EFFECT OF VERAPAMIL ON THE CALCIUM PARADOX

Abstract

Reperfusion of isolated rat hearts with Ca-containing medium after a short period of Ca-free perfusion causes irreversible cell damage (Ca paradox). Experiments were undertaken to determine whether the slow-channel Ca-antagonist drug verapamil protects Ca-deprived rat heart muscle against the consequences of readmitting Ca. Cell damage was quantitated in terms of creatine kinase (CK) release, depletion of endogenous creatine phosphate (CP) and ATP stores, development of contracture as measured by longitudinal shortening of the left ventricle and ultrastructural damage. Verapamil (1 mg/l) did not reduce the initial rate of CK release during perfusion with Ca but reduced the initial rate at which myocardial CP and ATP stores were depleted and decreased the shortening of the longitudinal axis of the left ventricle. After 30 s of reperfusion the mean sarcomere length was significantly greater in the verapamil-treated hearts. Inhibition of Ca influx via the slow channels does not protect heart muscle against the deleterious effects of readmitting Ca after a period of Ca-free perfusion.