Kang Y James
University of Louisville School of Medicine, Department of Medicine, 511 South Floyd Street, MDR 530, Louisville, KY 40202, USA.
Curr Opin Drug Discov Devel. 2003 Jan;6(1):110-6.
Interest in cardiotoxicity has dramatically increased during the past two years, leading to exciting progress in our understanding of the field. Both clinical and experimental animal studies have emphasized the role of cardiotoxicity in myocardial pathogenesis. Exploration of the cardiotoxicity of air pollution and highly active antiretroviral therapy (HAART) through experimental animal studies have led to mechanistic insights. Novel therapeutic approaches are also under development. Continued efforts to investigate the mechanisms of cardiotoxicity induced by well-known drugs and chemicals, such as Adriamycin, have also generated critical insights into cardiac response to toxicants. Recognition of the significance of cardiotoxicity in myocardial pathogenesis has resulted in the identification of many other drugs or chemicals, such as arsenic trioxide, whose cardiotoxicity is of major concern in clinical applications. Mitochondrial cardiomyopathy, along with control of myocardial cell death, has also become an extensively studied subject. Ionic transport across the inner membrane of mitochondria, especially the function of mitochondrial ATP-sensitive K+ channels and the Ca(2+)-activated K+ channels in myocardial protection against oxidative injury, has attracted a great deal of attention. Novel approaches, such as functional genomics, proteomics and metabonomics, should significantly improve our understanding of cardiotoxicity.
在过去两年中，人们对心脏毒性的关注度大幅提高，这使得我们对该领域的认识取得了令人兴奋的进展。临床和实验动物研究都强调了心脏毒性在心肌发病机制中的作用。通过实验动物研究对空气污染和高效抗逆转录病毒疗法（HAART）的心脏毒性进行探索，已带来了对其机制的深入了解。新型治疗方法也正在研发中。持续致力于研究诸如阿霉素等知名药物和化学物质所诱导的心脏毒性机制，也为心脏对毒物的反应提供了关键见解。认识到心脏毒性在心肌发病机制中的重要性，已促使人们识别出许多其他药物或化学物质，如三氧化二砷，其心脏毒性在临床应用中备受关注。线粒体心肌病以及对心肌细胞死亡的控制，也已成为广泛研究的课题。线粒体内膜上的离子转运，特别是线粒体ATP敏感性钾通道和钙激活钾通道在心肌抵御氧化损伤中的功能，已引起了广泛关注。诸如功能基因组学、蛋白质组学和代谢组学等新型方法，应能显著增进我们对心脏毒性的理解。
