CYCLOSPORINE-ASSOCIATED REDUCTION IN SYSTOLIC MYOCARDIAL-FUNCTION IN THE RAT

The cardiotoxic effect of cyclosporine in the inbred rat was investigated in the isolated perfused heart model. Diastolic and systolic function was studied in 5 groups of (Lewis X Brown Norway)F1 rats treated with different doses of cyclosporine for different time intervals and in a group which received the vehiculum cremophor. Of the cyclosporine-treated rats, one group was studied four weeks after drug discontinuation to assess reversibility of the effect. To control for the nephrotoxic side effects of cyclosporine, a group of animals that had undergone 1.5-1.75 renal ablation was included. Left ventricular pressures were measured with a balloon catheter; stepwise increases in preload were obtained by small increments in the balloon volume. Over the range of left ventricular volumes studied, no differences were found in diastolic pressure between the groups. Peak systolic pressures were significantly lower in hearts obtained from cyclosporine treated rats which had received 15 or 7.5 mg/kg/24 h subcutaneously for three weeks (P < 0.05). Our results indicate that cyclosporine treatment resulted in a reversible decrease in myocardial contractile force apparently unrelated to decreases in renal function or to changes in mean arterial pressure.