Mechanical Ventilation–induced Diaphragmatic Atrophy Is Associated with Oxidative Injury and Increased Proteolytic Activity

ASU Author/Contributor (non-ASU co-authors, if there are any, appear on document)
Andrew Shanely Ph.D, Associate Professor (Creator)
Institution
Appalachian State University (ASU )
Web Site: https://library.appstate.edu/

Abstract: Prolonged mechanical ventilation (MV) results in reduced diaphrag-matic maximal force production and diaphragmatic atrophy. To investigate the mechanisms responsible for MV-induced diaphrag-matic atrophy, we tested the hypothesis that controlled MV results in oxidation of diaphragmatic proteins and increased diaphrag-matic proteolysis due to elevated protease activity. Further, we postulated that MV would result in atrophy of all diaphragmatic muscle fiber types. Mechanically ventilated animals were anesthe-tized, tracheostomized, and ventilated with 21% O2 for 18 hours. MV resulted in a decrease (p <0.05) in diaphragmatic myofibrillar protein and the cross-sectional area of all muscle fiber types (i.e., I, IIa, IId/x, and IIb). Further, MV promoted an increase (p <.05) in diaphragmatic protein degradation along with elevated (p <0.05) calpain and 20S proteasome activity. Finally, MV was also associated with a rise (p <.05) in both protein oxidation and lipid peroxidation. These data support the hypothesis that MV is associated with atrophy of all diaphragmatic fiber types, increased diaphragmatic protease activity, and augmented diaphragmatic ox-idative stress.

Additional Information

Publication
R. Andrew Shanely, Murat A. Zergeroglu, Shannon L. Lennon, Takao Sugiura, Tossaporn Yimlamai, Debbie Enns, Angelo Belcastro, and Scott K. Powers (2002) "Mechanical Ventilation–induced Diaphragmatic Atrophy Is Associated with Oxidative Injury and Increased Proteolytic Activity" Version of Record Available @ American Journal Of Respiratory And Critical Care Medicine Vol 166 Version of Record Available @ (DOI: 10.1164/rccm.200202-088OC)
Language: English
Date: 2002
Keywords
myosin heavy chain, oxidative stress, protein degradation, weaning

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