Fukuta M, Wakida Y, Iwa T, Uesugi M, Kobayashi T
Third Department of Internal Medicine, Aichi Medical University, Japan.
Pacing Clin Electrophysiol. 1996 Nov;19(11 Pt 2):2027-33. doi: 10.1111/j.1540-8159.1996.tb03275.x.
The inhibition of Na(+)-H+ exchange (NHE) with amiloride analogues in vitro has been shown to prevent reperfusion arrhythmias and additional cell necrosis. Inhibition of intracellular Ca2+ overload via NHE inhibition has been suggested as a mechanism of these protective effects. The aim of this study was to examine whether treatment with amiloride analogues reduces the incidence of reperfusion arrhythmias and limits infarct size in vivo. Open-chest swine were exposed to a 30-minute left anterior descending artery (LAD) occlusion and 180 minutes of reperfusion during atrial pacing at 150 ppm. Intravenous 5-(N,N-dimethyl)-amiloride (AML, 5 micrograms/kg per min) was administered in the treatment group (n = 7) and intravenous saline in the control group (n = 7), starting 10 minutes before coronary occlusion. The infusion was continued during ischemia and reperfusion. The area at risk was defined by monastral blue dye and infarct size by triphenyltetrazolium chloride staining. Limb leads ECG and monophasic action potentials (MAPs) from the epicardium in the ischemic area were recorded. There was no significant difference in the size of the area at risk and hemodynamic parameters between the groups. However, the infarcted area was 0.4% +/- 1.0% of the area at risk in the treatment group, whereas it was 62% +/- 29% in the control group (P < 0.05). Pathological examination (Hematoxylin-eosin and Mallory's phosphotungstic acid-hematoxylin staining) revealed that all of the infarcted area consisted of contraction band necrosis. MAP duration in both groups was significantly shortened during ischemia. After reperfusion, MAP duration in the treatment group recovered earlier than that of control group. However, there was no significant difference in the incidence of ventricular tachyarrhythmia between the groups. Inhibition of NHE with AML prevented reperfusion related cell necrosis in the in vivo swine model, but did not reduce the incidence of ventricular tachyarrhythmia.
在体外，用氨氯地平类似物抑制钠氢交换（NHE）已被证明可预防再灌注心律失常和额外的细胞坏死。通过抑制NHE来抑制细胞内钙超载被认为是这些保护作用的一种机制。本研究的目的是检验用氨氯地平类似物治疗是否能降低体内再灌注心律失常的发生率并限制梗死面积。对开胸猪在心房以150次/分钟起搏的情况下进行30分钟的左前降支动脉（LAD）闭塞和180分钟的再灌注。治疗组（n = 7）静脉注射5-（N，N-二甲基）-氨氯地平（AML，5微克/千克·分钟），对照组（n = 7）静脉注射生理盐水，在冠状动脉闭塞前10分钟开始给药。在缺血和再灌注期间持续输注。危险区域用莫那司蓝染料界定，梗死面积用氯化三苯基四氮唑染色确定。记录肢体导联心电图以及缺血区域心外膜的单相动作电位（MAP）。两组之间的危险区域大小和血流动力学参数无显著差异。然而，治疗组梗死面积占危险区域的0.4%±1.0%，而对照组为62%±29%（P < 0.05）。病理检查（苏木精-伊红染色和马洛里磷钨酸苏木精染色）显示，所有梗死区域均由收缩带坏死组成。两组在缺血期间MAP持续时间均显著缩短。再灌注后，治疗组MAP持续时间比对照组恢复得更早。然而，两组之间室性快速心律失常的发生率无显著差异。在体内猪模型中，用AML抑制NHE可预防再灌注相关的细胞坏死，但并未降低室性快速心律失常的发生率
