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Diaphragm unloading via controlled mechanical ventilation alters the gene expression profile
Keith C DeRuisseau1, R Andrew Shanely, Nagabhavani Akunuri
1Department of Applied Physiology and Kinesiology, University of Florida, Room 25, Florida Gym, Gainesville, Florida 32611, USA. keithd@hhp.ufl.edu
American Journal of Respiratory and Critical Care Medicine
|August 30, 2005
Summary
Mechanical ventilation rapidly alters diaphragm gene expression, causing atrophy and remodeling. This study reveals key mRNA changes in the diaphragm due to inactivity, differing from other skeletal muscles.
Area of Science:
- Physiology
- Molecular Biology
- Respiratory Medicine
Background:
- Prolonged mechanical ventilation leads to diaphragm inactivity, oxidative injury, atrophy, and dysfunction.
- The impact of mechanical ventilation on diaphragm mRNA expression is not well understood.
Purpose of the Study:
- To investigate temporal changes in diaphragm gene expression during mechanical ventilation in rats.
- To identify specific mRNA alterations in the diaphragm due to controlled mechanical ventilation.
Main Methods:
- Adult Sprague-Dawley rats were subjected to controlled mechanical ventilation for 6 or 18 hours.
- Diaphragmatic gene expression was analyzed using Affymetrix oligonucleotide arrays.
- Control animals were anesthetized but not ventilated.
Main Results:
- Microarray analysis revealed 354 differentially expressed genes in ventilated diaphragms after 6 and 18 hours.
- Genes related to cell growth, stress response, and nucleic acid metabolism were upregulated.
- Genes involved in structural proteins and energy metabolism were downregulated.
Conclusions:
- Mechanical ventilation induces rapid diaphragm gene expression changes, contributing to atrophy and remodeling.
- These findings explain the diaphragm's rapid atrophy compared to locomotor muscles during inactivity.
- The study highlights unique mRNA responses in the diaphragm to inactivity.