Calcium paradox and calcium entry blockers

Abstract

Reperfusion of isolated hearts with calcium-containing solution after a short period of calcium-free perfusion results in irreversible cell damage (calcium paradox). This phenomenon is characterized by an excessive influx of calcium into the cells, the rapid onset of myocardial contracture, exhaustion of tissue high-energy phosphates, massive release of cell constituents, and extensive ultrastructural damage. The calcium paradox can be regarded as the most severe form of myocardial necrosis that can be produced experimentally. Under the experimental conditions described in this study, the calcium entry blockers verapamil, nifedipine, diltiazem and lidoflazine failed to reduce the massive release of enzymes that occurs in the severe form of the calcium paradox. Calcium entry blockers, however, may alter the time course of the events that occur during the development of the calcium paradox. Calcium entry blockers may have a protective effect in a mild form of the calcium paradox. This is of interest for cardiac surgery where calcium-free cardioplegic solutions are widely used. Calcium entry blockers may decrease the potential hazard of the use of these solutions.