The effect of verapamil on the calcium paradox

Abstract

Reperfusion of isolated rat hearts with calcium-containing medium after a short period of calcium-free perfusion results in irreversible cell damage (calcium paradox). Experiments were undertaken to determine whether the slow-channel calcium-antagonist drug verapamil protects calcium-deprived rat heart muscle against the consequences of readmitting calcium. Cell damage was quantitated in terms of creatine kinase (CK) release, depletion of endogenous creatine phosphate (CP) and adenosine triphosphate (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 reperfusion with calcium 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 seconds of reperfusion the mean sarcomere length was significantly greater in the verapamil-treated hearts. These results can be interpreted to mean that inhibition of calcium inflex via the slow channels does not protect heart muscle against the deleterious effects of readmitting calcium after a period of calcium-free perfusion.