Diaphragm unloading via controlled mechanical ventilation alters the gene expression profile.
BACKGROUND
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.


OBJECTIVE
In these experiments, we used an Affymetrix oligonucleotide 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 ventilated 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.


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 upregulation, whereas genes in the structural protein and energy metabolism 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 muscle. 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.
DeRuisseau
Keith C
KC
Department of Applied Physiology and Kinesiology, University of Florida, Room 25, Florida Gym, Gainesville, Florida 32611, USA. keithd@hhp.ufl.edu
Shanely
R Andrew
RA
Akunuri
Nagabhavani
N
Hamilton
Marc T
MT
Van Gammeren
Darin
D
Zergeroglu
A Murat
AM
McKenzie
Michael
M
Powers
Scott K
SK
D000818:Animals; D002118:Calcium / Q000378:metabolism; D003964:Diaphragm / Q000378:metabolism / Q000473:pathology / Q000502:physiology*; D004734:Energy Metabolism / Q000502:physiology; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D009119:Muscle Contraction / Q000502:physiology; D018482:Muscle, Skeletal / Q000502:physiology; D018384:Oxidative Stress / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012121:Respiration, Artificial; D014158:Transcription, Genetic
D002118:Calcium