Trolox Attenuates Mechanical Ventilation–induced Diaphragmatic Dysfunction and Proteolysis

ASU Author/Contributor (non-ASU co-authors, if there are any, appear on document)
Andrew Shanely Ph.D, Associate Professor (Creator)
Appalachian State University (ASU )
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Abstract: Prolonged mechanical ventilation results in diaphragmatic oxida-tive injury, elevated proteolysis, fiber atrophy, and reduced force-generating capacity. We tested the hypothesis that antioxidant infusion during mechanical ventilation would function as an antioxi-dant to maintain redox balance within diaphragm muscle fibers and therefore prevent oxidative stress and subsequent proteolysis and contractile dysfunction. Sprague-Dawley rats were anesthe-tized, tracheostomized, and mechanically ventilated with 21% O2 for 12 hours. The antioxidant Trolox was intravenously infused in a subset of ventilated animals. Compared with acutely anesthetized, nonventilated control animals, mechanical ventilation resulted in a significant reduction (–17%) in diaphragmatic maximal tetanic force. Importantly, Trolox completely attenuated this mechanical ventilation-induced diaphragmatic contractile deficit. Total dia-phragmatic proteolysis was increased 105% in mechanical ventila-tion animals compared with controls. In contrast, diaphragmatic proteolysis did not differ between controls and mechanical ventila-tion–Trolox animals. Moreover, 20S proteasome activity in the dia-phragm was elevated in the mechanical ventilation animals (+76%); Trolox treatment attenuated this mechanical ventilation-induced rise in protease activity. These results are consistent with the hypothesis that mechanical ventilation-induced oxidative stress is an important factor regulating mechanical ventilation-induced diaphragmatic proteolysis and contractile dysfunction. Our findings suggest that antioxidant therapy could be beneficial during pro-longed mechanical ventilation

Additional Information

Jenna L. Betters, David S. Criswell, R. Andrew Shanely, Darin Van Gammeren, Darin Falk, Keith C. DeRuisseau, Melissa Deering, Tossaporn Yimlamai, and Scott K. Powers (2004) "Trolox Attenuates Mechanical Ventilation–induced Diaphragmatic Dysfunction and Proteolysis" American Journal Of Respiratory And Critical Care Medicine Vol 170 Version of Record Available @ DOI: 10.1164/rccm.200407-939OC
Language: English
Date: 2004
antioxidant, protein degradation, rat, weaning

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