Mechanical ventilation induces diaphragmatic mitochondrial dysfunction and increased oxidant production

Andreas N. Kavazis; Erin E. Talbert; Ashley J. Smuder; Matthew B. Hudson; W. Bradley Nelson; Scott K. Powers

doi:10.1016/j.freeradbiomed.2009.01.002

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Mechanical ventilation induces diaphragmatic mitochondrial dysfunction and increased oxidant production

Journal article

Peer reviewed

Mechanical ventilation induces diaphragmatic mitochondrial dysfunction and increased oxidant production

Andreas N. Kavazis, Erin E. Talbert, Ashley J. Smuder, Matthew B. Hudson, W. Bradley Nelson and Scott K. Powers

Free radical biology & medicine, Vol.46(6), pp.842-850

03/15/2009

DOI: 10.1016/j.freeradbiomed.2009.01.002

PMCID: PMC2906125

PMID: 19185055

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https://www.ncbi.nlm.nih.gov/pmc/articles/2906125View

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Abstract

Mechanical ventilation (MV) is a life-saving intervention used in patients with acute respiratory failure. Unfortunately, prolonged MV results in diaphragmatic weakness, which is an important contributor to the failure to wean patients from MV. Our laboratory has previously shown that reactive oxygen species (ROS) play a critical role in mediating diaphragmatic weakness after MV. However, the pathways responsible for MV-induced diaphragmatic ROS production remain unknown. These experiments tested the hypothesis that prolonged MV results in an increase in mitochondrial ROS release, mitochondrial oxidative damage, and mitochondrial dysfunction. To test this hypothesis, adult (3-4 months of age) female Sprague-Dawley rats were assigned to either a control or a 12-h MV group. After treatment, diaphragms were removed and mitochondria were isolated for subsequent respiratory and biochemical measurements. Compared to control, prolonged MV resulted in a lower respiratory control ratio in diaphragmatic mitochondria. Furthermore, diaphragmatic mitochondria from MV animals released higher rates of ROS in both State 3 and State 4 respiration. Prolonged MV was also associated with diaphragmatic mitochondrial oxidative damage as indicated by increased lipid peroxidation and protein oxidation. Finally, our data also reveal that the activities of the electron transport chain complexes II, III, and IV are depressed in mitochondria isolated from diaphragms of MV animals. In conclusion, these results are consistent with the concept that diaphragmatic inactivity promotes an increase in mitochondrial ROS emission, mitochondrial oxidative damage, and mitochondrial respiratory dysfunction. (c) 2009 Elsevier Inc. All rights reserved.

Biochemistry & Molecular Biology

Endocrinology & Metabolism

Life Sciences & Biomedicine

Science & Technology

Details

Title: Subtitle: Mechanical ventilation induces diaphragmatic mitochondrial dysfunction and increased oxidant production
Creators: Andreas N. Kavazis - University of Florida
Erin E. Talbert - University of Florida
Ashley J. Smuder - University of Florida
Matthew B. Hudson - University of Florida
W. Bradley Nelson - University of Florida
Scott K. Powers - University of Florida
Resource Type: Journal article
Publication Details: Free radical biology & medicine, Vol.46(6), pp.842-850
DOI: 10.1016/j.freeradbiomed.2009.01.002
PMID: 19185055
PMCID: PMC2906125
NLM abbreviation: Free Radic Biol Med
ISSN: 0891-5849
eISSN: 1873-4596
Publisher: Elsevier
Number of pages: 9
Grant note: R01HL072789 / NATIONAL HEART, LUNG, AND BLOOD INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI) R01-HL-072789 / National Heart, Lung, and Blood Institute; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI)
Language: English
Date published: 03/15/2009
Academic Unit: Fraternal Order of Eagles Diabetes Research Center; Health, Sport, and Human Physiology ; Internal Medicine
Record Identifier: 9984259401302771

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