Cardioprotective effect of mexiletine in acute myocardial ischemia tudies in the rabbit closed chest ischemia mode.
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 x kg(-1) h(-1)); and (3) Mex+Gli (n=8), pre-administration of glibenclamide (Gli; 0.5mg/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.
Inuo
Kimiatsu
K
Department of Internal Medicine, Kitasato University School of Medicine, Sagamihara, Japan. dogtail@med.kitasato-u.ac.jp
Niwano
Shinichi
S
Morohoshi
Yasuo
Y
Nakayama
Shigenobu
S
Ikeda
Kazuko
K
Kojima
Jisyou
J
Saito
Junko
J
Masuda
Takashi
T
Izumi
Tohru
T
D000208:Acute Disease; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000627:therapeutic use*; D002316:Cardiotonic Agents / Q000627:therapeutic use*; D017023:Coronary Angiography; D003331:Coronary Vessels / Q000187:drug effects / Q000503:physiopathology; D004195:Disease Models, Animal; D015640:Ion Channel Gating / Q000187:drug effects; D008565:Membrane Proteins / Q000187:drug effects / Q000502:physiology*; D008801:Mexiletine / Q000627:therapeutic use*; D017202:Myocardial Ischemia / Q000000981:diagnostic imaging / Q000503:physiopathology / Q000517:prevention & control*; D015221:Potassium Channels; D011817:Rabbits; D013997:Time Factors; D016277:Ventricular Function, Left / Q000187:drug effects / Q000502:physiology
D000889:Anti-Arrhythmia Agents; D002316:Cardiotonic Agents; D008565:Membrane Proteins; D015221:Potassium Channels; C117780:mitochondrial K(ATP) channel; D008801:Mexiletine