MECHANISMS OF INTRACELLULAR PH REGULATION DURING POSTISCHEMIC REPERFUSION OF DIABETIC RAT HEARTS

A marked decrease in the activity of the amiloride-sensitive Na+/H+ exchanger has been demonstrated in hearts from streptozotocin (Sn)-induced diabetic rats. The aim of this study was to investigate the contribution of other specific sarcolemmal transport mechanisms to intracellular pH (pH(i)) recovery upon reperfusion in STZ-induced diabetic rat hearts and their relation to recovery of ventricular function. Isovolumic rat hearts were submitted to a zero-flow ischemic period of 28 min at 37 degrees C and then reperfused for 28 min. The time course of pH(i) decline during ischemia and of recovery on reperfusion was followed by means of P-31-labeled NMR. The perfusion buffers used were either HEPES or CO2/HCO3-. An HCO3--dependent (amiloride-insensitive) mechanism contributed to pH(i) recovery after ischemia in the diabetic rat hearts. Even when the Na+/R(+) exchanger was blocked by amiloride in nominally HCO3--free solution, a rapid rise in pH(i) occurred during the first 3 min of reperfusion. The early rise in pH(i) was reduced by external lactate and inhibited by alpha-cyano-4-hydroxycinnamate. This suggested that a coupled H+-lactate efflux may be a major mechanism for acid extrusion in the initial stage of reperfusion. The observation of a higher functional recovery on reperfusion in diabetic hearts is in accordance with previous studies using HCO3- buffer. However, this study shows that a good recovery of function occurred even more rapidly in diabetic hearts receiving HEPES-buffered solution than in those receiving HCO3--buffered solution. This suggests that the HCO3--dependent mechanism of regulation may be depressed in diabetic rat hearts.