A Na⁺–H⁺ exchange inhibitor (SM-20550) protects from microvascular deterioration and myocardial injury after reperfusion

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• 作者：Ito ; Yuichi ; Imai ; Susumu ; Ui ; Goro ; Nakano ; Masayuki ; Imai ; Kunihiko ; Kamiyama ; Hiroshi ; Naganuma ; Fumio ; et. al.
• 关键词：Na⁺&ndash ; H⁺ exchange ; `No-reflow' phenomenon ; Coronary flow reserve ; Myocardial damage ; Arrhythmia ; Reperfusion
• 刊名：European Journal of Pharmacology
• 出版年：1999
• 出版时间：June 25, 1999
• 年：1999
• 卷：374
• 期：3
• 页码：355-366
• 全文大小：740 K

文摘

Na⁺–H⁺ exchange inhibitors may reduce myocardial damage after reperfusion. However, their effects on microvascular deterioration are not known. We examined the potency of a novel Na⁺–H⁺ exchange inhibitor, SM-20550 [N-(Aminoiminomethyl)-1,4-dimethyl-1H-indole-2-carboxamide methanesulfonate], and its effects on microvascular damage after reperfusion. In an in vitro study, the Na⁺-H⁺ exchange inhibiting activity of SM-20550 was about 10 times greater than that of ethylisopropyl amiloride. In in vivo experiments, we occluded the left circumflex coronary artery in 29 dogs for 2 h and then reperfused for 5 h. SM-20550 was administered either before ischemia (n=11) or before reperfusion (n=7). Another 11 dogs served as controls. We found that SM-20550 not only improved coronary vasodilator responses to acetylcholine and adenosine after reperfusion, but also reduced infarct size (P<0.01). Intramyocardial bleeding, which should reflect microvascular damage, was not found in dogs with SM-20550 treatment. Infarct size was correlated inversely with collateral blood flow in control (both, P<0.01) but not in SM-20550-treated animals. Furthermore, SM-20550 significantly suppressed ventricular fibrillation during both ischemia and reperfusion. These results suggest that protective effects of Na⁺–H⁺ exchange inhibitors on reperfused myocardium are due at least in part to microvascular protection.