Difference in the Mechanisms for Compensating Ischemic Acidosis in Diabetic Rat Hearts

To elucidate the difference in the mechanisms for alkalization during ischemic acidosis between diabetic and non-diabetic hearts, intracellular pH (pHi) was measured by phosphorus-31 magnetic resonance spectroscopy. Diabetes was induced by the injection of streptozotocin. The accumulation of proton ion (ΔH+) during 15 min global ischemia at 37°C was calculated from pHi. There were no significant differences in ΔH+between diabetic (DM: 0.54±0.03μmol/l,n=6; mean± ) and non-DM hearts (0.57±0.04,n=6), when perfused with bicarbonate buffer. However, perfusion with HEPES buffer revealed a significant increase of ΔH+in DM (0.85±0.07,n=5) compared with non-DM (0.61±0.06,n=5P<0.05). On the contrary, the addition of a Na+/H+exchange inhibitor (EIPA; 1μmol/l) to bicarbonate buffer significantly increased ΔH+in non-DM (1.09±0.10,n=4) compared with DM (0.71±0.03,n=5P<0.01). Perfusion with HEPES buffer and EIPA equally increased ΔH+in both groups (DM 1.13±0.13,n=4; non-DM 1.15±0.14,n=4). Thus, the activity of Na+/H+exchanger during ischemic acidosis, assessed as the increase of ΔH+induced by addition of EIPA to bicarbonate buffer, was higher in non-DM (0.52) than DM (0.17). In contrast, the contribution of bicarbonate-dependent systems evaluated by the deference of ΔH+between the bicarbonate buffer and the HEPES buffer was markedly bigger in DM (0.31) than non-DM (0.04). These results indicate that Na+/H+exchange is a major mechanism to compensate ischemic acidosis in non-DM hearts, whereas bicarbonate-dependent systems compensate the depressed activity of Na+/H+exchange in DM.