Yamada K, Matsui K, Yamamoto S, Kitano M, Ohashi N
Sumitomo Pharmaceuticals Co., Ltd., Research Center, Osaka, Japan.
Int J Tissue React. 2002;24(1):1-10.
The effects of SM-20550 [N-(aminoiminomethyl)-1,4-dimethyl-1H-indole-2-carboxamide methanesulfonic acid], an Na+/H+ exchange inhibitor, on ischemic preconditioning (IPC) were studied in a rabbit model of myocardial ischemia and reperfusion injury. Anesthetized rabbits underwent occlusion of the coronary artery (30 min) followed by reperfusion (5 h). In SM-20550-treated animals, SM-20550 was intravenously administered at 0.03 mg/kg or 0.1 mg/kg before ischemia (30 min). Treatment with SM-20550 at 0.03 mg/kg had a nonsignificant tendency to reduce infarct size (18%). In contrast, 0.1 mg/kg of SM-20550 significantly reduced infarct size by 62%. In animals with IPC, the condition was induced by 2 or 5 min of ischemia and 10 min of reperfusion prior to sustained ischemia (30 min). Although 5 min of IPC significantly reduced infarct size by 72%, 2 min of IPC reduced infarct size by only 27%, which was not significant. The combination of 5 min of IPC and 0.1 mg/kg of SM-20550 significantly reduced infarct size by 78%. This reduction in infarct size was similar to that produced by 0.1 mg/kg SM-20550 or 5 min of IPC alone. Moreover, the combination of 2 min of IPC and 0.03 mg/kg of SM-20550 significantly reduced infarct size by 64%, although neither 0.03 mg/kg SM-20550 nor 2 min of IPC alone reduced infarct size significantly. These results indicate that an Na+/H+ exchange inhibitor SM-20550, does not antagonize the cardioprotective effect of IPC. SM-20550 and IPC appeared to act synergistically to exert a combined cardioprotective effect.
研究了钠氢交换抑制剂SM - 20550 [N -（氨基亚氨甲基）- 1,4 - 二甲基 - 1H - 吲哚 - 2 - 甲酰胺甲磺酸]对心肌缺血再灌注损伤兔模型缺血预处理（IPC）的影响。麻醉的兔子接受冠状动脉闭塞（30分钟），随后再灌注（5小时）。在SM - 20550治疗的动物中，在缺血前（30分钟）以0.03毫克/千克或0.1毫克/千克静脉注射SM - 20550。以0.03毫克/千克的SM - 20550治疗有减少梗死面积的趋势，但无统计学意义（减少18%）。相比之下，0.1毫克/千克的SM - 20550显著减少梗死面积达62%。在进行IPC的动物中，在持续缺血（30分钟）之前，通过2或5分钟的缺血和10分钟的再灌注诱导该状态。虽然5分钟的IPC显著减少梗死面积达72%，但2分钟的IPC仅减少梗死面积27%，无统计学意义。5分钟的IPC与0.1毫克/千克的SM - 20550联合使用显著减少梗死面积达78%。这种梗死面积的减少类似于单独使用0.1毫克/千克SM - 20550或5分钟IPC所产生的减少。此外，2分钟的IPC与0.03毫克/千克的SM - 20550联合使用显著减少梗死面积达64%，尽管单独使用0.03毫克/千克的SM - 20550或2分钟的IPC均未显著减少梗死面积。这些结果表明，钠氢交换抑制剂SM - 20550不会拮抗IPC的心脏保护作用。SM - 20550和IPC似乎协同作用以发挥联合心脏保护作用。
