The contrasting effects of cyclosporin-A and azathioprine on arterial blood pressure and renal function following cardiac transplantation.

The effects of cyclosporin-A and azathioprine on the postoperative development of systemic hypertension and renal dysfunction in patients undergoing cardiac transplantation were compared retrospectively in 18 patients receiving cyclosporin-A and in 12 patients receiving azathioprine. Twelve months postoperatively, the average mean blood pressure was 116 +/- 13 mm Hg and 98 +/- 7.5 mm Hg; the average preoperative serum creatinine was 1.2 +/- 0.3 mg% and 1.5 +/- 0.3 mg%; and the postoperative serum creatinine was 2.2 +/- 0.8 mg% and 1.1 +/- 0.2 mg% (P less than 0.0001) in the cyclosporin-A-and azathioprine-treated groups respectively. Hemodynamic studies were done to characterize the de novo postoperative hypertension developing in the cyclosporin-A group. The pre- and postoperative cardiac output was 3.7 and 4.91/min, respectively (P less than 0.01). The pre- and postoperative systemic vascular resistance was 1707 and 1941 dynes sec X cm-5, respectively (P greater than 0.2). Peripheral renin activity and 24-hour urinary catecholamine excretion were not elevated. The mechanism of the hypertension developing in cyclosporin-A-treated patients is unknown, but is associated with normalization of cardiac output, an abnormally elevated systemic vascular resistance, and modest impairment of renal function. These findings are in marked contrast to azathioprine-treated patients, in whom postoperative hypertension and renal dysfunction do not occur. These observations implicate cyclosporin-A as the major contributing factor in the development of hypertension and renal dysfunction.