help button home button
AJRCCM
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by LANONE, S.
Right arrow Articles by BOCZKOWSKI, J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by LANONE, S.
Right arrow Articles by BOCZKOWSKI, J.

Am. J. Respir. Crit. Care Med., Volume 162, Number 6, December 2000, 2308-2315

Muscular Contractile Failure in Septic Patients
Role of the Inducible Nitric Oxide Synthase Pathway

SOPHIE LANONE, ALEXANDRE MEBAZAA, CHRISTOPHE HEYMES, DOMINIQUE HENIN, JUAN JOSE PODEROSO, YVES PANIS, CHRISTINE ZEDDA, TIMOTHY BILLIAR, DIDIER PAYEN, MICHEL AUBIER, and JORGE BOCZKOWSKI

Institut National de la Santé et de la Recherche Médicale (INSERM) U408 and IFR 02, Faculté X. Bichat, Service d'Anatomie Pathologique, Hôpital Bichat; Département d'Anesthésie-Réanimation, Service de Chirurgie Générale and INSERM U 127, IFR Circulation, Hôpital Lariboisière, Paris, France; Laboratorio de Metabolismo del Oxigeno, Hospital de Clinicas, Universidad de Buenos Aires, Buenos Aires, Argentina; and Department of Surgery, Presbyterian University Hospital, Pittsburgh, Pennsylvania

Skeletal muscle failure is a frequent manifestation of sepsis that affects prognosis and rehabilitation by impairing respiration and ambulation. Animal studies have shown that the inducible NO synthase (NOS2) is expressed in skeletal muscles during sepsis, likely affecting muscular function, by promoting the formation of the strong oxidant peroxynitrite. In contrast, whether human skeletal muscle expresses a functional NOS2 in similar conditions is unknown. We studied NOS2 expression (mRNA and protein) and activity and its role in contractile function in samples from rectus abdominis muscle obtained during surgical procedure in 16 septic patients and in 21 controls. Peroxynitrite formation was detected by immunohistochemical detection of nitrotyrosine residues. The main results of this study are as follows: (1) A significant increase in NOS2 mRNA, protein, and activity was found in muscles from septic patients, the expression of NOS2 protein positively correlating with sepsis severity. (2) Contractile force was significantly lower in septic than in control muscles. This phenomenon was not reverted by muscle incubation ex vivo with the NOS inhibitor L-NMMA, indicating that NO was not involved in force reduction at the time of biopsy. (3) NOS2 expression in skeletal myocytes was strongly co-localized with nitrotyrosine, revealing muscular peroxynitrite generation during the septic process, before the muscle was biopsied. Exposure of control muscles to an amount of peroxynitrite similar to that generated in septic muscles during the septic process resulted in a nonreversible reduction in force generation. These results suggest that NOS2 could be involved in the decreased muscular force of septic patients via the local generation of peroxynitrite.




This article has been cited by other articles:


Home page
 Br J AnaesthHome page
R. Pirracchio, B. Cholley, S. De Hert, A. C. Solal, and A. Mebazaa
Diastolic heart failure in anaesthesia and critical care
Br. J. Anaesth., June 1, 2007; 98(6): 707 - 721.
[Abstract] [Full Text] [PDF]

Home page
 J. Appl. Physiol.Home page
G. S. Supinski and L. A. Callahan
Free radical-mediated skeletal muscle dysfunction in inflammatory conditions
J Appl Physiol, May 1, 2007; 102(5): 2056 - 2063.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
T. Vassilakopoulos, K. Govindaraju, D. Parthenis, D. H. Eidelman, Y. Watanabe, and S. N. A. Hussain
Nitric oxide production in the ventilatory muscles in response to acute resistive loading
Am J Physiol Lung Cell Mol Physiol, April 1, 2007; 292(4): L1013 - L1022.
[Abstract] [Full Text] [PDF]

Home page
 Anesth. Analg.Home page
B. Hauser, H. Bracht, M. Matejovic, P. Radermacher, and B. Venkatesh
Nitric Oxide Synthase Inhibition in Sepsis? Lessons Learned from Large-Animal Studies
Anesth. Analg., August 1, 2005; 101(2): 488 - 498.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Endocrinol. Metab.Home page
Y. C. Luiking, M. M. Hallemeesch, W. H. Lamers, and N. E. P. Deutz
NOS3 is involved in the increased protein and arginine metabolic response in muscle during early endotoxemia in mice
Am J Physiol Endocrinol Metab, June 1, 2005; 288(6): E1258 - E1264.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Cell Physiol.Home page
R. A. Frost, G. J. Nystrom, and C. H. Lang
Lipopolysaccharide stimulates nitric oxide synthase-2 expression in murine skeletal muscle and C2C12 myoblasts via Toll-like receptor-4 and c-Jun NH2-terminal kinase pathways
Am J Physiol Cell Physiol, December 1, 2004; 287(6): C1605 - C1615.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Microbiol. Rev.Home page
I. A. Clark, L. M. Alleva, A. C. Mills, and W. B. Cowden
Pathogenesis of Malaria and Clinically Similar Conditions
Clin. Microbiol. Rev., July 1, 2004; 17(3): 509 - 539.
[Abstract] [Full Text] [PDF]

Home page
 ThoraxHome page
A Agusti, M Morla, J Sauleda, C Saus, and X Busquets
NF-{kappa}B activation and iNOS upregulation in skeletal muscle of patients with COPD and low body weight
Thorax, June 1, 2004; 59(6): 483 - 487.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
F. Laghi and M. J. Tobin
Disorders of the Respiratory Muscles
Am. J. Respir. Crit. Care Med., July 1, 2003; 168(1): 10 - 48.
[Abstract] [Full Text] [PDF]

Home page
 Eur Respir JHome page
A.G.N. Agusti, A. Noguera, J. Sauleda, E. Sala, J. Pons, and X. Busquets
Systemic effects of chronic obstructive pulmonary disease
Eur. Respir. J., February 1, 2003; 21(2): 347 - 360.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Cell Mol. Bio.Home page
E. Barreiro, A. S. Comtois, J. Gea, V. E. Laubach, and S. N.A. Hussain
Protein Tyrosine Nitration in the Ventilatory Muscles . Role of Nitric Oxide Synthases
Am. J. Respir. Cell Mol. Biol., April 1, 2002; 26(4): 438 - 446.
[Abstract] [Full Text] [PDF]

Home page
 Cardiovasc ResHome page
V. Adams, B. Nehrhoff, U. Spate, A. Linke, P. C Schulze, A. Baur, S. Gielen, R. Hambrecht, and G. Schuler
Induction of iNOS expression in skeletal muscle by IL-1{beta} and NF{kappa}B activation: an in vitro and in vivo study
Cardiovasc Res, April 1, 2002; 54(1): 95 - 104.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
F. Laghi
Curing the Septic Diaphragm with the Ventilator
Am. J. Respir. Crit. Care Med., January 15, 2002; 165(2): 145 - 146.
[Full Text] [PDF]

Home page
 CirculationHome page
A. Mebazaa, G. W. De Keulenaer, X. Paqueron, L. J. Andries, P. Ratajczak, S. Lanone, C. Frelin, D. Longrois, D. Payen, D. L. Brutsaert, et al.
Activation of Cardiac Endothelium as a Compensatory Component in Endotoxin-Induced Cardiomyopathy: Role of Endothelin, Prostaglandins, and Nitric Oxide
Circulation, December 18, 2001; 104(25): 3137 - 3144.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
M. J. Tobin
Taxonomy of AJRCCM, a New Series, and a Medley of Metaphors
Am. J. Respir. Crit. Care Med., October 15, 2001; 164(8): 1333 - 1335.
[Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
M. J. TOBIN
Critical Care Medicine in AJRCCM 2000
Am. J. Respir. Crit. Care Med., October 15, 2001; 164(8): 1347 - 1361.
[Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Proc. Am. Thorac. Soc. Am. J. Respir. Cell Mol. Biol.
Copyright © 2000 American Thoracic Society 		  New Orleans Int'l Conf