Inhibition of Na+/H+ exchange at the beginning of reperfusion is cardioprotective in isolated, beating adult cardiomyocytes

C. HURTADO AND G. N. PIERCE. Inhibition of Na+/H+ Exchange at the Beginning of Reperfusion is Cardioprotective in Isolated, Beating Adult Cardiomyocyt es. Journal of Molecular and Cellular Cardiology (2000) 32, 1897-1907, Stim ulation of Na+/H+ exchange during ischemia-reperfusion results in cardiac d amage. However, it is unclear whether the Na+/H+ exchanger is active during the ischemic period or during reperfusion. Adult beating cardiomyocytes we re exposed to an ischemia mimetic solution for 90 min and then reperfused w ith a normal solution for 30 min, 5-(N,N-dimethyl)-amiloride (DMA), a block er of the Na+/H+ exchanger, was administered during ischemia and the first 3 min of reperfusion or only during the first 3 min of reperfusion. Adminis tration of DMA only upon reperfusion resulted in increased cell survival (8 1 +/- 1%, P < 0.05) compared to using the drug during ischemia and reperfus ion (63 +/- 3%) and in the absence of drug (60 +/- 1%). During ischemia, pH , was lower when DMA was present in the ischemic solution, The inhibition o f the Na+/H+ exchanger retarded the recovery of pH during reperfusion. The highest recovery of active cell shortening was observed when DMA was used a t the beginning of reperfusion. The use of DMA also reduced the level of pa ssive cell shortening during reperfusion, and when used at the beginning of reperfusion significantly increased the recovery of Ca2+ transients. Our r esults demonstrate that the exchanger is primarily active during reperfusio n and that inhibition of the exchanger solely at this time has a strong car dioprotective effect. (C) 2000 Academic Press.