Cardiac Transplantation

Organ Transplantation

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Cardiac Transplantation

O. H. Frazier, M.D., * and Denton A. Cooley, M.D. t

Transplantation of the heart began with a series of experimental studies by Carrel and Guthrie in 1905. 7 Clinical application became feasible following a series of eight canine orthotopic transplant procedures by Lower and Shumway in 1960. 23 Five of the recipient animals lived from 6 to 21 days. In December 1967, Christiaan Barnard shocked the world by performing the first human heart transplant in Capetown, South Africa. I Probably no event in the history of medicine has spurred such interest, accolades, and criticism. Others followed in rapid succession, including Shumway, who performed the first cardiac transplant operation in the United States, in January 1968,32 and Cooley, who performed the first successful heart transplant in the United States in May 1968Y Because of the seemingly overwhelming problems of rejection and infection that were encountered in these early attempts, the program was virtually abandoned. Shumway and colleagues at Stanford, however, maintained their interest, performing 227 cardiac transplant procedures in 206 patients from January 1968 to April 1981. 26 During 1968 and 1969 following the first successful transplant at the Texas Heart Institute, Cooley performed 23 heart transplant operations. 12 The 19ngest survival period in this series was 18 months. During the past decade, advances have been made in the clinical application of cardiac transplantation for patients with end-stage myocardial disease. 18 In the United States alone, 15,000 to 25,000 patients can now be considered potential transplant recipients. The addition in 1981 of cyclosporine as an adjunct to the immunosuppression necessary in the transplant patient has caused renewed interest in this method and has improved the long-term results of cardiac transplantation. 5, 6,19 Cyclosporine, an endecapetide extracted from fungi, appears to induce potent reversible preferential suppression of T lymphocytes while sparing the nonspecific immune system, A new program of cardiac transplantation was begun at the Texas

*Director.

Cardiac Transplantation Program, Texas Heart Institute; Associate Professor of Surgery, University of Texas Medical School, Houston, Texas tSurgeon-in-Chief, Texas Heart Institute; Clinical Professor of Surgery, University of Texas Medical School, Houston, Texas

Surgical Clinics of North America-Vo!' 66, No.3, June 1986

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Heart Institute in 1981 using this drug as the principal immunosuppressant. 13• 16 Since then, 74 heart transplant operations have been performed at our institution (as of July 17, 1985). In 1984, 440 heart transplants were performed in the United States. Problems associated with cardiac transplantation have not, however, completely disappeared with the introduction of cyclosporine. There are now 44 registered (with The International Heart Transplantation Registry, 1984) centers performing cardiac transplantation in the United States alone. Unless the federal government intervenes to make funds available only to certain designated transplant centers, that number is likely to increase. The proliferation is occurring at a time when funds for care of the ill are becoming increasingly limited. Despite improved results with cyclosporine, the care of the average heart transplant patient requires continued involvement by surgeons, cardiologists, pathologists, infectious disease specialists, social workers, and others. This represents a considerable and costly effort by any medical community. The social, moral, ethical, and legal implications of heart transplantation have been partially resolved with the acceptance of "brain death" as an indication that the life of a donor has ended. Most states in this country have adopted legislation supporting this concept, thus placing procurement and selection of donors on a more logical basis and firmer legal ground. Nevertheless, the procurement of donors as a source of allografts is and will remain a serious limitation for further application of cardiac transplantation, especially with the proliferation of transplant centers. This article discusses the major aspects of a program in clinical cardiac transplantation and focuses on our approach to management of attendant problems. PATIENT SELECTION Most patients referred for cardiac transplantation have end-stage heart failure due to coronary artery disease with global left ventricular dysfunction, idiopathic cardiomyopathy, or previously treated valvular heart disease associated with cardiomyopathy. They are generally in NYHA Functional Class IV, with a prognosis limited to weeks or months. Although it would seem that almost any patient facing imminent death from heart disease would be a candidate for transplantation, certain criteria have evolved to help centers evaluate candidates. Relative contraindications to transplantation include elevated pulmonary vascular resistance above 6 to 8 Wood units, active infection, recent pulmonary infarction, diabetes mellitus requiring insulin, marked obesity, severe peripheral vascular disease, significant renal disease greater than can be attributed to pre renal azotemia or hepatic congestion, unrelenting life-limiting conditions (malignant neoplasm), and psychosocial abnormalities that would prohibit posttransplantation rehabilitation. Transplantation can, however, be done in patients with one or more of these contraindications. The decision to proceed must be based upon clinical evaluation and judgment of the transplant team.

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During admission to the Texas Heart Institute, candidates are subjected to an in-depth evaluation, including a complete medical history, a physical examination, and laboratory studies (biochemical, microbiologic, hematologic, radiologic, and immunologic). Cardiac catheterization is performed with coronary arteriography to detect cardiac abnormalities and pulmonary vascular resistance. The patient's psychosocial status is then assessed. A supportive social structure with a history of medical compliance is important in determining which patients would be likely to adhere to strict postoperative guidelines. After the patient is accepted as a suitable candidate by the Medical Review Board, informed consent is obtained with a full discussion of current risks, complications, and expected survival of cardiac transplantation recipients. Patients are then placed on a waiting list. Transplantation is undertaken when an appropriate donor is matched, based on size and negative cross-match when feasible.

DONOR HEART SELECTION AND PROCUREMENT Donors should be between 15 and 35 years of age (40 years for women) with normal heart function as defined by electrocardiogram, physiologic performance, physical examination, and history. Potential donors should be scrutinized as thoroughly as time permits regarding status of cardiac function. The use of high doses of catecholamines such as dopamine should be discontinued, if possible, or at least reduced to 6 mg per kg per minute at the time the donor heart is harvested. Also included in the evaluation protocol are a sequential multiple analysis (SMA), chest roentgenogram, blood and urine cultures, and erythrocyte typing. Contraindications include obvious bacterial or viral sepsis, malignancy, primary heart disease, tuberculosis, systemic disease involving the heart, and chronic hypertension. Ventilatory support for less than 100 hours with normal gas exchange is required. , ., After brain death is established, appropriate studies of tissue compatibility are completed. The donor and recipient must be ABO compatible and reasonably comparable in terms of body weight with a negative crossmatch. Standard techniques are used to detect HLA determinants. 2o Cadaver hearts can be used even if donor-recipient antigenic differences in the HLA system are found. Recipients bearing three or four antigen identities or cross-reactivities with the cadaver donor are preferred. Explanted hearts can be stored and will support the circulation when reimplanted. 15, 17, 27, 28 The use of cold saline preservation was first applied to donor organ procurement by the Stanford group.4 Functional results were satisfactory in distant procured hearts, which encouraged other centers to use similar methods. 24 The limits imposed on the storage time depend upon the myocardial temperature, the supply of oxygen, and the amount of mural edema that accumulates. In practical terms, although preservation for up to 72 hours may be possible, preservation in saline from 3 to 4 hours at 4° C represents, at present, the limit of clinical usefulness (approximately 1,000-mile flight radius). In March 1984, we reported our experience with

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distant organ procurement. 30 Although ischemic times were substantially longer for the hearts procured from distant referral centers, all of these organs maintained the circulation at the end of implantation.

SURGICAL PROCEDURE Donor Donor cardiectomy is performed by means of a median sternotomy. After ligature and division of the superior vena cava, the inferior vena cava is clamped immediately above the diaphragm. When the heart becomes empty, the aorta is cross-clamped, and 500 ml of cold potassium cardioplegic solution are infused into the aortic root. The inferior vena cava is divided to decompress the heart. When arrest is complete, the heart is elevated, the pulmonary veins, aorta, and pulmonary artery are divided, and the heart is removed and rapidly immersed in saline solution at 4° C. The left and right atria and great vessels are then trimmed for implantation. The heart is placed in a plastic bag containing 500 ml of saline solution at 4° C, and this bag is placed in a larger bag with a similar volume of saline solution. The outer bag is then stored in a commercial cooler and surrounded with ice for the return trip. Recipient A median sternotomy incision is performed, and cannulation of the venae cavae is completed, placing the cannulas close to the atriocaval junction below the crista terminalis. 9 The catheter for arterial return is placed in the ascending aorta near the origin of the innominate artery. Following institution of cardiopulmonary bypass, tourniquets on the venae cavae are closed, and the ascending aorta is cross-clamped. The pulmonary artery may also be clamped to prevent air from entering the pulmonary circulation, but this is usually not necessary. The heart of the recipient is removed, leaving a shell posteriorly consisting of the right and left atria (Fig. lA). The allograft is then placed on the operating table, and implantation is begun (Fig. IB). The first anastomosis is accomplished between the left atria by using a continuous 3-0 monofilament polypropylene suture that extends around the entire circumference of the atria (Fig. Ie and D). The right atria are similarly connected with a continuous suture (Fig. IE). Endto-end anastomosis between the pulmonary artery first and then the ascending aorta is performed using 4-0 polypropylene sutures (Fig. IF). Air is aspirated from the cardiac chambers after caval tapes have been released. The clamp is then released from the ascending aorta, thus restoring cardiac circulation (Fig. IG). The donor heart, which has been without coronary circulation for 1 to 5 hours, then receives coronary flow and resumes cardiac activity. In some instances, ventricular fibrillation occurs initially, but this can be reversed by electrical countershock. Cardiac stimulants, including calcium chloride, digitalis, and even epinephrine, may be useful during the early phase.

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Temporary cardiac pacing wires should be inserted into the myocardium of the right ventricle. Heterotopic Transplantation Barnard has described a technique of heterotopic, or "piggy-back," cardiac transplantation. 25 In this technique, the allograft serves as an auxiliary to total heart bypass, connecting the donor heart in parallel with the recipient heart, or it may be implanted as a simple left ventricular bypass. 2 , 21, 22 In the former instance, the pulmonary artery of the allograft is placed in continuity with the main pulmonary artery of the recipient (Fig. 2). A preclotted woven Dacron graft is often needed as a conduit for the donor pulmonary artery to reach the recipient pulmonary artery without tension or distortion of the other anastomoses,lO, 14 The two left atria are connected. The superior venae cavae are joined, and the aorta is implanted into the ascending aorta. Flow to the donor or the recipient ventricle is related to the respective ventricular compliance. Blood is ejected asynchronously, depending on the heart rates. Normally, flow is greatest through the donor heart, since ventricular compliance is greater than in the recipient heart. We have used heterotopic implantation in three patients. In two of the patients, the recipient heart initially carried more flow until the donor heart recovered from ischemia. This technique has the advantage of preserving the heart of the recipient in the hope that it will continue to function in instances of irreversible, acute rejection or advanced graft arteriosclerosis from chronic rejection. 3 Heterotopic technique should not be used when the recipient has undergone previous valve replacement, because thrombosis of the prosthesis has been described. 8

PATIENT MANAGEMENT Cyclosporine is given orally (14 mg per kg) 4 to 5 hours prior to surgery. The dose is decreased if there is renal dysfunction. Postoperatively, cyclosporine is administered intravenously (2 to 4 mg per kg per day) as a continuous infusion until the patient is able to take fluids orally. Cyclosporine serum trough levels are measured daily with standard radioimmunoassay, and the level is maintained between 200 to 400 ng per ml by adjustments of the daily dosage. The recipients receive 0.5 gm of methylprednisolone intravenously at the time of cardiectomy and 125 mg intravenously every 8 hours postoperatively for 24 hours. Thereafter, prednisone is given orally starting at 120 mg the day after transplantation and tapered daily so that by 60 days after transplantation, the recipient is receiving 30 mg per day. After 2 months at this level, the dosage is tapered to 20 mg per day, achieved by the 120th day. Reverse isolation is not used. Care following transplantation is similar to care for conventional cardiac patients. Patients remain in the intensive care unit until they can be moved to the transplant unit (approximately 1 to 3 days). Discharge from the transplant unit is usually within 2 to 3 weeks. Patients require constant monitoring for infections and appropriate J

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Figure 1. A to G, Technical steps in cardiac transplantation. Asterisks denote the location of the sinoauricular nodes in the remnant of the recipient heart and in the allograft (see text). (From Cooley, D. A.: Techniques in Cardiac Surgery. Edition 2. Philadelphia, W. B. Saunders Company, 1984; with permission.) Illustration continued on opposite page

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Figure 1 (Continued).

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Figure 2. Technique used for heterotopic heart transplantation. A, Donor heart is prepared for implantation. Care must be taken to obtain an adequate length of superior vena cava. B, Donor and recipient hearts. The posterior portion of the left atrial anastomosis is begun. Illustration continued on opposite page

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Figure 2 (Continued). C and D, The atrial-caval anastomosis is done next, ensuring a widely patent communication. E, The aortic anastomosis is completed, with implantation of the donor aorta into the ascending aorta of the recipient. The recipient pulmonary artery is incised. F, A suitable length of Dacron graft is inserted between the donor and recipient pulmonary arteries to complete the pulmonary artery anastomosis.

treatment when necessary. Broad-spectrum antibiotics (cefotaxime sodium, 2 gm every 6 hours) are begun intraoperatively and continued until the chest tubes are removed. Management of Rejection Right heart catheterization and right endocardial biopsies are performed weekly during the first 4 weeks following transplantation and frequently during periods of rejection. To diagnose chronic rejection, we perform right- and left-sided heart catheterization with coronary angiography 1 year following transplantation and then at annual intervals. Clinical and histopathologic diagnosis of rejection is based on criteria developed at the Texas Heart Institute by McAllister. Rejection is graded on a scale of increasing severity from 1 to 10. Mild rejection is common and warrants no treatment if stable. Mild or moderate rejection with suboptimal cyclosporine levels may respond to adjustments of cyclosporine dosage. If there is evidence of myocyte damage and cyclosporine levels are therapeutic, intravenous steroids (1.5 to 3.0 gm) are given over a 24- to 72-hour period, followed by a cardiac biopsy 48 hours after the last dose. Lack of adequate clinical or histologic response is managed by intravenous infusions of equine antithymocyte globulin (ATG) at 7 mg per kg over 6 hours twice a day for 14 days.

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RESULTS The major transplant centers throughout the world report similar results, a consequence of experience and meticulous management of transplant recipients. In five centers (Papworth Hospital in Cambridge, Texas Heart Institute in Houston, La Pitie Hospital in Paris, University of Pittsburgh, and Stanford University) through August 1984, 334 patients received 337 heart transplants. The cumulative survival rate was 80 per cent at 1 year and 75 per cent at 2 years. There were 277 male (83 per cent) and 57 female (17 per cent) patients. Deaths in this series were attributed to allograft rejection, infection (related to immunosuppression), decreased cardiac performance, arrhythmia, multisystem organ failure, graft atherosclerosis, cerebral incidents, and malignancy. Complications frequently noted were diastolic hypertension, renal dysfunction, hepatic dysfunction, hirsutism, tremor, gingival hyperplasia, and pancreatitis. Between July 4, 1982, and July 15, 1985, 74 patients underwent cardiac transplantation (71 orthotopic, 3 heterotopic) at the Texas Heart Institute. The patients ranged in age from 8 months to 63 years (mean 42.4 ± 12.4 years). There were 62 male and 12 female patients. The indications for transplantation in these patients included ischemic cardiomyopathy in 31 (42 per cent), idiopathic cardiomyopathy in 28 (38 per cent), congenital heart disease in 7 (9 per cent), viral cardiomyopathy in 5 (7 per cent), and valvular heart disease in 3 (4 per cent). The patients have been followed for 1 month to 3 years (mean, 9 months). Of the 74 patients receiving transplants, 55 are alive and 19 are dead (7 from rejection, 9 from infection, 2 from arrhythmia, and 1 from other causes (nontransplant)). Thirteen (68 per cent) of the deaths occurred within 3 months after transplantation. All deaths (except the one nontransplant-related death) occurred within 6 months of transplantation. By actuarial analysis, the overall survival rate from 6 months through 36 months remained 70 per cent. At 1 year, freedom from rejection and freedom from fatal rejection were 22 per cent and 87 per cent, respectively; at 36 months, freedom from rejection had decreased to 11 per cent, but freedom from fatal rejection remained the same (87 per cent). Most rejection episodes were diagnosed 2 to 23 days postoperatively. Late rejection episodes (after 6 months) were frequently associated with low cyclosporine trough levels. All survivors who were discharged are in NYHA Functional Class I and have returned to previous occupations or activities. Infections are common in the immunosuppressed host. A high percentage of the patients treated for rejection subsequently developed infection, indicating the close relationship between infection and rejection. Infection was diagnosed in 72 per cent of our posttransplant patients, and 50 per cent of infections followed treatment of rejection. The bulk (60 per cent) of the infections were bacterial. 29 Most of the bacterial infections were pulmonary. Infections of the urinary tract, skin, gallbladder, and blood have also been seen. Enterobacteriaceae organisms and Staphylococcus aureus were the most common bacteria involved in these infections. 31 Twenty-five per cent of the episodes of infection were viral in origin, and most of the viral infections were caused by Herpes simplex. Fifteen per

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cent of all infections encountered were caused by fungal and protozoal organisms. Candida albicans has been the most common cause of fungal infections in our series .. At 5 to 36 months, the actuarial freedom from infection was 39 per cent, and freedom from fatal infection was 82 per cent. The statistically significant factors affecting survival are the age and sex of the recipient, the etiology of the recipient's cardiac failure, and the degree of tissue compatibility between the donor and the recipient. Serious episodes of rejection and infection were tolerated best by patients younger than 45 years of age at transplantation and by women recipients (p < 0.05). Ten of 12 female patients with transplants are alive. Mortality was lower in patients with idiopathic or rheumatic cardiomyopathy than in those with ischemic cardiomyopathy (p < 0.01). Other associated medical conditions, such as diabetes mellitus, infection, and pulmonary infarction, influenced morbidity but were not responsible for death in any of the patients. Four of our patients underwent cardiac transplantation following initial support with an intra-aortic balloon pump (IABP). One patient, a 22-yearold mother, was admitted with class IV postpartum cardiomyopathy, a cardiac index of 1.6, bilirubin of 8, and multiorgan failure. During the ensuing weeks, the patient developed ascites, congestive hepatic dysfunction (bilirubin of 38), and coma. An IABP was inserted, and 10 days later she was found to have Candida albicans and Streptococcus viridans septicemia and a positive urine culture for Escherichia coli. After 1 week, her blood cultures were positive for Staphylococcus aureus. A donor became available, and transplantation was performed successfully. One week after transplantation, she underwent cholecystectomy for acute gangrenous cholecystitis; the gallbladder was positive for Candida and Enterococcus. She recovered and was discharged and is alive and well 16 months after transplantation.

CONCLUSION Transplantation of the heart is a proven therapeutic modality for patients with end-stage heart disease. With careful patient selection and appropriate postoperative care, most patients can be assured a return to a normal lifestyle. Results may be influenced by patient selection and experience of the transplant team. We have done 25 transplants in patients between the ages of 20 and 40 and had only one death. Of the 19 deaths in our series of 74 heart transplants, 17 occurred in our first 43 patients. The procurement of suitable donors remains a continuing obstacle. Many qualified recipients die awaiting the arrival of a donor. We believe that every available donor heart should be utilized to allow end-stage cardiac patients a chance at life. From July 1984 to July 1985, 65 patients were approved for cardiac transplantation at the Texas Heart Institute. Fourteen of these patients died before a suitable donor organ could be located. Efforts to prolong the period that an allograft may be safely preserved outside the body should help alleviate some of the logistic problems that now exist and increase the availability and utilization of donor hearts.

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Cyclosporine has certainly improved the prognosis for patients and has been particularly helpful in reducing the incidence of fatal complications. However, complications from the drug (particularly renal and hepatic) occur, and close monitoring of the patient's serum levels with appropriate dose adjustments is necessary. Our ability to deal with these complications has improved with experience, flexibility in use of combinations of immunosuppressants, and a new system for determining rejection that has allowed us to be more selective in administration of immunosuppressants. Using, in some cases, relatively new antibiotics, antiviral and antifungal agents, we have successfully treated late cases of invasive Aspergillosis, Legionella, Pneumocystis, and Herpes. Cyclosporine properly used has allowed effective control of rejection without suppression of bone marrow function. Previously unmanageable infections have now become curable in some instances. The increased number of survivals seen in heart transplantation has resulted from meticulous management of patients in well-established transplant centers familiar with the many problems these patients incur. The major drawbacks of graft rejection and infection have been lessened but not eliminated. Although cardiac transplantation has become a viable therapeutic tool in the treatment of end-stage heart disease, its future depends on the continued development of safer and still more effective means of preventing allograft rejection.

REFERENCES 1. Barnard, C. N.: A human cardiac transplant. S. Afr. Med. J., 41:1271, 1967. 2. Barnard, C. N., and Losman, J. G.: Left ventricular bypass. S. Afr. Med. J., 49:303, 1975. 3. Barnard, C. N., Losman, J. G., Curcio, C. A., et al.: The advantage of heterotopic cardiac transplantation in the management of severe acute rejection. J. Thorac. Cardiovasc. Surg., 74:918, 1977. 4. Billingham, M. E., Baumgartner, W. A., Watson, D. C., et al.: Distant heart procurement for human transplantation: Ultrastructural studies. Circulation, 62(Suppl 1): 11, 1980. 5. Borel, J. F.: Immunosuppressive properties of cyclosporine A (CyA). Transplant. Proc., 12:233, 1980. 6. Borel, J. F., and Wiesinger, D.: Studies on the mechanism of action ofcyclosporine A. Br. J. Pharmacol., 66:66, 1979. 7. Carrel, A., and Guthrie, C. C.: The transplantation of veins and organs. Am. J. Med., 11: 1101, 1905. 8. Cohn, L. II.: Surgical treatment of valvular heart disease. Am. J. Surg., 135:444, 1978. 9. Cooley, D. A.: Techniques in Cardiac Surgery. Edition 2. Philadelphia, W. B. Saunders Company, 1984, pp. 369-372. lO. Cooley, D. A.: Techniques in Cardiac Surgery. Edition 2. Philadelphia, W. B. Saunders Company, 1984, pp. 372-374. 11. Cooley, D. A., Bloodwell, R. D., and Hallman, G. L.: Cardiac transplantation for advanced acquired heart disease. J. Cardiovasc. Surg., 9:403, 1968. 12. Cooley, D. A., Bloodwell, R. D., Hallman, G. L., et al.: Cardiac transplantation: General considerations and results. Ann. Surg., 169:892, 1969. 13. Cooley, D. A., Frazier, O. H., and Kahan, B. D.: Cardiac transplantation with the use of cyclosporine A for immunologic suppression. Tex. Heart Inst. J., 9:247, 1982. 14. Cooley, D. A., Romagnoli, A., Milam, J. D., et al.: A method of preparing woven Dacron grafts to prevent interstitial hemorrhage. Cardiovasc. Dis. Bull. Tex. Heart Inst., 8:48, 1981.

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15. Cooper, D. K. C.: The donor heart. The present position with regard to resuscitation, storage and assessment of viability. J. Surg. Res., 21:363, 1976. 16. Frazier, O. H., Cooley, D, A., Painvin, G. A., et al.: Cardiac transplantation at the Texas Heart Institute: Comparative analysis of two groups of patients (1968-1969 and 19821983). Ann. Thorac. Surg., 39:303, 1985. 17. Guerraty, A. J.: Prolonged preservation of the isolated canine heart. Heart Transplantation, 1 :9, 1981. 18. Jamieson, S. W., Oyer, P. E., Reitz, B. A., et al.: Cardiac transplantation at Stanford. Heart Transplantation, 1 :86, 1982. ( 19. Kahan, B. D.: Cyclosporine A: A new advance in transplantation. Tex. Heart. Inst. J., 9:253, 1982. 20. Kerman, R. H., and Kahan, B. D.: Immunological evaluation of transplant rejection: Pre and postoperative indices detecting immune responsiveness. Ann. Clin. Res., 13:244263, 1981. 21. Losman, J. G.: Review of the Cape Town experience with heterotopic cardiac transplantation. Cardiovasc. Dis. Bull. Tex. Heart Inst., 4:243, 1977. 22. Losman, J. G., and Barnard, C. N.: Hemodynamic evaluation of left ventricular bypass using a homologous cardiac graft. J. Thorac. Cardiovasc. Surg., 74:695, 1977. 23. Lower, R. R., and Shumway, N. E.: Studies in orthotopic homotransplantation of the canine heart. Surg. Forum, 11:18, 1960. 24. Mendez-Picon, G. J., Goldman, M. H., Wolfgang, T. C., et al.: Long-distance procurement and transportation of human hearts for transplantation. Heart Transplantation, 1:63, 1981. 25. Novitzky, D., Cooper, D. K. c., and Barnard, C. N.: The surgical technique of heterotopic heart transplantation. Ann. Thorac. Surg., 36:176, 1983. 26. Pennock, J. L., Oyer, P. E., Reitz, B. A., et al.: Cardiac transplantation in perspective for the future: Survival, complications, rehabilitation, and cost. J. Thorac. Cardiovasc. Surg., 83:168, 1982. 27. Proctor, E.: Preservation of the dog heart for 96 hours at 4° C. Br. J. Surg., 58:306, 1971. 28. Proctor, E., Matthews, G., and Archibald, J.: Acute orthotopic transplantation of hearts stored for 72 hours. Thorax, 26:99, 1971. 29. Reece, I. J., Painvin, G. A., Chandler, L. B'., et al.: Infection after cardiac transplantation: Treatment and prognosis. Tex. Heart Inst. J., 11:38, 1984. 30. Reece, I. J., Painvin, G. A., Okereke, O. U. J., et al.: Evolution of the Texas Heart Institute distant organ procurement program. Tex. Heart Inst. J., 11 :38, 1984. 31. Reece, I. J., Painvin, G. A., Zeluff, B., et al.: Infection in cyclosporine-immunosuppressed cardiac allograft recipients. Heart Transplantation, 3:239, 1984. 32. Shumway, N. E., Dong, E., Jr., and Stinson, E. B.: Surgical aspects of cardiac transplantation in man. Bull. N.Y. Acact Med., 45:387, 1969. Texas Heart Institute P.O. Box 20345 Houston, Texas 77225