OKT3-induced hypotension in heart allograft recipients treated for steroid-resistant rejection

OKT3 (a murine antihuman mature T cell antibody) has become an important therapeutic agent for the treatment of acute allograft rejection unresponsive to corticosteroid therapy. Seven heart allograft recipients received eight 10-day courses (one retreatment) of OKT3 for steroid-resistant rejection. All patients underwent hourly monitoring of vital signs, and one of the patients underwent hemodynamic monitoring during therapy. Age- and sex-matched kidney allograft recipients (including one retreated patient) undergoing the identical OKT3 antirejection protocol served as control patients. All patients had a measured decrease in arterial pressure during OKT3 therapy. The time from first dose to peak hypotensive response was identical in both heart and kidney allograft recipients (31 ± 11 versus 32 ± 11 hours, respectively, p = not significant [NS]) and did not coincide with the peak febrile response (22 ± 12 versus 27 ± 13 hours, respectively, p = NS). The decrease in mean arterial pressure was significantly greater in the heart allograft patients compared with the kidney allograft recipients (39 ± 17 versus 22 ± 10 mm Hg, respectively, p < 0.03), despite a slightly greater positive fluid balance in the heart allograft recipients (1333 ± 1991 versus 715 ± 1224 ml, p = NS). The change in heart rate associated with the hypotension was only slightly and not significantly greater in the kidney allograft recipients. In the one heart allograft recipient undergoing hemodynamic monitoring, the decrease in mean arterial pressure was initially paralleled by a decline in systemic vascular resistance. Later, however, a proportionally greater decline in arterial pressure was produced by a combination of low systemic vascular resistance with a superimposed decrease in cardiac output. The decrease in cardiac output was not associated with a decline in pulmonary wedge pressure. It is postulated that the hypotension associated with OKT3 is produced by systemic vasodilation in all patients receiving the drug for acute rejection. The substantially greater decrease in arterial pressure in heart allograft recipients may be related to a combination of a reduced chronotropic response in the denervated heart plus a possible and currently unexplained depression of myocardial function.