Report of a Heart Transplant Operation*

DONALD Ross, M.B., CH.B

London, England

T HE FOLLOWING is a report on the heart

transplant operation carried out in the

National Heart Hospital, London, England,

May 3, 1968.

CASE REPORT

The recipient, a 45 year old white man previ- ously in good health, had four documented at- tacks of myocardial infarction between May 1965 and January 1966. He had been unable to work for two years and had had 22 hospital admissions for coronary insufficiency and congestive heart fail- ure during this period. Before operation he could walk slowly for 100 yards and was restricted by pain and breathlessness. Nocturnal dyspnea was frequent, and on admission he had signs of heart failure, with raised jugular venous pressure, car- diomegaly, a reversed split of the second heart sound and a third heart sound. Coronary arterio- grams showed a blocked right coronary artery 3.5 cm. from the origin, a blocked anterior descending left coronary artery and a dilated circumflex artery. Left ventricular angiography confirmed the pres- ence of a dilated poorly contracting left ventricle. The electrocardiogram revealed sinus rhythm and left bundle branch block. After intensive medical treatment he had no peripheral edema, his jugular venous pressure was not raised and his liver was impalpable immediately prior to operation. The blood pressure was 120/90 mm. Hg, and there was no evidence of peripheral vascular disease.

The criteria for selection of a donor were ABO blood group compatibility and acceptable tissue compatibility in a young person who had been in good health before death. These criteria were ful- filled in a 25 year old man who had suffered irre- versible head injuries after a 20 foot fall and whose electroencephalogram had been flat for 24 hours.

On May 3, 1968, the heart transplant operation was carried out with the Lower-Shumway technic employing normothermic bypass. The total ischemic period of the donor heart was 35 to 40 minutes. Bypass was initially terminated with some difficulty: the right atrium distended, and the right

ventricle did not contract well. Bypass was re- started and an isoproterenol drip set up. With slow weaning the atria regained their tone, and bypass was terminated the second time without trousble. Total bypass time was 105 minutes.

After the operation stringent sterile conditions were maintained until the twenty-fourth day, when they were partially relaxed. The patient was treated with prophylactic antibiotics (gentamycin and clox- acillin) for the first three days after operation.

Zmmunosuppression was based on azathioprine, 200 mg. daily (3 mg./kg. body weight) and 10 mg. of prednisone twice daily. This treatment was started immediately after operation, and in the first 24 hours the patient also received 800 mg. of hydrocortisone. No antilymphocytic serum was used. It was decided to increase the dose of azathio- prine and steroids only if evidence of rejection was thought to be present. The criteria on which this decision was made were:

1. Signs of organ failure, demonstrated by low cardiac output, raised venous pressure, the pres- ence of a third heart sound and breathlessness. Diminished exercise tolerance, demonstrated by diminution in the ability to perform repetitive straight leg raising.

2. Systemic manifestations of rejection, shown by fever, general malaise and markedly diminished appetite.

3. Laboratory investigations showing a fall or a failure of the platelet count to rise at the expected time postperfusion and an increase in uridine in- corporation into RNA in peripheral blood lympho- cytes. Decreased electrocardiogram voltage, increase in blood sedimentation rate and changes in differ- ential white cell count did not prove helpful.

Two possible rejection episodes were treated, the first on the sixth, the second on the twenty- eighth day. The prednisone and azathioprine were increased according to the regimen described by Mowbray et al.1 The response to treatment was rapid and dramatic on the first occasion and less marked on the second.

Following operation the patient recovered con- sciousness immediately and was extubated early

# From the Department of Surgery, National Heart Hospital, London, England. Address for reprints: Donald Ross, M.B., National Heart Hospital, Westmoreland St., L.ondon, W. 1. England.

838 THE AMERICAN JOURNAL OF CARDIOLOGY

Report of Human Heart Transplant Operation 839

next morning. The donor heart was in sinus rhythm, and the recipient atria continued to con- tract independently. The patient could not in- crease his rate in response to exercise or failure until the fourteenth day after operation and needed isoproterenol in very small amounts to maintain a rate between 80 and 90/min. until then. In the first 24 hours his blood pressure was labile. in response to movement but thereafter was al- ways in the normal range (130 to 140/75 to 90 mm. Hg). He was maintained on digoxin from the sec- ond postoperative clay. Diuretics were necessary in the first fortnight and after the thirty-second day. From the sixth day his condition improved steadily so that by the twenty-sixth day he was in an ex- cellent clinical state with no evidence of heart failure and was able to lead a normal life with normal exercise tolerance within the confines of his room. On the twenty-eighth day, however, oc- casional atria1 and ventricular ectopic beats were noted; on the thin:y-third, T wave inversion was present in the left chest leads, and on the thirty- sixth day he had atria1 tachycardia soon followed by atria1 fibrillation.

Although there was some radiographic suggestion of pulmonary infarction on the fourth day and electrocardiographic evidence of right ventricular hypertrophy on the ninth, it was not until the thirty-sixth day after operation that unequivocal signs of pulmonary embolism were present. He then had a pleura,1 rub and coughed up fresh blood-stained sputum. He suddenly collapsed on the thirty-eighth day and was hypotensive, tachy- pneic and cyanosed with a profound metabolic acidosis. Jaundice and anuria followed, and his condition deteriora-ied until he died on the forty- fifth day.

At postnortem er:amination multiple pulmonary emboli, both large and small, were found in both

lungs. The largest measured up to 9 by 6 by 3 cm., and they were related to thrombotic emboli in the medium-sized and small pulmonary artery branches. Several large antemortem thrombi were present in the recipient right atria1 appendage. They were in the form of thin curved layers loosely adherent to the atria1 wall. The thrombi were not attached to the line of atria1 anastomosis, nor were they im- mediately adjacent to that line.

COMMENT

In future transplant operations we intend to introduce two major changes:

1. Since the cause of death in our patient was multiple pulmonary embolism originating from the recipient right atria1 appendage, we intend to remove as much of the recipient atria as possible; on evidence of pulmonary embo- lism, treatment with anticoagulants will be in- stituted.

2. Since we believe that definite episodes of rejection occurred, we intend to employ maxi- mal doses of azathioprine, steroids and anti- lymphocytic serum after operations and, as with other cadaver transplants, to institute some immunosuppressive treatment before transplantation also.

ACKNOWLEDGMENT

The patient was referred by Dr. S. Oram of King’s College Hospital.

REFERENCE

1. MOWBRAY, J. F., COHEN, S. L., DOAK, P. B., KENYON, J. R., OWEN, K., PERCIVAL, A., PORTER, K. A. and PEART, W. S. Human cadaveric renal transplanta- tion: Report of twenty cases. Brit. M. J., 2, 1387, 1965.

VOLUME 22, DECEMBER 1968