Research
Pressure support ventilation attenuates ventilator-induced protein modifications in the diaphragm
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* Corresponding author: Jean-Michel Constantin jmconstantin@chu-clermontferrand.fr
1 General Intensive Care Unit, Hotel-Dieu Hospital, University Hospital of Clermont-Ferrand, Boulevard L. Malfreyt, Clermond-Ferrand, 63058, France
2 Human Nutrition Research Center of Clermont-Ferrand, Nutrition and Protein Metabolism Unit, Institut National de la Recherche Agronomique, Route de Theix, Ceyrat, 63122 France
3 Department of Biochemistry, University Hospital of Clermont-Ferrand, Boulevard L. Malfreyt, Clermont-Ferrand, 63000, France
4 SAR B, Saint-Eloi Hospital, University Hospital of Montpellier, Avenue Augustin Fliche, Montpellier, 34000, France
Critical Care 2008, 12:R116 doi:10.1186/cc7010
Published: 11 September 2008Abstract
Introduction
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.