Transplantation of an unpaired organ, the heart.

The advent of clinical cardiac transplantation has been accompanied by a public fanfare unprecedented in medicine. This unfortunate situation has tended to obscure the long history of experimental heart transplantation and the relationship of clinical heart transplantation to previous work in renal and hepatic homotransplantation. This discussion is a review of past experimental work with a note on current clinical results at Stanford University Hospital. A decade ago three principal obstacles to orthotopic homotransplantation of the heart were easily identified in the laboratory: (1) difficulties in the development of a satisfactory surgical technique; (2) demonstration of adequate post-transplantation function of the heart in the absence of central nervous system influence; and (3) method for control of the homograft rejection phenomenon. No consideration of human application would be acceptable without the prior resolution of these three problems in the laboratory. Surgical Technique.-In 1959 the concept of atrial-to-atrial anastomosis for cardiac transplantation rather than multiple venous anastomoses was developed and successfully applied. Preservation of the heart during the obligatory period of anoxia was accomplished by simple immersion in cold saline to reduce the metabolic requirement. Safe ischemic time ranged up to six hours in the experimental laboratory, and routine survival of the host animal was achieved. Cardiopulmonary bypass was used to support the recipient. Performance Characteristics of the Heart Transplant.-Immediately after cardiac transplantation a diminution in cardiac output was noted for 24 to 48 hours. After the third day, values for cardiac output increased to the normal range. Ablation of normal regulatory mechanisms was reflected by an absence of respiratory sinus arrhythmia, an increased plasma volume, a decreased diuretic response to saline loading, and absence of the Bainbridge reflex. In the exact physiological replica of the homograft minus the immune reaction, the cardiac autograft, definite evidence of both vagal and sympathetic reinnervation could be detected one year postoperatively. Physiological impairment secondary to heart transplantation appeared to be temporary and minimal, and one could speculate that if the subject survived long enough, cardiac reinnervation might occur even across the homograft barrier. Control of the Homograft Rejection Phenomena.-The orthotopic homotransplanted heart was then studied histologically and electrocardiographically in the experimental laboratory to correlate changes in the cardiogram wvith pathologic lesions. Two kinds of pathologic lesions were simultaneously rioted; one was a cellular destruction of myocardium, and the second was a direct attack on the vascular endothelium. Rejection was invariably accompanied by myocardial edema and could be detected through examination of the electrocardiogram. The QRS amplitude regularly diminished starting about four days before death in animals undergoing cardiac rejection. Using the electrocardiogram as an early herald of homograft rejection, we obtained prolonged survival of animals