Pressure support ventilation attenuates ventilator-induced protein modifications in the diaphragm.
BACKGROUND
Controlled mechanical ventilation (CMV) induces profound modifications of diaphragm protein metabolism, including muscle atrophy and severe ventilator-induced diaphragmatic dysfunction. Diaphragmatic modifications could be decreased by spontaneous breathing. We hypothesized that mechanical ventilation in pressure support ventilation (PSV), which preserves diaphragm muscle activity, would limit diaphragmatic protein catabolism.


METHODS
Forty-two adult Sprague-Dawley rats were included in this prospective randomized animal study. After intraperitoneal anesthesia, animals were randomly assigned to the control group or to receive 6 or 18 hours of CMV or PSV. After sacrifice and incubation with 14C-phenylalanine, in vitro proteolysis and protein synthesis were measured on the costal region of the diaphragm. We also measured myofibrillar protein carbonyl levels and the activity of 20S proteasome and tripeptidylpeptidase II.


RESULTS
Compared with control animals, diaphragmatic protein catabolism was significantly increased after 18 hours of CMV (33%, P = 0.0001) but not after 6 hours. CMV also decreased protein synthesis by 50% (P = 0.0012) after 6 hours and by 65% (P < 0.0001) after 18 hours of mechanical ventilation. Both 20S proteasome activity levels were increased by CMV. Compared with CMV, 6 and 18 hours of PSV showed no significant increase in proteolysis. PSV did not significantly increase protein synthesis versus controls. Both CMV and PSV increased protein carbonyl levels after 18 hours of mechanical ventilation from +63% (P < 0.001) and +82% (P < 0.0005), respectively.


CONCLUSIONS
PSV is efficient at reducing mechanical ventilation-induced proteolysis and inhibition of protein synthesis without modifications in the level of oxidative injury compared with continuous mechanical ventilation. PSV could be an interesting alternative to limit ventilator-induced diaphragmatic dysfunction.
Futier
Emmanuel
E
General Intensive Care Unit, Hotel-Dieu Hospital, University Hospital of Clermont-Ferrand, Boulevard L. Malfreyt, Clermond-Ferrand, 63058, France.
Constantin
Jean-Michel
JM
Combaret
Lydie
L
Mosoni
Laurent
L
Roszyk
Laurence
L
Sapin
Vincent
V
Attaix
Didier
D
Jung
Boris
B
Jaber
Samir
S
Bazin
Jean-Etienne
JE
D000818:Animals; D003964:Diaphragm / Q000378:metabolism*; D009124:Muscle Proteins / Q000096:biosynthesis*; D011175:Positive-Pressure Respiration / Q000379:methods*; D011446:Prospective Studies; D014176:Protein Biosynthesis / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012121:Respiration, Artificial / Q000379:methods
D009124:Muscle Proteins
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