Cardioprotective effects of sarcolemmal and mitochondrial K-ATP channel openers in an experimental model of autoimmune myocarditis. Role of the reduction in calcium overload during acute heart failure.
Cardioprotective effects of sarcolemmal and mitochondrial K-ATP channel openers in an experimental model of autoimmune myocarditis. Role of the reduction in calcium overload during acute heart failure.
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DOI：
10.1536/ihj.53.139
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发表时间：
2012
影响因子：
1.5
通讯作者：
S. Niwano;Shoji Hirasawa;H. Niwano;Sae Sasaki;Ray Masuda;Kiyotaka Sato;T. Masuda;T. Izumi
中科院分区：
文献类型：
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作者：
S. Niwano;Shoji Hirasawa;H. Niwano;Sae Sasaki;Ray Masuda;Kiyotaka Sato;T. Masuda;T. Izumi
据报道，K-ATP 通道开放剂作为药理学预处理作用，在急性缺血中具有心脏保护作用。在本研究中，在实验性自身免疫性心肌炎（EAM）大鼠模型中评估了临床K-ATP通道开放剂，即尼可地尔（Nic）和美西律（Mex）对心功能的慢性影响。给EAM大鼠施用尼可地尔（3或10mg/kg/天）或Mex（10或25mg/kg/天），并在第21天（急性期）或第60天（慢性期）与未治疗的EAM大鼠（对照EAM）和没有EAM的假手术大鼠的效果进行比较。在急性期，对照 EAM 大鼠表现出左心室射血分数 (LVEF) 降低和单相动作电位持续时间 (MAPD) 延长。这两种药物对 LVEF 或心肌炎程度均没有影响，但 Mex 25 mg 抑制了 MAPD 延长。在慢性期，EAM+Nic 和 EAM+Mex 25 mg 表现出比对照 EAM 更高的 LVEF。尽管对照 EAM 表现出持续的 MAPD 延长，但其他组在慢性期表现出 MAPD 的恢复。对照EAM中的线粒体氧化还原状态低于假手术，并且EAM+Nic在慢性期表现出与假手术相似的氧化还原状态水平。尼可地尔通过保护线粒体功能表现出心脏保护作用。美西律可能通过缩短急性期的 MAPD 来减少钙超载，从而表现出心脏保护作用。
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.