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Sepsis-Induced Myocardial Dysfunction (SIMD): the Pathophysiological Mechanisms and Therapeutic Strategies Targeting Mitochondria

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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… Click to show full abstract

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.

Keywords: sepsis; myocardial dysfunction; dysfunction simd; dysfunction; induced myocardial; sepsis induced

Journal Title: Inflammation
Year Published: 2020

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