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 using Na-23-MRS. The recovery of left ventricular developed pressure in hearts reperfused after 15 min global ischaemia at 37 degrees C was significantly better in diabetic ones (102.9 +/- 2.0% of pre-ischemic level, mean +/- S.E. n = 6; P<0.05), and non-diabetic ones pre-treated with potent Na+/H+ exchange inhibitor, EIPA (1 mu mol/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+](i) in non-diabetic hearts increased to 329.1 +/- 8.1% of pre-ischemic level during 15 min ischemia, whereas the increase in [Na+](i) in diabetic hearts significantly suppressed to 199.8 +/- 10.3% (P<0.001). EIPA attenuated the increase of [Na+](i) during 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. (C) 1998 Academic Press Limited.