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.

Between August 8, 1985 and April 1, 1988, 100 patients in 22 centers underwent Symbion Total Artificial Heart (TAH) (Symbion, Inc., Salt Lake City, Utah) implantation as a bridge to cardiac transplant. Thirty patients received the Symbion J7-100, and 70 patients received Symbion J7-70 implants. Eighty-seven patients were men and 13 were women; mean age was 42 years, and mean weight was 73 kg. The time spent on the device ranged from 1 to 243 days, for a mean of 23 days. Sixty-eight patients underwent cardiac transplantation, with a 69% 30-day survival rate and a 46% (31 of 68) long-term survival rate. The majority of the patients had ischemic (52) or idiopathic (36) cardiomyopathies. Indications for implantation of the TAH occurred most frequently in patients whose condition deteriorated while awaiting transplant (34) or who were admitted in acute cardiogenic shock (27). There was an 8.7% incidence of thromboembolic events (four cerebrovascular accidents, five transient ischemic attacks). Multivariant analysis was performed to determine the effect of various factors on the patients' ability to undergo transplantation and then ultimate survival. The results indicate a need for further clinical investigation in patient selection and appropriate timing for implantation of the TAH.

MODERATOR COPELAND: I think we all as surgeons and allied personnel have a love-hate relationship with the coagulation system.It seems to me I spend most of my time trying to stop bleeding.We have this morning a learned panel to discuss bleeding and anticoagulation.First I would like to introduce them.On your right is Dr William DeVries, who, of course, needs no introduction, a pioneer in the total artificial heart.Next to him is Laurence Harker, who is chief of the Division of Thrombosis and Arteriosclerosis at the Scripps Clinic and has been an advisor to us on the national cooperative study of aspirin and coronary artery bypass grafting.He is certainly a platelet specialist.

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.

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.

One hundred sixteen total artificial hearts (TAH) were implanted in 113 patients by 29 centers between April 4, 1969 and March 1, 1988. Five were permanent and 111 were temporary implants (3 patients received second implants). Eight different types of TAHs have been used. The ages ranged from 15 to 62 (mean age: permanent 57, temporary 42). Sixty-seven percent (72/108) of patients receiving the TAH for temporary support were transplanted; 6 patients were waiting for a transplant. Forty-seven percent (34/72) were alive after transplantation. Of the 92 patients receiving the Jarvik TAH (the most frequently used device) as a temporary device, 67% (62/92) were transplanted (6 currently supported) and 55% were alive after transplantation; 85% were back to work, with a normal life-style. The thromboembolic rate for patients who received the device as a temporary support was 10%, with 3 patients having residual sequellae. No deaths resulted from mechanical failure. Experience to date suggests that the use of the TAH as a temporary device can be beneficial if patients are carefully selected.

THE EVOLUTION of the total artificial heart (TAH) from animal experimentation to clinical research has necessitated major changes in the control of the drive equipment responsible for prosthesis function. Our experience with patients who have been permanent recipients of the heart has contributed to a refinement of the operating protocol and furthered understanding of the hemodynamic response to artificial circulation devices. PROSTHESIS DESIGN The basic design of the pneumatic TAH has changed little since early animal experimentation and still incorporates a flexible diaphragm inside a semirigid housing.1-3In the Jarvik-7-100 (Symbion, Inc, Salt Lake City) ventricles, which constitute the device under discussion herein, polyurethane polymer (Biomer, Ethicon Inc, Somerville, NJ) is molded with Dacron polyester mesh to form the semirigid housing. Four layers of Biomer each 0.18 mm in thickness constitute the inflatable diaphragm. Graphite powder between the diaphragm layers deters creation of a flexion crease, which could lead

THE FIRST total artificial heart was implanted in a dog by Akutsu and Kolff1in 1957; this device sustained life for six hours. Since then, animal survival times with the artificial heart have increased dramatically, and refinements in the mechanics of the device have resulted in the development of an effective, gentle blood pump operated by a hemodynamically responsive drive system.2,3 Human use of a total artificial heart occurred initially in 1969 and again in 1981.4,5Cooley performed these first two implants as an interim measure until orthotopic cardiac transplantation could be accomplished. His efforts were followed by the first implantation of an artificial heart as a permanent replacement for the human heart in 1982.6,7By the end of 1986, a total of five permanent implant procedures had been accomplished, and 38 devices had been implanted as a bridge to transplantation.8,9As technological advances result

THE PRESS came into the operating theater 20 years ago when Christiaan Barnard, MD, electrified the world by performing the first human heart transplant. Since then, physicians with a "spectacular" medical case have found themselves, their patients, and their projects in the unwavering spotlight of the press. In our media-intrusive society, the spectacular case confronts physician-researchers with dilemmas unknown to their professional forebears. If the research happens to be conducted in the United States, the problems—or opportunities—tend to be intensified. American press organizations are unique in that their freedom to report news is guaranteed by the national constitution, and freedom and protection from previous restraint cannot be limited by government. Legislation and judicial decisions during the past quarter century have tended to make reporters' access to information easier, and citizens' recourse in libel actions more difficult. Consider these factors in relation to a spectacular, newsworthy medical case, especially one where

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.

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)

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.

The degree of red cell destruction in human recipients of the total artificial heart has not previously been described. Fifteen patients implanted with a Jarvik-7 total artificial heart for either temporary or permanent heart replacement were reviewed. Clinically significant elevations of plasma free hemoglobin and serum lactate dehydrogenase were demonstrated in patients receiving the standard (100 ml) Jarvik-7 containing Medtronic-Hall valves and powered by pulses of compressed air delivered at a dP/dT of 6000 mm Hg/sec to 8000 mm Hg/sec. Reduction of the dP/dT by drive unit modification greatly reduced the plasma free hemoglobin and lactate dehydrogenase in subsequent patients. Introduction of the smaller (70 ml) total artificial heart was not associated with greater hemolysis once dP/dT had been reduced. With the current driver delivering systolic pulses at less than 4500 mm Hg/sec, both size hearts are free of clinically relevant hemolysis. In addition, it appears that attempts to eliminate hemolysis completely by lowering heart rates, cardiac outputs, or driving pressures are potentially dangerous. The eventual development of embolic cerebrovascular accidents is associated statistically with heart rates below 80 beats/min. These data reassure implanting physicians that the updated Jarvik-7 total artificial heart system does not induce worrisome hemolysis. In addition, this study has uncovered a link between eventual cerebrovascular accident and low heart rate, implying that purposeful application of heart rates around 100 beats/min may provide a significant margin of protection against cerebrovascular accident during implantation.

The Jarvik-7 total artificial heart has been implanted in 18 patients at the time of this writing. Eleven patients received the 100 ml heart, and the remaining seven were treated with the 70 ml device. To date, five patients have been implanted for permanent use with an average survival in excess of 9 months, and the longest survival is more than 1 1/2 years following implantation of the heart. Complications related to positioning were a contributing factor in the death of one patient. Thirteen patients have received the Jarvik-7 heart as a bridge to transplant. Three died before transplant, and the remaining ten have been transplanted. To date, all are alive, several are home and in excellent condition, and several are still hospitalized but are expected to be released shortly. Three patients have experienced serious complications after transplantation. One patient rejected her heart transplant, was reimplanted with the artificial heart, and now has been sustained for more than 3 months. At this time she is in good condition awaiting a second donor. Selection of the appropriate size Jarvik-7 artificial heart for the individual patient can best be made based on measurements of thoracic dimensions obtained from a computed tomography scan and calculation of body surface area. The appropriate medial or lateral positioning can be determined and decisions concerning the lengths of the grafts and cuffs, excision or nonexcision of the left pericardium, and air drive line position can be made. The Jarvik-7 heart can be successfully used in patients from 50 kg. However, at the lower size limit in patients from approximately 50 to 65 kg, the risk of fit complications is the greatest and availability of an even smaller model heart would be desirable.