Circulation Journal
Online ISSN : 1347-4820
Print ISSN : 1346-9843
ISSN-L : 1346-9843
Experimental Investigation
Cardioprotective Effect of Mexiletine in Acute Myocardial Ischemia
Studies in the Rabbit Closed Chest Ischemia Model
Kimiatsu InuoShinichi NiwanoYasuo MorohoshiShigenobu NakayamaKazuko IkedaJisyou KojimaJunko SaitoTakashi MasudaTohru Izumi
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2002 Volume 66 Issue 4 Pages 403-410

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Abstract

ATP-sensitive K+ (KATP) channel openers have a cardioprotective effect and so mexiletine (Mex), a class Ib anti-arrhythmic drug, may also be cardioprotective because of its KATP channel-opening effect. The present study examined the effect of Mex on acute myocardial ischemia in a closed-chest acute ischemia and reperfusion model in rabbits. The rabbits were divided into 3 groups: (1) control (n=8); (2) Mex (n=8), continuous infusion of mexiletine (24 mg · kg -1 · h-1); and (3) Mex + Gli (n=8), pre-administration of glibenclamide (Gli; 0.5 mg/kg) followed by mexiletine infusion. The incidence of arrhythmia, the hemodynamics and left ventricular ejection fraction (LVEF), and the infarct size were evaluated and compared among the 3 groups. The incidence of fatal ventricular fibrillation (VF) was least in the Mex group. The LVEF at 30 min after reperfusion was least in the Mex group, but at 360 min after reperfusion, it was least in the Mex + Gli group. The area of myocardial infarction determined by 2,3-triphenyltetrazolium chloride (TTC) staining was smallest in the Mex group. In this model, Mex reduced infarct size and improved left ventricular function during the late phase after reperfusion, although the effect was totally negated by the addition of glibenclamide. (Circ J 2002; 66: 403 - 410)

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© 2002 THE JAPANESE CIRCULATION SOCIETY
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