulation, we evaluated the CFTAH in 65 calves for 90 days or less. We describe our experience with 29 calves that survived for 7 days or more. The calves received dual axial-flow (n = 24) or centrifugal-flow (n = 5) pumps. Several iterations of customized atrial cuffs were developed to facilitate an adequate anatomical fit. Pressures (arterial pressure [AoP], pulmonary artery pressure [PAP], left atrial pressure [LAP], and right atrial pressure [RAP]) and pump parameters were continuously monitored. Hematologic and biochemistry values were analyzed. After each case, a necropsy was performed. The calves survived for 7-92 days (mean, 24 days). Pressures were 94 ± 14 (AoP), 25 ± 8 (PAP), 14 ± 6 (RAP), and 16 ± 6 (LAP) mm Hg. Pump flow was maintained at 9.1 ± 1.7 L/minute (right) and 9.4 ± 1.9 L/minute (left). Hematologic and biochemistry values remained acceptable. Eight animals underwent treadmill evaluations, in which oxygen consumption (VO2) was comparable with physiologic total-body VO2. In the two animals that survived to 90 days, the end-organs appeared unremarkable at autopsy, and the CFTAH circuits were free of thrombus. Our results show that a CFTAH can maintain a large animal physiologically and hemodynamically for up to 90 days with continuous flow.

We evaluated the effects of steady state flow and perfusion on end-organ function in a long-term calf model. The animal received a continuous-flow total artificial heart (CFTAH) that we created from two axial-flow ventricular assist devices. Pump flow, blood pressure, and other pump parameters were monitored throughout the study, as were arterial blood gas and hematologic values, including neurohormone levels. Some hematologic values were mildly abnormal transiently after surgery but returned to acceptable levels within the first week. During the 90-day study, the calf showed no signs of hemolysis or thrombosis. Its mental function remained normal, as evidenced by the animal's interest in its surroundings and response to stimuli. End-organ and vasomotor function was not adversely affected by 90 days of steady state flow. This was the first study in which CFTAH support of an animal model was maintained for this duration.

Background We used contrast pericardiography during fluoroscopy to facilitate intrapericardial navigation in pigs. Methods In 8 juvenile pigs, we performed standard, noncontrast-enhanced fluoroscopy of the heart in an attempt to identify the location of the left and right atrial appendages, the atrioventricular (AV) groove, the coronary sinus, the superior and inferior vena cavae, and the right ventricular outflow tract. Then we injected ionic contrast into the pericardial space and repeated fluoroscopy. A subjective scoring sheet was used to grade the fluoroscopic image. Guided by the enhanced image, we placed a cardiac restraint device (CRD) around both ventricles. After 4 weeks, the pigs were humanely euthanized, and we examined the position of the CRD to verify that we had correctly identified the AV groove as well as the gross and histologic effects of intrapericardial contrast on the heart. Results Cardiac structures that were not visible on standard fluoroscopy could be delineated with substantially better clarity after intrapericardial injection of contrast. Postmortem examination showed that the CRD was positioned correctly at the AV groove and that contrast pericardiography was not associated with adverse topical effects. Conclusions Contrast pericardiography is a technique that greatly enhances one's ability to visualize the location and configuration of cardiac structures. We used this technique to accurately locate the AV groove and to aid us in the successful placement of a CRD. Improved fluoroscopic visualization of intrapericardial structures may facilitate the development of limited access and percutaneous intrapericardial interventions.

Although current continuous-flow total artificial hearts (CFTAHs) are much smaller than previous models, venous kinking may still occur after device implantation, especially in smaller animals. By inserting a self-expanding stent at the site of venous narrowing in a sheep model implanted with a CFTAH, we were able to restore the normal venous geometry and dramatically increase the CFTAH output. Because this percutaneous approach avoids the challenges associated with reoperation in these cases, it may be useful to other CFTAH investigators.

OBJECTIVE: To increase applicability and stability of aortic valve repair, a three-dimensional aortic annuloplasty ring has been developed for intra-annular placement. The goal of this study was to test the safety of this device with in vivo implantation in the calf model. METHODS: In 10 chronic calves, the HAART annuloplasty ring was sutured to the aortic valve annulus using cardiopulmonary bypass. The animals were recovered and followed for 1–2 months. Serial echocardiography was used to evaluate valve competence, and contrast aortograms and CT angiograms were obtained in selected animals. After completion of follow-up, each animal was euthanized, and aortic endoscopy was performed under water distension in five. Full autopsies with histologic examinations were performed. RESULTS: All animals survived surgery. Two were euthanized in the first week for complications, and the remaining eight calves were followed uneventfully for the 1–2 months. Serial echocardiography showed completely competent valves in all but one animal, in which the ring was intentionally up-sized to test the sizing strategy. Contrast aortographic and CT angiographic findings were similar to the echocardiograms. Postmortem examination showed proper seating of all rings with endothelialization at 1–2 months. All valves demonstrated good leaflet coaptation and no abnormalities. CONCLUSIONS: In vivo testing of a three-dimensional aortic annuloplasty ring in a chronic calf model proved to be very successful and safe. Using the sizing and implant strategies developed, human trials seem indicated.

We evaluated the in vivo performance of the Innovamedica pneumatic ventricular assist device (VAD), a new prototype of a simple, low-cost device for hospital circulatory support programs. We implanted the Innovamedica VAD in 6 sheep (weighing 55 to 91 kg). The inflow cannula was placed in the left ventricle, and the outflow cannula was anastomosed to the descending thoracic aorta. After heparinization (3mg/kg), we initiated the pump and monitored its hemodynamic performance for 6 hours. In a subsequent study we implanted the device for left ventricular support in two sheep for a 30-day period. We evaluated device performance based on implantation procedure, hemodynamic performance, and hematological impact. We monitored hematological and biochemical variables, and we assessed hemolysis. In the short-term experiments, the pumps maintained a mean blood flow of 4.4 ± 0.8 L/min. During support, mean arterial blood pressure was 76 ± 15 mmHg. The overall average concentration of plasma free hemoglobin was 5.11 ± 0.6 mg/dl compared with a baseline value of 4.52 ± 0.7 mg/dl. In the 30 day trials, mean blood output was 4 l/min ± 0.2, plasma free hemoglobin was 5.9 ± 4 mg/dl for the 30 day period excluding the first 48 hours. Warfarin/Aspirin anticoagulation was used after the first 72 hours with an average INR of 2.9 for the entire test period. Post-mortem showed no blood clots or any significant tissue damage to brain, lungs or kidneys. The devices operated without any significant adverse events in all of the experiments. The Innovamedica VAD was easy to implant and de-air and was found to be effective, reliable and biocompatible.

The development and clinical use of continuous-flow left ventricular assist devices (LVADs) stimulated our interest in developing a total heart replacement with continuous-flow rotary blood pumps. We constructed a continuous-flow total artificial heart (CFTAH) from 2 HeartMate II axial-flow LVADs and used this CFTAH to replace the native heart of a calf. The purpose of this experiment was to study the effects of total continuous flow on physiologic parameters at rest and during exercise after the animal recovered from surgery. We monitored pulmonary and systemic pump performance, and we assessed arterial blood gases, hemodynamic and biochemical variables, and neurohormone levels during the 7 weeks of CFTAH support. At day 36 after CFTAH implantation, the calf was exercised on a treadmill at increasing speeds for 40 minutes; total oxygen consumption, pump flow, blood pressure, and respiratory rate were monitored. Baseline hematologic levels were altered postoperatively but returned to normal by 2 weeks. We saw no signs of hemolysis or thrombosis during CFTAH support. The calf had a normal physiologic response to treadmill exercise. The animal gained weight and appeared to function normally during the study. The CFTAH operated within design specifications throughout the study. Homeostasis, end-organ and vasomotor function, and the ability to exercise are not adversely affected by 7 weeks of totally pulseless circulation in a calf.

Chronic ventilatory support may be required for survival after total artificial heart (TAH) implantation in calves. However, prolonged or repeated intubation may negatively affect a calf's ability to eat, drink, ruminate, and stand after surgery. To mitigate these limitations, we performed tracheotomies on 23 consecutive calves at the time of TAH implantation. The tracheostomies served as the primary route for ventilatory support and airway management. Tracheostomies were left in place for up to 25 days (mean, 7 +/- 7 days) and were well tolerated. Prolonged presence of a tracheostomy facilitated cleaning of the airway secretions and did not inhibit the calf's ability to stand, eat, or drink. The calves survived from 2 to 49 days (mean, 8 days). Twenty-two calves that maintained their tracheostomies died of causes unrelated to airway management. The calf that had the tracheostomy removed on day 25 died of respiratory arrest on day 49. At necropsy, we found that severe tracheal stenosis had developed at the tracheostomy site. In calves, an elective tracheotomy can be a valuable adjunct to TAH implantation or other procedures that might require prolonged ventilatory support or airway access, but care should be exercised if the tracheostomy is removed to ensure that the calf does not develop late tracheal stenosis.