NHE1-inhibitor cariporide prevents the transient reperfusion-induced shortening of the monophasic action potential after coronary ischemia in pigs

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• 作者：Klaus J. Wirth ; Thomas Maier and Andreas E. Busch
• 关键词：Key words Na+ ; H+ ; exchanger &#8211 ; ischemia/reperfusion &#8211 ; monophasic action potential duration &#8211 ; ventricular arrhythmias &#8211 ; pigs
• 刊名：Basic Research in Cardiology
• 出版年：2001
• 出版时间：March 2001
• 年：2001
• 卷：96
• 期：2
• 页码：192-197
• 全文大小：171 KB

文摘

During myocardial ischemia intracellular acid load increases as a consequence of anaerobic metabolism. Exchange of excessive protons for sodium via the sodium proton exchanger type 1 (NHE1) is supposed to cause intracellular sodium accumulation. The NHE1 inhibitor cariporide has been shown to inhibit ischemia and reperfusion-induced ventricular fibrillation (VF) but the mechanisms are not fully understood. During early reperfusion transient shortening of the action potential has been reported, which renders the heart susceptible to reentrant arrhythmias. In anesthetized pigs subjected to 10 min of left circumflex coronary artery (LCX) occlusion and reperfusion we have investigated whether NHE1 is involved in reperfusion-induced shortening of the monophasic action potential (MAP) taken with an epicardial probe over the ischemic area. In control pigs (n = 7) a moderate decrease in the duration of the MAP at 50 % repolarization (MAPD₅₀) occurred during ischemia reaching 78.8 ¡À 5.0 % of the pre-ischemic duration at 5 min (p < 0.01) and 87.3 ¡À 7.6 % after 10 min. An additional, transient but marked shortening occurred during the first 2 min of reperfusion, which fully recovered after 4 min. At 50 sec of reperfusion MAPD₅₀ fell to 53.1 ¡À 8.2 % of the pre-ischemic value corresponding to 90.1 ¡À 20.2 msec of reperfusion-induced shortening. Cariporide, 3 mg/kg i. v. 5 min before occlusion (n = 6), totally prevented reperfusion-induced MAP shortening while heaving no effect on MAPD₅₀ during ischemia.