Diaphragm Unloading via Controlled Mechanical Ventilation Alters the Gene Expression Profile

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 )
Web Site: https://library.appstate.edu/

Abstract: Rationale: Prolonged controlled mechanical ventilation results in diaphragmatic inactivity and promotes oxidative injury, atrophy, and contractile dysfunction in this important inspiratory muscle. However, the impact of controlled mechanical ventilation on global mRNA alterations in the diaphragm remains unknown. Objectives: In these experiments, we used an Affymetrix oligonucleo-tide array to identify the temporal changes in diaphragmatic gene expression during controlled mechanical ventilation in the rat. Methods: Adult Sprague-Dawley rats were assigned to either control or mechanical ventilation groups (n =5/group). Mechanically venti-lated animals were anesthetized, tracheostomized, and ventilated with room air for 6 or 18 h. Animals in the control group were acutely anesthetized but not exposed to mechanical ventilation. Measurements and Main Results: Compared with control diaphragms, microarray analysis identified 354 differentially expressed, unique gene products after 6 and 18 h of mechanical ventilation. In general, genes in the cell growth/cell maintenance, stress response, and nucleic acid metabolism categories showed predominant upregula-tion, whereas genes in the structural protein and energy metabo-lism categories were predominantly downregulated. Conclusions: We conclude that mechanical ventilation results in rapid changes in diaphragmatic gene expression, and subsequently, many of these changes may contribute to atrophy and muscle fiber remodeling associated with unloading this primary inspiratory mus-cle. Importantly, this study also provides new insights into why the diaphragm, after the onset of contractile inactivity, atrophies more rapidly than locomotor skeletal muscles and also highlights unique differences that exist between these muscles in the mRNA response to inactivity.

Additional Information

Keith C. DeRuisseau, R. Andrew Shanely, Nagabhavani Akunuri, Marc T. Hamilton, Darin Van Gammeren, A. Murat Zergeroglu, Michael McKenzie, and Scott K. Powers (2005) "Diaphragm Unloading via Controlled Mechanical Ventilation Alters the Gene Expression Profile" American Journal Of Respiratory And Critical Care Medicine Vol 172 Version of Record Available @ (DOI: 10.1164/rccm.200503-403OC)
Language: English
Date: 2005
gene expression, microarray, muscle atrophy, respiratory muscle, weaning from mechanical ventilation

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