Sepsis-induced myopathy
- 1 October 2009
- journal article
- review article
- Published by Ovid Technologies (Wolters Kluwer Health) in Critical Care Medicine
- Vol. 37, S354-S367
- https://doi.org/10.1097/ccm.0b013e3181b6e439
Abstract
Sepsis is a major cause of morbidity and mortality in critically ill patients, and despite advances in management, mortality remains high. In survivors, sepsis increases the risk for the development of persistent acquired weakness syndromes affecting both the respiratory muscles and the limb muscles. This acquired weakness results in prolonged duration of mechanical ventilation, difficulty weaning, functional impairment, exercise limitation, and poor health-related quality of life. Abundant evidence indicates that sepsis induces a myopathy characterized by reductions in muscle force-generating capacity, atrophy (loss of muscle mass), and altered bioenergetics. Sepsis elicits derangements at multiple subcellular sites involved in excitation contraction coupling, such as decreasing membrane excitability, injuring sarcolemmal membranes, altering calcium homeostasis due to effects on the sarcoplasmic reticulum, and disrupting contractile protein interactions. Muscle wasting occurs later and results from increased proteolytic degradation as well as decreased protein synthesis. In addition, sepsis produces marked abnormalities in muscle mitochondrial functional capacity and when severe, these alterations correlate with increased death. The mechanisms leading to sepsis-induced changes in skeletal muscle are linked to excessive localized elaboration of proinflammatory cytokines, marked increases in free-radical generation, and activation of proteolytic pathways that are upstream of the proteasome including caspase and calpain. Emerging data suggest that targeted inhibition of these pathways may alter the evolution and progression of sepsis-induced myopathy and potentially reduce the occurrence of sepsis-mediated acquired weakness syndromes.Keywords
This publication has 138 references indexed in Scilit:
- Calpain-1 is required for hydrogen peroxide-induced myotube atrophyAmerican Journal of Physiology-Cell Physiology, 2009
- Neutrophil-induced skeletal muscle damage: a calculated and controlled response following hindlimb unloading and reloadingAmerican Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 2008
- Sarcolemma-localized nNOS is required to maintain activity after mild exerciseNature, 2008
- Calpain activity and muscle wasting in sepsisAmerican Journal of Physiology-Endocrinology and Metabolism, 2008
- Mechanisms of Neuromuscular Dysfunction in Critical IllnessCritical Care Clinics, 2008
- Novel aspects on the regulation of muscle wasting in sepsisThe International Journal of Biochemistry & Cell Biology, 2005
- Quality of life in adult survivors of critical illness: A systematic review of the literatureIntensive Care Medicine, 2005
- Role of ubiquitin-proteasome pathway in skeletal muscle wasting in rats with endotoxemiaCritical Care Medicine, 2003
- Multiple Classes of Sulfhydryls Modulate the Skeletal Muscle Ca2+ Release ChannelOnline Journal of Public Health Informatics, 1997
- Sepsis stimulates nonlysosomal, energy-dependent proteolysis and increases ubiquitin mRNA levels in rat skeletal muscle.JCI Insight, 1994