title: Pressure support ventilation attenuates ventilator-induced protein modifications in the diaphragm.
abstract: 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.
authors.affiliation: General Intensive Care Unit, Hotel-Dieu Hospital, University Hospital of Clermont-Ferrand, Boulevard L. Malfreyt, Clermond-Ferrand, 63058, France.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Futier
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Constantin
authors.forename: Lydie
authors.initials: L
authors.lastname: Combaret
authors.forename: Laurent
authors.initials: L
authors.lastname: Mosoni
authors.forename: Laurence
authors.initials: L
authors.lastname: Roszyk
authors.forename: Vincent
authors.initials: V
authors.lastname: Sapin
authors.forename: Didier
authors.initials: D
authors.lastname: Attaix
authors.forename: Boris
authors.initials: B
authors.lastname: Jung
authors.forename: Samir
authors.initials: S
authors.lastname: Jaber
authors.forename: Jean-Etienne
authors.initials: JE
authors.lastname: Bazin
mesh_terms: 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
chemical_list: D009124:Muscle Proteins
references.citation: Am J Respir Crit Care Med. 2004 Sep 15;170(6):626-32
references.pmid: 15201132
references.citation: Curr Opin Clin Nutr Metab Care. 2001 Jan;4(1):45-9
references.pmid: 11122559
references.citation: Chest. 2003 Jan;123(1):195-201
references.pmid: 12527622
references.citation: Am J Physiol Cell Physiol. 2004 Oct;287(4):C834-43
references.pmid: 15355854
references.citation: Am Rev Respir Dis. 1987 Aug;136(2):411-5
references.pmid: 3619200
references.citation: Am J Respir Crit Care Med. 2002 Nov 15;166(10):1369-74
references.pmid: 12421745
references.citation: Anesthesiology. 1974 Sep;41(3):242-55
references.pmid: 4604401
references.citation: Am J Physiol Cell Physiol. 2003 Oct;285(4):C806-12
references.pmid: 12773310
references.citation: Int J Biochem Cell Biol. 1999 Jul;31(7):751-7
references.pmid: 10467731
references.citation: Am J Respir Crit Care Med. 2004 Feb 1;169(3):336-41
references.pmid: 14739134
references.citation: Clin Sci (Lond). 2000 Sep;99(3):181-7
references.pmid: 11787469
references.citation: Exerc Sport Sci Rev. 2002 Apr;30(2):69-74
references.pmid: 11991540
references.citation: Am Rev Respir Dis. 1989 Feb;139(2):513-21
references.pmid: 2643905
references.citation: N Engl J Med. 2008 Mar 27;358(13):1327-35
references.pmid: 18367735
references.citation: J Appl Physiol (1985). 1985 Mar;58(3):823-9
references.pmid: 3920194
references.citation: J Appl Physiol (1985). 2003 Sep;95(3):1116-24
references.pmid: 12777408
references.citation: J Appl Physiol Respir Environ Exerc Physiol. 1984 Mar;56(3):753-64
references.pmid: 6706781
references.citation: Vet Ther. 2002 Fall;3(3):215-25
references.pmid: 12447828
references.citation: Crit Care. 2006 Feb;10(1):102
references.pmid: 16420654
references.citation: Crit Care. 2006 Feb;10(1):204
references.pmid: 16356210
references.citation: Am J Respir Crit Care Med. 2004 Dec 1;170(11):1179-84
references.pmid: 15374845
references.citation: Intensive Care Med. 2008 Mar;34(3):523-7
references.pmid: 18087691
references.citation: Am J Physiol. 1995 Jun;268(6 Pt 1):C1369-74
references.pmid: 7611354
references.citation: Am J Physiol. 1993 Dec;265(6 Pt 1):E839-44
references.pmid: 8279538
references.citation: Biochem Biophys Res Commun. 1997 Feb 3;231(1):37-41
references.pmid: 9070215
references.citation: Intensive Care Med. 2005 Oct;31(10):1427-33
references.pmid: 16041522
references.citation: Biochem Biophys Res Commun. 2002 Aug 9;296(1):41-7
references.pmid: 12147224
references.citation: Proc Nutr Soc. 2004 May;63(2):357-61
references.pmid: 15294055
references.citation: Intensive Care Med. 1993;19 Suppl 2:S69-73
references.pmid: 8106681
references.citation: Am J Respir Crit Care Med. 2005 Nov 15;172(10):1267-75
references.pmid: 16126937
references.citation: Journ Annu Diabetol Hotel Dieu. 2002;:93-103
references.pmid: 12525134
references.citation: J Appl Physiol Respir Environ Exerc Physiol. 1983 Jun;54(6):1635-40
references.pmid: 6874487
references.citation: Clin Sci (Lond). 1989 Dec;77(6):651-5
references.pmid: 2514062
references.citation: J Appl Physiol (1985). 2001 Oct;91(4):1669-78
references.pmid: 11568149
references.citation: Am J Respir Crit Care Med. 1994 Jun;149(6):1539-44
references.pmid: 8004310
references.citation: Am J Respir Crit Care Med. 2002 Oct 15;166(8):1135-40
references.pmid: 12379560
references.citation: J Anat. 1976 Nov;122(Pt 2):455-465
references.pmid: 1002614
references.citation: Can J Anaesth. 2004 May;51(5):494-9
references.pmid: 15128638
references.citation: Biochem J. 1997 May 15;324 ( Pt 1):1-18
references.pmid: 9164834
references.citation: J Appl Physiol (1985). 2002 Jun;92(6):2585-95
references.pmid: 12015377
references.citation: Am J Respir Crit Care Med. 2007 Jan 15;175(2):150-9
references.pmid: 17082496
references.citation: Arch Biochem Biophys. 1988 May 15;263(1):137-49
references.pmid: 3369859
references.citation: J Lab Clin Med. 1957 Nov;50(5):733-6
references.pmid: 13476030
references.citation: Biochem J. 2002 Jan 15;361(Pt 2):185-92
references.pmid: 11772390
references.citation: Anal Biochem. 1985 Oct;150(1):76-85
references.pmid: 3843705
references.citation: Science. 2001 Nov 23;294(5547):1704-8
references.pmid: 11679633
references.citation: Cancer Res. 1994 Nov 1;54(21):5568-73
references.pmid: 7923198
references.citation: Am J Physiol. 1999 Aug;277(2):R434-40
references.pmid: 10444550
references.citation: Am J Respir Crit Care Med. 2004 Nov 1;170(9):994-9
references.pmid: 15297271
references.citation: Crit Care. 2006;10(6):236
references.pmid: 17096868
references.citation: Am J Respir Crit Care Med. 2002 Nov 15;166(10):1307-8
references.pmid: 12421738
references.citation: J Biol Chem. 1982 Feb 25;257(4):1613-21
references.pmid: 6915936
references.citation: Intensive Care Med. 2008 Jan;34(1):7-16
references.pmid: 17928995
references.citation: Am J Respir Crit Care Med. 2007 Jun 1;175(11):1134-8
references.pmid: 17379854
references.citation: Am J Physiol. 1992 Mar;262(3 Pt 1):E253-60
references.pmid: 1550218
references.citation: J Biol Chem. 1951 Nov;193(1):265-75
references.pmid: 14907713
references.citation: Crit Care Med. 2005 Dec;33(12):2804-9
references.pmid: 16352963
references.citation: Am J Respir Crit Care Med. 2002 Oct 15;166(8):1017-8
references.pmid: 12379541