Intracellular pH and role of Na+/H+ exchange during ischaemia and reperfusion of normal and diabetic rat hearts

STUDY OBJECTIVE: The aim was to investigate the role of intracellular pH (pHi) and ion exchange on the functional recovery of perfused hearts isolated from normal (N) rats either receiving or not receiving amiloride (an Na+/H+ exchange inhibitor), and from STZ induced diabetic (D) rats with decreased Na+/H+ exchange activity. DESIGN: Working heart preparations were submitted to a zero flow ischaemic period of 30 min at 37 degrees C and then reperfused for 30 min. The time course of pHi decline during ischaemia and of recovery on reperfusion was followed by means of 31P-NMR. MEASUREMENTS AND MAIN RESULTS: In N hearts without amiloride, ischaemia caused a progressive decrease in pHi. This was slightly, although not significantly, more abrupt in N hearts receiving amiloride. D hearts showed a slower fall in pHi, but the mean value reached after 30 min did not differ significantly from that of normal hearts. pHi recovery on reperfusion was markedly slower in the D hearts compared to N hearts. The mean value reached after 30 min did not differ significantly from that of N hearts. pHi recovery was also markedly slower in N hearts exposed to amiloride during both ischaemia and reperfusion. The higher functional recovery on reperfusion, as assessed by the recoveries of aortic flow and stroke volume, was observed for those hearts with slower pHi recovery. Improved recoveries of aortic flow and stroke volume as compared to normal non-treated hearts were 34% and 21% for the diabetic hearts, and 22% and 40% for the normal hearts receiving amiloride. CONCLUSIONS: The comparison of data from diabetic rat hearts with reduced activity of the Na+/H+ exchange process v normal hearts with pharmacological block of the exchanger provide support for a critical role of the Na+/H+ exchanger in the initial stage of reperfusion.