Shin Borami, Cowan Douglas B, Emani Sitaram M, Del Nido Pedro J, McCully James D
Department of Cardiac Surgery, Boston Children's Hospital, Boston, MA, USA.
Department of Anesthesiology, Division of Cardiac Anesthesia Research, Harvard Medical School, Boston Children's Hospital, Boston, MA, USA.
Adv Exp Med Biol. 2017;982:595-619. doi: 10.1007/978-3-319-55330-6_31.
Ischemic heart disease remains the leading cause of death worldwide. Mitochondria are the power plant of the cardiomyocyte, generating more than 95% of the cardiac ATP. Complex cellular responses to myocardial ischemia converge on mitochondrial malfunction which persists and increases after reperfusion, determining the extent of cellular viability and post-ischemic functional recovery. In a quest to ameliorate various points in pathways from mitochondrial damage to myocardial necrosis, exhaustive pharmacologic and genetic tools have targeted various mediators of ischemia and reperfusion injury and procedural techniques without applicable success. The new concept of replacing damaged mitochondria with healthy mitochondria at the onset of reperfusion by auto-transplantation is emerging not only as potential therapy of myocardial rescue, but as gateway to a deeper understanding of mitochondrial metabolism and function. In this chapter, we explore the mechanisms of mitochondrial dysfunction during ischemia and reperfusion, current developments in the methodology of mitochondrial transplantation, mechanisms of cardioprotection and their clinical implications.
缺血性心脏病仍然是全球主要的死亡原因。线粒体是心肌细胞的动力工厂，产生超过95%的心脏ATP。心肌缺血的复杂细胞反应集中在线粒体功能障碍上，这种功能障碍在再灌注后持续存在并加剧，决定了细胞存活的程度和缺血后功能恢复情况。为了改善从线粒体损伤到心肌坏死这一过程中的各个环节，人们使用了大量的药理学和遗传学工具来针对缺血再灌注损伤的各种介质及操作技术，但均未取得成功。通过自体移植在再灌注开始时用健康线粒体替代受损线粒体这一新概念，不仅作为心肌挽救的潜在治疗方法出现，而且成为深入理解线粒体代谢和功能的途径。在本章中，我们探讨了缺血和再灌注期间线粒体功能障碍的机制、线粒体移植方法的当前进展、心脏保护机制及其临床意义。
