Lack of inotropic effect of cyclosporin A in isolated guinea pig left atria

Abstract

Cyclosporin A is being widely used to prevent graft rejection in organ transplantation and to treat autoimmune diseases. Since various toxic side effects have been observed, the aim of this study was to look for even a subtle deleterious effect of cyclosporin A on cardiac inotropy in electrically stimulated guinea pig left atria. The left atrial muscles of guinea pigs, in Tyrode's solution containing 2.7 or 5.4 mM potassium, were electrically stimulated by one of two methods: (1) continuously at 3 Hz, during which cyclosporin A was applied cumulatively (from 10(-9) to 10(-5) M); or (2) stimulated intermittently at 2.5 Hz in 5 mM cyclosporin A, with rest periods of 4 s duration interposed every 4 min. The effects of cyclosporin A on contractile force were observed for 150 min in the first stimulation method, and the effects on the steady state contractile force and amplitude of post-rest contraction were observed for 240 min in the second method. The steady state contractile force of the atria declined within the 4 h period at 2.7 mM potassium in Tyrode's solution both in the cyclosporin A group (n = 10) and in the control group (n = 5) to 68(SD 11)% and to 63(4)%, respectively. After 4 h the amplitudes of the post-rest contraction were 101(16)% and 101(4)% in cyclosporin A and control groups, respectively. At 5.4 mM potassium, the following values were obtained (cyclosporin A v control): steady state force 70(8)% (n = 11) v 69(8)% (n = 5); post-rest force 105(9)% v 102(7)%. Cyclosporin A does not influence the steady state contractile force or the amplitude of the post-rest contraction, suggesting the absence of inotropic effects on isolated guinea pig left atria.