{"title":"Ventilator-induced diaphragm dysfunction: phenomenology and mechanism(s) of pathogenesis.","authors":"Scott K Powers","doi":"10.1113/JP283860","DOIUrl":null,"url":null,"abstract":"<p><p>Mechanical ventilation (MV) is used to support ventilation and pulmonary gas exchange in patients during critical illness and surgery. Although MV is a life-saving intervention for patients in respiratory failure, an unintended side-effect of MV is the rapid development of diaphragmatic atrophy and contractile dysfunction. This MV-induced diaphragmatic weakness is labelled as 'ventilator-induced diaphragm dysfunction' (VIDD). VIDD is an important clinical problem because diaphragmatic weakness is a risk factor for the failure to wean patients from MV. Indeed, the inability to remove patients from ventilator support results in prolonged hospitalization and increased morbidity and mortality. The pathogenesis of VIDD has been extensively investigated, revealing that increased mitochondrial production of reactive oxygen species within diaphragm muscle fibres promotes a cascade of redox-regulated signalling events leading to both accelerated proteolysis and depressed protein synthesis. Together, these events promote the rapid development of diaphragmatic atrophy and contractile dysfunction. This review highlights the MV-induced changes in the structure/function of diaphragm muscle and discusses the cell-signalling mechanisms responsible for the pathogenesis of VIDD. This report concludes with a discussion of potential therapeutic opportunities to prevent VIDD and suggestions for future research in this exciting field.</p>","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":null,"pages":null},"PeriodicalIF":4.7000,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Physiology-London","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1113/JP283860","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
引用次数: 0
Abstract
Mechanical ventilation (MV) is used to support ventilation and pulmonary gas exchange in patients during critical illness and surgery. Although MV is a life-saving intervention for patients in respiratory failure, an unintended side-effect of MV is the rapid development of diaphragmatic atrophy and contractile dysfunction. This MV-induced diaphragmatic weakness is labelled as 'ventilator-induced diaphragm dysfunction' (VIDD). VIDD is an important clinical problem because diaphragmatic weakness is a risk factor for the failure to wean patients from MV. Indeed, the inability to remove patients from ventilator support results in prolonged hospitalization and increased morbidity and mortality. The pathogenesis of VIDD has been extensively investigated, revealing that increased mitochondrial production of reactive oxygen species within diaphragm muscle fibres promotes a cascade of redox-regulated signalling events leading to both accelerated proteolysis and depressed protein synthesis. Together, these events promote the rapid development of diaphragmatic atrophy and contractile dysfunction. This review highlights the MV-induced changes in the structure/function of diaphragm muscle and discusses the cell-signalling mechanisms responsible for the pathogenesis of VIDD. This report concludes with a discussion of potential therapeutic opportunities to prevent VIDD and suggestions for future research in this exciting field.
期刊介绍:
The Journal of Physiology publishes full-length original Research Papers and Techniques for Physiology, which are short papers aimed at disseminating new techniques for physiological research. Articles solicited by the Editorial Board include Perspectives, Symposium Reports and Topical Reviews, which highlight areas of special physiological interest. CrossTalk articles are short editorial-style invited articles framing a debate between experts in the field on controversial topics. Letters to the Editor and Journal Club articles are also published. All categories of papers are subjected to peer reivew.
The Journal of Physiology welcomes submitted research papers in all areas of physiology. Authors should present original work that illustrates new physiological principles or mechanisms. Papers on work at the molecular level, at the level of the cell membrane, single cells, tissues or organs and on systems physiology are all acceptable. Theoretical papers and papers that use computational models to further our understanding of physiological processes will be considered if based on experimentally derived data and if the hypothesis advanced is directly amenable to experimental testing. While emphasis is on human and mammalian physiology, work on lower vertebrate or invertebrate preparations may be suitable if it furthers the understanding of the functioning of other organisms including mammals.