Kusuoka H, Matsuda S, Ishikawa M, Koga K, Mori T, Yamaguchi H, Nishimura T
Division of Tracer Kinetics, Biomedical Research Center, Suita, Osaka, Japan.
J Mol Cell Cardiol. 1998 Aug;30(8):1643-9. doi: 10.1006/jmcc.1998.0729.
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 (DeltaH+) during 15 min global ischemia at 37 degreesC was calculated from pH i. There were no significant differences in DeltaH+ between diabetic (DM: 0. 54+/-0.03 micromol/l,n=6; mean+/-s.e.m.) 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 DeltaH+ 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; 1 micromol/l) to bicarbonate buffer significantly increased DeltaH+ 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 DeltaH+ 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 DeltaH+ 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 DeltaH+ 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.
为了阐明糖尿病心脏和非糖尿病心脏在缺血性酸中毒期间碱化机制的差异，通过磷-31磁共振波谱法测量细胞内pH值（pHi）。通过注射链脲佐菌素诱导糖尿病。根据pHi计算37℃下15分钟全心缺血期间质子离子（ΔH +）的积累。当用碳酸氢盐缓冲液灌注时，糖尿病（DM：0.54±0.03μmol/l，n = 6；平均值±标准误）和非糖尿病心脏（0.57±0.04，n = 6）之间的ΔH +没有显著差异。然而，用HEPES缓冲液灌注显示，与非糖尿病心脏（0.61±0.06，n = 5，P<0.05）相比，糖尿病心脏（0.85±0.07，n = 5）的ΔH +显著增加。相反，在碳酸氢盐缓冲液中添加Na + /H +交换抑制剂（EIPA；1μmol/l）后，与糖尿病心脏（0.71±0.03，n = 5，P<0.01）相比，非糖尿病心脏（1.09±0.10，n = 4）的ΔH +显著增加。用HEPES缓冲液和EIPA灌注两组的ΔH +均增加（糖尿病组1.13±0.13，n = 4；非糖尿病组1.15±0.14，n = 4）。因此，在缺血性酸中毒期间，通过向碳酸氢盐缓冲液中添加EIPA诱导的ΔH +增加来评估的Na + /H +交换体活性，非糖尿病心脏（0.52）高于糖尿病心脏（0.17）。相反，通过碳酸氢盐缓冲液和HEPES缓冲液之间的ΔH +差异评估的碳酸氢盐依赖性系统的贡献，糖尿病心脏（0.31）明显大于非糖尿病心脏（0.04）。这些结果表明，Na + /H +交换是补偿非糖尿病心脏缺血性酸中毒的主要机制，而碳酸氢盐依赖性系统补偿糖尿病心脏中Na + /H +交换体活性的降低。
