Evaluation of total artificial heart performance in man.

This report describes the method whereby total artificial heart (TAH) performance was evaluated in the first human implantation, the operating characteristics of the TAH and the accompanying circulatory response. The patient survived for 112 days. Weekly averages (+/- standard deviation) for left-heart drive pressure ranged from 146 +/- 5 to 171 +/- 10 mm Hg, right-heart drive pressure from 46 +/- 4 to 79 +/- 17 mm Hg, heart rate from 77 +/- 8 to 98 +/- 3 beats/min, diastolic vacuum from 0 to 7 +/- 0.5 mm Hg and percent systole 40 +/- 1 to 44 +/- 0. Left-sided cardiac output ranged from 3.0 +/- 0.4 to 3.9 +/- 0.2 liters/min/m2, and was consistently greater than right-sided cardiac output, which ranged from 2.6 +/- 0.4 to 3.6 +/- 0.1 liters/min/m2. Drive line air pressure and flow signals and cineradiography of the TAH demonstrated complete filling and ejection for the left ventricle and complete filling but partial ejection for the right ventricle. There was no significant change in cardiac index during variation in right atrial pressure between 4 and 14 mm Hg. During 21 days of invasive hemodynamic monitoring, daily average of mean systemic arterial pressure ranged from 81 +/- 5 to 107 +/- 11 mm Hg, pulmonary artery pressure from 22 +/- 2 to 28 +/- 8 mm Hg and left atrial pressure from 8 +/- 2 to 22 +/- 4 mm Hg. Prominent V waves on the left atrial pressure tracing suggested mitral regurgitation as a cause of the difference between the outputs of the 2 ventricles.(ABSTRACT TRUNCATED AT 250 WORDS)

The role of nuclear medicine in three permanent total artificial heart recipients.

A total of 13 nuclear medicine studies were performed on three permanent total artificial heart (TAH) recipients at Humana Hospital-Audubon. Preoperative radionuclide studies were performed to evaluate left ventricular function for all three patients. Contrast studies were contraindicated because of impaired renal function. Two of the patients had renograms to assess renal function. The two patients who had strokes received 111In Oxine-labeled platelet scans to determine the presence of thrombi in the atria or TAH. No thrombi were evidenced. At autopsy, several septic thrombi were found, none of which contained a detectable amount of platelets.

Thromboembolic and infectious complications of total artificial heart implantation.

Thromboembolic and infectious events were found to be major complications of long-term total artificial heart implantation in two patients. Similar complications have been reported in other patients, as well as in animal studies. The thromboembolic events and the infectious complications appear to be interrelated. On the one hand, thrombi located on the valves and at the vascular anastomoses of the artificial heart were found to be infected at autopsy; such infections are known to exacerbate formation of thromboemboli. On the other hand, the generation of microthrombi may have contributed to the RES blockade seen in our patients. We hypothesize that this RES blockade led to a progressive decrease in lymphoid system function and impaired the patients' capacity to clear microorganisms from the circulation. These phenomena arose, in part, from the design of the artificial heart and were exacerbated by associated therapy, such as blood transfusions. Our data suggest several measures that might be taken in order to reduce the severity of both the thrombogenic and infectious complications. Improved anticoagulation regimens, which increase the ability of the physician to maintain the proper balance between thrombotic and hemorrhagic potential, are needed. This may require not only improved methods of monitoring anticoagulation and predicting changes in the effectiveness of various agents as other events supervene, but also new anticoagulant and antithrombotic drugs, for example, low molecular weight heparins and prostacyclin derivatives. It is also clear that the design of the artificial heart should be modified in order to improve fluid dynamics so that they will approximate as closely as possible those of the natural heart. This includes redesigning the mounting of the valves to eliminate crevices and discontinuities that allow stagnant flow and predispose to thrombus formation as well as imposing a dP/dt that minimizes shear-related hemolysis, thereby minimizing the need for blood transfusions. Prevention of infections presents a more difficult problem. Transcutaneous lines (regardless of their use) are an obvious route for infection, and attention should be given to minimizing the number and length of use of monitoring lines. However, until a totally implantable drive system is available, the drive lines will remain a potential avenue for the introduction of infections. The risk may be minimized by rigorous attention to care of the exit sites and by improved designs that will provide a better mechanical barrier by, for example, enhancing epithelial ingrowth into the materials of the drive line.(ABSTRACT TRUNCATED AT 250 WORDS)

Unilateral pulmonary emphysema created by ligation of the left pulmonary artery in newborn puppies.

The left pulmonary artery was ligated in 7 puppies 12 to 24 hours after birth. All were followed by periodic chest roentgenograms. At 6 months of age, ventilatory spaces, split-lung function, and static compliances were determined. Bronchograms and arteriograms were obtained, and histopathology was studied. All animals demonstrated a decrease in left lung size with gross and microscopic changes typical of chronic emphysema. There was impressive bronchial artery hypertrophy. Oxygen consumption and static compliances in the left lungs were depressed. These marked alterations in maturation, as well as the degenerative changes, are believed to be related to an impairment in the nutritive circulation of the lung.

Nutrition for the first Total Artificial Heart patient: implications for future patients.

Since the mid-1960s, millions of dollars in federal funds have been used for research in the development of the Total Artificial Heart (TAH). Significant advances in bio-materials and pump and energy systems, as well as animal experimentations, have led to the clinical reality of the TAH's use in man. On December 2, 1982, Dr. Barney Clark became the first recipient of a permanent TAH. He had been suffering from terminal congestive heart failure secondary to idiopathic cardiomyopathy. No other treatment was available, since, at the age of 61, he was too old for heart transplant. Dr. Clark's 112-day hospitalization was complicated by pulmonary problems, renal insufficiency, seizures, nosebleeds, and a broken heart valve. Dr. Clark appeared malnourished before surgery, and his numerous postoperative complications confounded attempts at nutritional support. Standard nutritional assessment techniques were inadequate or inappropriate in the face of severe edema, renal failure, and multiple transfusions. Although nitrogen balance was achieved intermittently, for the majority of his hospitalization Dr. Clark remained in negative nitrogen balance, due mainly to renal insufficiency. Some of the nutritional complications seen in the first TAH patient might have been preventable with early nutritional assessment and more aggressive support. The Artificial Heart Management Team at the University of Utah now includes a nutritionist, and future protocols outline detailed nutrition monitoring.

The role of nuclear imaging in the management of the first total artificial heart recipient.

On December 2, 1982, a permanent total artificial heart was implanted into the chest of a 61-year-old man with a progressive and irreversible cardiomyopathy. During the ensuing four-month hospitalization, a number of nuclear medicine procedures were obtained to assist in patient management. These procedures included gated cardiac radionuclide ventriculography, an I-123 iodoamphetamine scan for cerebral perfusion, and In-111 labeled leukocyte imaging. These radionuclide studies demonstrate the advantages of being able to monitor physiologic changes noninvasively and illustrate a potential role for nuclear cardiology in managing patients with a total artificial heart.

The physician, the media, and the 'spectacular' case.

KIE: Drawing on his experiences as a pioneer in performing artificial heart transplants for illustration, DeVries considers the dilemmas that the physician-researcher working on a "spectacular" medical case confronts in dealing with the news media. He discusses five major concerns: the patient's privacy; the effects of the media on the treatment of the patient; the integrity of the experiment; hospital disruptions; and the negative reactions of peers who perceive physician-researchers as self-aggrandizing. DeVries concludes that physician cooperation with the press is necessary and desirable, but that it should be based on the following principles: (1) concern for the patient and family is paramount, taking precedence over the public's right to know; (2) any information released must be accurate; and (3) advance preparation regarding the logistics of reporting the news quickly and accurately is essential.^ieng

The permanent artificial heart. Four case reports.

This article describes the clinical course of four patients in whom the Jarvik-7-100 total artificial heart was implanted as a permanent device. Details of their preoperative assessment and comprehensive summaries of their postoperative course are presented. The neurological, hematological, renal, and infectious complications they experienced and the interventions initiated to achieve resolution of these problems are described. Finally, revisions in the treatment protocols as a consequence of the experience and knowledge gained are examined.

Biomaterial-centered sepsis and the total artificial heart. Microbial adhesion vs tissue integration.

The principal barrier to the extended use of the total artificial heart is infection that is centered on the biomaterial constituting the prosthetic device and exacerbated by the surrounding damaged tissue. Ultrastructural studies of total artificial hearts removed from two patients indicate a failure of true tissue integration and diffuse, adhesive bacterial colonization of biomaterial surfaces. Biomaterials are, in part, susceptible to infection because, at the present state of the art, they are usually not well integrated with host tissue or, if hemodynamic, not optimally biocompatible or antiadhesive.

Postmortem microbiological findings of two total artificial heart recipients.

This report describes the postmortem microbiological findings and related gross pathology from two patients who had the longest survival after implantation of the Jarvik-7-100 total artificial heart. We documented extensive polymicrobial colonization at the site of the device and adjacent structures; however, the internal drive lines were remarkably free of bacterial colonization despite evidence of infection at the skin junction and in close proximity to the artificial heart. The polyurethane polymer (Biomer) on the external surface of the device was discolored and pitted in appearance and the Velcro material that attaches the two ventricles together was eroded. A nonspecific mass of tissue that was adherent to the device and to portions of the drive lines contained inflammatory cells, fibrinous debris, and colonies of microorganisms.

Immunologic complications of long-term implantation of a total artificial heart.

Bacterial infections are a significant complication of long-term total artificial heart implantation. We evaluated the functional capabilities of host defense mechanisms in two patients sustained long-term by a total artificial heart. Although serum complement and polymorphonuclear leukocyte function remained intact, both patients became B and T lymphopenic and there was an initial decrease in the ratio of helper/inducer to suppressor/cytotoxic cells. Histologic examination of their lymphoidal tissue at autopsy further revealed reduced numbers of germinal centers and atrophy of the T lymphocyte-dependent areas. In addition, the reticuloendothelial system was engorged with degenerate erythrocytes. We hypothesize that blockade of the reticuloendothelial system was induced by multiple blood transfusions necessitated by device-associated hemolysis and coagulopathy. This blockade may have led to a progressive loss of content of the antigen-specific lymphoidal elements and, perhaps, to a reduced ability to ingest microbe-antibody complexes.

Multigated radionuclide study of the total artificial heart.

A permanent total artificial heart, the Jarvik-7, was implanted into a 61-year-old male with a severe cardiomyopathy. Gated radionuclide studies were performed in the patient both prior to surgery and following implantation. Preoperative gated radionuclide cardiac studies revealed marked left ventricular enlargement, severe hypokinesis and a left ventricular ejection fraction of 10%. The right ventricle was moderately enlarged with a 27% ejection fraction. Following implantation of the Jarvik-7 artificial heart, gated cardiac studies were performed with a computer gated by a signal from the heart controller. The left ventricular ejection fraction was 69% and the right ventricular ejection fraction was 62%. This compared to a theoretical ejection fraction of 74% for each ventricle based on chamber anatomy. There was excellent ventricular emptying. Phase analysis showed uniform diaphragm motion. The use of gated cardiac studies in humans may prove helpful in evaluating mechanical problems with the artificial heart, such as malfunction of the diaphragm, before they become clinically apparent.

Cardiorespiratory interactions in patients with an artificial heart.

A retrospective analysis of the influence of respiration was carried out in three patients with artificial hearts. During spontaneous ventilation, large swings in intrathoracic pressure can produce a pattern reminiscent of pulsus paradoxus in the systemic arterial pressure. A decrease in intrathoracic pressure decreased biventricular filling and enhanced biventricular emptying. An increase in intrathoracic pressure increased biventricular filling, but acting as an increased afterload, impeded biventricular emptying. The influence of respiration on the artificial heart can be considered the result of the artificial ventricles' functioning effectively as extrathoracic pumps, such that changes in intrathoracic pressure produce gradients for biventricular filling and ejection relative to atmospheric pressure (which serves as the reference pressure for the artificial ventricles). Respiratory-induced variation in ventricular performance is clearly present with the artificial heart, but the mechanisms producing these changes appear to be markedly different from normal conditions, in which the ventricles are functionally within the thorax and have a compliant common septum allowing ventricular interaction.

Alterations in select immunologic parameters following total artificial heart implantation.

We examined select immunologic parameters in three recipients of a total artificial heart and correlated changes with the clinical course. Two patients remain alive and were studied for 320 and 240 days, respectively; the third died 10 days after implantation. All patients demonstrated transient complement activation immediately postoperatively, as indicated by an increase in plasma levels of C3a des Arg. In the two long-term survivors, C3a des Arg levels again increased, concomitant with intravascular hemolysis associated with high blood shear rates imposed by the drive system of the heart. All three patients had a marked lymphopenia immediately postoperatively, and the two long-term survivors demonstrated marked fluctuations in total lymphocyte count. There was a progressive decline in the number of peripheral blood helper/inducer T cells in the two long-term survivors. A large number of activated (HLA-DR positive) suppressor/cytotoxic T cells were also noted in these two patients. A progressive decrease in B cells was also observed; however, total IgG and IgM levels were not decreased. No changes in neutrophil phagocytic or respiratory burst capacities were identified. The cause of these changes in lymphocyte populations is not clear; however, they may have impact on the use of this device as a bridge to transplantation and may lead to decreased immunocompetence during long-term use.

Impact of regulations on artificial organs research.

From a research perspective, some of the primary problems created by the FDA regulations include: the amount of time necessary to comply with the regulations and to obtain FDA and IRB review of the studies. The cost of such delays may be great in terms of statistical death. Lack of understanding of the regulations on the part of investigators. Escalated costs and extra restrictions on the use of animals. Benefits of the regulations appear to be: better preclinical testing performed prior to initiating clinical trials, and improved testing protocols, both of which may result in lower risks to patients.

Response of the human body to the first permanent implant of the Jarvik-7 Total Artificial Heart.

The success of the first permanent total artificial heart implant would have been more obvious had the patient been able to be transferred from the hospital to an outlying home care setting. Nevertheless, several major achievements were realized. First, we were able to demonstrate that the total artificial heart will fit within an adult male chest without causing obstruction to inflow or outflow channels. Second, we were able to demonstrate that the total artificial heart would sustain life on a long-term basis (at least up to 112 days) without any evidence of systemic or local infection and without any untoward systemic effects. Third, we were able to demonstrate that the patient was able to tolerate a total artificial heart without complaint of the noise or the bulk of the drive system to which he required permanent attachment and that the patient could be comfortable and totally free of pain. An additional finding, which could not be assessed in the animal experimentations, was the fact that the patient was able to maintain higher CNS activity on an undisturbed basis following the implant of the total artificial heart. It is for these reasons that the entire University of Utah Medical Center staff feel great indebtedness to the patient and his family for demonstrating to the world the feasibility and the necessity for pursuing this device as a new therapy for end-stage heart disease.