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, intracellu lar pH (pH,) was measured by phosphorus-31 magnetic resonance spectros copy. Diabetes was induced by the injection of streptozotocin, The acc umulation of proton ion (Delta H+) during 15 min global ischemia at 37 degrees C was calculated from pH(i). There were no significant differ ences in Delta H+ between diabetic (DM: 0.54 +/- 0.03 mu mol/l, n = 6; mean +/- S.E.M.) and non-DM hearts (0.57 +/- 0.04, n = 6), when perfu sed with bicarbonate buffer, However, perfusion with HEPES buffer reve aled a significant increase of Delta H+ in DM (0.85 +/- 0.07, n = 5) c ompared with non-DM (0.61 +/- 0.06, n = 5: P<0.05). On the contrary, t he addition of a Na+/H+ exchange inhibitor (EIPA; 1 mu mol/l) to bicar bonate buffer significantly increased Delta H+ in non-DM (1.09 +/- 0.1 0, n = 4) compared with DM (0.71 +/- 0.03, n = 5; P<0.01). Perfusion w ith HEPES buffer and EIPA equally increased Delta H+ in both groups (D M 1.13 +/- 0.13, n = 4; non-DM 1.15 +/- 0.14, n = 4). Thus, the activi ty of Na+/H+ exchanger during ischemic acidosis, assessed as the incre ase of Delta H+ 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 Delta H+ between the bicarbonate buffer and the HEPES buffer was markedly bi gger in DM (0.31) than non-DM (0.04), These results indicate that Na+/ K+ exchange is a major mechanism to compensate ischemic acidosis in no n-DM hearts, whereas bicarbonate-dependent systems compensate the depr essed activity of Na+/H+ exchange in DM. (C) 1998 Academic Press