Na+ overload during ischemia and reperfusion in rat hearts:: Comparison of the Na+/H+ exchange blockers EIPA, cariporide and eniporide

Na+ overload during ischemia and reperfusion in rat hearts:: Comparison of the Na+/H+ exchange blockers EIPA, cariporide and eniporide
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DOI:
10.1023/a:1024985931797
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发表时间:
2003-08-01
影响因子:
4.3
通讯作者:
van Echteld, CJA
van Echteld, CJA
中科院分区:
生物学3区
文献类型:
--
作者:
ten Hove, M;van Emous, JG;van Echteld, CJA

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缺血时心肌细胞内Na+超载是通过Na+/Ca 2+交换逆转再灌注损伤的重要原因。通过阻断不同的Na+内流途径可以防止Na+超载。在这项研究中,使用三种不同的Na+/H+交换器(NHE)阻断剂:EIPA、cariporide和eniporide,测试了NHE的缺血抑制对[Na+](i)、pH(i)和缺血后收缩恢复的影响。分别使用同步P-31和Na-23 NMR光谱法在起搏(5 Hz)的离体Langendorff灌注大鼠心脏中测量pH(i)和[Na+](i),同时通过心室内球囊评估收缩力。在30分钟的全脑缺血之前5分钟内给予NHE阻断剂(3 μ M),然后进行30分钟的无药物再灌注。NHE阻断显著降低缺血性Na+超负荷;缺血30分钟后,未治疗组和EIPA组的[Na+](i)分别增加至基线值的293+/-26,212 +/-6,157 +/-5,146 +/-6%(p
Intracellular myocardial Na+ overload during ischemia is an important cause of reperfusion injury via reversed Na+/Ca2+ exchange. Prevention of this Na+ overload can be accomplished by blocking the different Na+ influx routes. In this study the effect of ischemic inhibition of the Na+/H+ exchanger (NHE) on [Na+](i), pH(i) and post-ischemic contractile recovery was tested, using three different NHE-blockers: EIPA, cariporide and eniporide. pH(i) and [Na+](i) were measured using simultaneous P-31 and Na-23 NMR spectroscopy, respectively, in paced (5 Hz) isolated, Langendorff perfused rat hearts while contractility was assessed by an intraventricular balloon. NHE-blockers (3 muM) were administered during 5 min prior to 30 min of global ischemia followed by 30 min drug-free reperfusion. NHE blockade markedly reduced ischemic Na+ overload; after 30 min of ischemia [Na+](i) had increased to 293+/-26, 212+/-6, 157+/-5 and 146+/-6% of baseline values in untreated and EIPA (p