Alteration of Intracellular Na+During Ischemia in Diabetic Rat Hearts: The Role of Reduced Activity in Na+/H+Exchange Against Stunning

To elucidate the contribution of reduced activity of Na+/H+exchange in streptozotocin-induced diabetic hearts against stunning, intracellular Na+concentration ([Na+]i) was measured in isolated rat hearts using23Na-MRS. The recovery of left ventricular developed pressure in hearts reperfused after 15 min global ischaemia at 37°C was significantly better in diabetic ones (102.9±2.0% of pre-ischemic level, mean± ,n=6;P<0.05), and non-diabetic ones pre-treated with potent Na+/H+exchange inhibitor, EIPA (1μmol/l; 93.8±2.3%,n=5; *P<0.05) than non-treated, non-diabetic hearts (75.1±2.5%,n=8). When diabetic hearts were pre-treated with EIPA, the recovery (101.2±2.6%,n=5) was identical to that of non-treated, diabetic hearts. [Na+]iin non-diabetic hearts increased to 329.1±8.1% of pre-ischemic level during 15 min ischemia, whereas the increase in [Na+]iin diabetic hearts significantly suppressed to 199.8±10.3% (P<0.001). EIPA attenuated the increase of [Na+]iduring ischemia to 189.1±9.0% in non-diabetic hearts (P<0.001) and to 155.3±4.6% in diabetic hearts (P<0.05). Thus, the EIPA-dependent Na+accumulation during ischemia, i.e. Na+influx probably mostly via Na+/H+exchange was smaller in diabetic hearts by 69.7% compared with that in non-diabetic hearts. These results indicate that the cardiac protection against stunning in streptozotocin-induced diabetic hearts is mediated by the attenuation of Na+accumulation during ischemia, which is caused by the reduced activity in Na+/H+exchanger.