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急性冠状动脉综合征和心肌缺血-再灌注损伤治疗中的新药物选择:左西孟旦的潜在作用

New pharmacologic options in the treatment of acute coronary syndromes and myocardial ischemia-reperfusion injury: potential role of levosimendan.

作者信息

Garcia-Gonzalez M J, Dominguez-Rodriguez A, Abreu-Gonzalez P

机构信息

Coronary Care Unit, Department of Cardiology, University Hospital of Canary Islands, Tenerife, Canary Islands, Spain.

出版信息

Minerva Cardioangiol. 2007 Oct;55(5):625-35.

Abstract

Modern and effective therapeutic possibilities have improved the management and outcomes in acute coronary syndromes and acute myocardial infarction. However, substantial morbidity and mortality still remain. Myocardial ischemia-reperfusion injury may contribute to additional damage to myocardial necrosis and apoptosis. Therefore, it has been focused on attention and field of therapeutic actions in the last years. The main mechanisms involved in the pathogenesis of ischemia-reperfusion injury are depressed energy metabolism, elevated oxidative damage, and altered calcium homeostasis. In experimental trials, a variety of drugs have proved effectiveness for the prevention and treatment of the ischemia-reperfusion injury. However, its efficacy, not always confirmed, has not yet been established in clinical practice. On the basis of the strong evidence linking potassium ATP dependent channels opening in the myocardium and its proved cardioprotective role during ischemia, these channels have been pointed out as possible and promising pharmacological targets in this setting. Some evidences suggest that the calcium sensitizing agent levosimendan may have of beneficial and exerts cardioprotective effects on myocardial ischemia and ischemia-reperfusion injury. Further investigation is warranted on this novel application of levosimendan.

摘要

现代有效的治疗方法改善了急性冠脉综合征和急性心肌梗死的管理及治疗效果。然而,仍存在大量的发病率和死亡率。心肌缺血再灌注损伤可能会导致心肌坏死和凋亡的额外损伤。因此,在过去几年中,它一直是治疗行动关注的焦点和领域。缺血再灌注损伤发病机制中涉及的主要机制是能量代谢降低、氧化损伤增加和钙稳态改变。在实验性试验中,多种药物已被证明对缺血再灌注损伤的预防和治疗有效。然而,其疗效在临床实践中尚未得到证实,且并非总是得到确认。基于心肌中依赖ATP的钾通道开放与缺血期间已证实的心脏保护作用之间的有力证据,这些通道已被指出是这种情况下可能且有前景的药理学靶点。一些证据表明,钙增敏剂左西孟旦可能有益,并对心肌缺血和缺血再灌注损伤发挥心脏保护作用。有必要对左西孟旦的这种新应用进行进一步研究。

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