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

A marked decrease in the activity of the amiloride-sensitive Na+/H+ ex changer has been demonstrated in hearts from streptozotocin (Sn)-induc ed diabetic rats. The aim of this study was to investigate the contrib ution of other specific sarcolemmal transport mechanisms to intracellu lar pH (pH(i)) recovery upon reperfusion in STZ-induced diabetic rat h earts and their relation to recovery of ventricular function. Isovolum ic 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) mechani sm contributed to pH(i) recovery after ischemia in the diabetic rat he arts. Even when the Na+/R(+) exchanger was blocked by amiloride in nom inally 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 ext ernal lactate and inhibited by alpha-cyano-4-hydroxycinnamate. This su ggested 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 stu dy shows that a good recovery of function occurred even more rapidly i n diabetic hearts receiving HEPES-buffered solution than in those rece iving HCO3--buffered solution. This suggests that the HCO3--dependent mechanism of regulation may be depressed in diabetic rat hearts.