Department of Critical Care Medicine, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Department of Cardiology, Cardiovascular Key Laboratory of Zhejiang Province, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Inflammation. 2020 Aug;43(4):1184-1200. doi: 10.1007/s10753-020-01233-w.
Sepsis is a lethal syndrome with multiple organ failure caused by an inappropriate host response to infection. Cardiac dysfunction is one of the important complications of sepsis, termed sepsis-induced myocardial dysfunction (SIMD), which is characterized by systolic and diastolic dysfunction of both sides of the heart. Mechanisms that contribute to SIMD include an excessive inflammatory response, altered circulatory, microvascular status, nitric oxide (NO) synthesis impairment, endothelial dysfunction, disorders of calcium regulation, cardiac autophagy anomaly, autonomic nervous system dysregulation, metabolic reprogramming, and mitochondrial dysfunction. The role of mitochondrial dysfunction, which is characterized by structural abnormalities, increased oxidative stress, abnormal opening of the mitochondrial permeability transition pore (mPTP), mitochondrial uncoupling, and disordered quality control systems, has been gaining increasing attention as a central player in the pathophysiology of SIMD. The disruption of homeostasis within the organism induced by mitochondrial dysfunction may also be an important aspect of SIMD development. In addition, an emerging therapy strategy targeting mitochondria, namely, metabolic resuscitation, seems promising. The current review briefly introduces the mechanism of SIMD, highlights how mitochondrial dysfunction contributes to SIMD, and discusses the role of metabolic resuscitation in the treatment of SIMD.
脓毒症是一种致命的综合征，由宿主对感染的不当反应引起多器官衰竭。心功能障碍是脓毒症的重要并发症之一，称为脓毒症诱导的心肌功能障碍（SIMD），其特征是心脏两侧的收缩和舒张功能障碍。导致 SIMD 的机制包括过度的炎症反应、循环和微血管状态改变、一氧化氮（NO）合成受损、内皮功能障碍、钙调节紊乱、心脏自噬异常、自主神经系统失调、代谢重编程和线粒体功能障碍。线粒体功能障碍的作用越来越受到关注，其特征是结构异常、氧化应激增加、线粒体通透性转换孔（mPTP）异常开放、线粒体解偶联和质量控制系统紊乱，作为 SIMD 病理生理学的核心参与者。线粒体功能障碍引起的机体内平衡破坏也可能是 SIMD 发展的一个重要方面。此外，一种针对线粒体的新兴治疗策略，即代谢复苏，似乎很有前途。本综述简要介绍了 SIMD 的发病机制，强调了线粒体功能障碍如何导致 SIMD，并讨论了代谢复苏在治疗 SIMD 中的作用。
