Cardioprotective Effects of Sarcolemmal and Mitochondrial K-ATP Channel Openers in an Experimental Model of Autoimmune Myocarditis
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概要
- 論文の詳細を見る
It has been reported that K-ATP channel openers have a cardioprotective effect in acute ischemia as a pharmacological preconditioning effect. In the present study, the chronic effects of clinical K-ATP channel openers, ie, nicorandil (Nic) and mexiletine (Mex), on cardiac function were evaluated in a rat model of experimental autoimmune myocarditis (EAM). Nicorandil (3 or 10 mg/kg/day) or Mex (10 or 25 mg/kg/day) was administered to the EAM rats, and the effects were compared with those in untreated EAM rats (control EAM) and sham rats without EAM on day 21 (acute phase) or day 60 (chronic phase). In the acute phase, the control EAM rats exhibited a reduced left ventricular ejection fraction (LVEF) and prolonged monophasic action potential duration (MAPD). Neither drug had an affect on the LVEF or degree of myocarditis, but Mex 25 mg suppressed the MAPD prolongation. In the chronic phase, EAM+Nic and EAM+Mex 25 mg exhibited a higher LVEF than the control EAM. Although the control EAM exhibited sustained MAPD prolongation, the other groups showed recovery of the MAPD in the chronic phase. The mitochondorial redox state was lower in the control EAM than in the sham, and EAM+Nic exhibited a similar level of the redox state as the sham in the chronic phase. Nicorandil exhibited a cardioprotective effect through the protection of mitochondrial function. Mexiletine exhibited a cardioprotective effect possibly through a reduction in the calcium overload by shortening the MAPD in the acute phase.
著者
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Niwano Hiroe
Department Of Cardio-angiology Kitasato University School Of Medicine
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Sasaki Sae
Department of Cardio-angiology, Kitasato University School of Medicine
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Hirasawa Shoji
Department of Angio-Cardiology, Kitasato University School of Medicine
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Sasaki Sae
Department Of Cardio-angiology Kitasato University School Of Medicine
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Masuda Takashi
Departmant Of Emergency & Critical Care Medicine Kitasato University School Of Medicine
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Izumi Tohru
Department Of Angio-cardiology Kitasato University School Of Medicine
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Sato Kiyotaka
Department of Food Technology and Chemistry, Faculty of Fisheries and Animal Husbandry, Hiroshima University
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Niwano Shinichi
Department of Angio-Cardiology, Kitasato University School of Medicine
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Masuda Ray
Health Control Center, Chuo University
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Sasaki Sae
Department of Angio-Cardiology, Kitasato University School of Medicine
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