Role of Na+-Ca2+ exchange in the development of cardiac abnormalities due to calcium paradox.

Reperfusion of rat heart with Ca2+-containing medium for 1 to 10 min after a 5 min perfusion with Ca2+-free medium resulted in a generalized disruption of myocardial ultrastructure including swelling of sarcoplasmic reticulum and mitochondria, depletion of creatine phosphate and adenosine triphosphate stores, reduction of the microsomal but augmentation of the mitochondrial Ca2+ uptake activities and elevation of the cardiac Na+ as well as Ca2+ contents. These hearts developed contracture and were unable to generate contractile force. Lowering the concentration of Na+ from 145 to 35 mmol l-1 in the medium during Ca2+-free perfusion was observed to markedly reduce or prevent the reperfusion induced changes in myocardium. On the other hand, lowering the concentration of Na+ in the medium during the reperfusion phase following a 5 min perfusion with Ca2+-free medium enhanced the rate of depletion of the high energy phosphate stores and the rate of elevation of myocardial Ca2+ contents but markedly depressed the rise in Na+ contents. These results suggest that Ca2+-paradoxical changes in myocardium occur as a consequence of the intracellular Ca2+ overload in which Ca2+ entry through Na+-Ca2+ exchange mechanism at the cell membrane may be an important contributory factor.