STUDY ON THE ROLE OF Na_+-H_+ EXCHANGE ON ISCHEMIA-REPERFUSION INjURY

阿米洛利类似物在体外抑制Na<@D1+@> H<@D1+@>D1交换（NHE）已被证明可防止再灌注心律失常和额外的细胞坏死。通过NHE抑制来抑制细胞内Ca<@D12+@> D 1过载被认为是这些保护作用的机制。本研究的目的是检查阿米洛利类似物治疗是否能降低再灌注心律失常的发生率并限制体内梗死面积。开胸猪暴露于左前降支动脉闭塞30分钟和再灌注180分钟，心房起搏150 ppm。在方案1中，治疗组（n=7）在冠状动脉闭塞前10分钟静脉注射5-（N，N-二甲基）-阿米洛利（AML）5 μ g/kg/min，对照组（n =7）静脉注射生理盐水。在方案2中，在再灌注前5 min静脉推注AML 1 mg/kg，然后在治疗组（n=7）中以5 mug/kg/min静脉推注，在对照组（n=7）中以5 mug/kg/min静脉推注。 ...更多信息 对照组（n=8）。两个方案中，治疗组和对照组之间的危险区大小和血流动力学参数均无显著差异。然而，梗塞面积为0.4（±）SY。[)1.0方案1的治疗组中的风险面积为62%，而方案1的治疗组中的风险面积为62%。[)29%（P<0.05）。方案2治疗组的梗死面积也明显小于对照组（10.3 ± 0.5mm）。[)7.1% vs.42.3（]SY. ±.（18.8%，p<0.05）。病理检查显示梗塞区均为收缩带样坏死。两组再灌注后室性心律失常的发生率无显著差异。在体内猪模型中，抑制AML的NHE防止了再灌注相关的细胞坏死。如果在缺血前给药，这种作用会增强。然而，即使在缺血后（再灌注前）给药，梗死面积也显著减少。在该实验模型中，两种方案对再灌注心律失常均无影响。少

The inhibition of Na<@D1+@>D1-H<@D1+@>D1 exchange (NHE) with amiloride analogues in vitro has been shown to prevent reperfusion arrythmias and additional cell necrosis. Inhibition of intracellular Ca<@D12+@>D1 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 arrythmias and limits infarct size in vivo. Open-chest swine were exposed to a 30 min left anterior descending artery occlusion and 180 min reperfusion during atrial pacing at 150 ppm. In protocol 1, intravenous 5-(N,N-dimethyl)-amiloride (AML) 5mug/kg/min was administered 10 min before coronary occlusion in the treatment group (n=7) and intravenous saline in the control group (n=7). In protocol 2, an intravenous bolus injection of AML 1mg/kg was performed 5 min before reperfusion and followed by 5mug/kg/min intravenous injection in the treatment group (n=7) and saline in the … More control group (n=8). There was no significant difference in the size of the area at risk and hemodynamic parameters between the treatment ans control groups both in the protocols. However, the infarcted area was 0.4(]SY.+-。[)1.0% of the area at risk in the treatment group of the protocol 1, whereas it was 62(]SY.+-。[)29% in the control group (p<0.05). The infarcted area in the treatment group of the protocol 2 was also significantly smaller than that in the control group (10.3(]SY.+-。[)7.1% vs.42.3(]SY.+-。[)18.8%, p<0.05). Pathological examination revealed that all of the infarcted area consisted of contraction band necrosis. There was no significant difference in the incidence of ventricular arrhythmias after reperfusion between the groups in the protocols. Inhibition of NHE with AML prevented reperfusion related cell necrosis in the in vivo swine model. This effect was augmented if the drug was administered before ischemia. However, even if the drug was administered after ischemia (before reperfusion), there was significant reduction of the infarcted area. In this experimental model, there was no effect on reperfusion arrhythmia in the both protocols. Less