Abstract
INTRODUCTION: Infections produce severe respiratory muscle weakness, which contributes to the development of respiratory failure. An effective, safe therapy to prevent respiratory muscle dysfunction in infected patients has not been defined. This study examined the effect of eicosapentaenoic acid (EPA), an immunomodulator that can be safely administered to patients, on diaphragm force generation following endotoxin administration.
METHODS: Rats were administered the following (n = 5/group): (a) saline, (b) endotoxin, 12 mg/kg IP, (c) endotoxin + EPA (1.0 g/kg/d), and (d) EPA alone. Diaphragms were removed and measurements made of the diaphragm force-frequency curve, calpain activation, caspase activation, and protein carbonyl levels.
RESULTS: Endotoxin elicited large reductions in diaphragm specific force generation (P < 0.001), and increased diaphragm caspase activation (P < 0.01), calpain activation (P < 0.001) and protein carbonyl levels (P < 0.01). EPA administration attenuated endotoxin-induced reductions in diaphragm specific force, with maximum specific force levels of 27 +/- 1, 14 +/- 1, 23 +/- 1, and 24 +/- 1 N/cm2, respectively, for control, endotoxin, endotoxin + EPA, and EPA treated groups (P < 0.001). EPA did not prevent endotoxin induced caspase activation or protein carbonyl formation but significantly reduced calpain activation (P < 0.02).
CONCLUSIONS: These data indicate that endotoxin-induced reductions in diaphragm specific force generation can be partially prevented by administration of EPA, a nontoxic biopharmaceutical that can be safely given to patients. We speculate that it may be possible to reduce infection-induced skeletal muscle weakness in critically ill patients by administration of EPA.
Document Type
Article
Publication Date
3-16-2010
Digital Object Identifier (DOI)
http://dx.doi.org/10.1186/cc8913
Repository Citation
Supinski, Gerald S.; Vanags, Jonas; and Callahan, Leigh Ann, "Eicosapentaenoic acid preserves diaphragm force generation following endotoxin administration" (2010). Internal Medicine Faculty Publications. 22.
https://uknowledge.uky.edu/internalmedicine_facpub/22
Notes/Citation Information
Published in Critical Care, v. 14, R35.
© 2010 Supinski et al.; licensee BioMed Central Ltd.
This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.