title: Omega-3 polyunsaturated fatty acids delay the progression of endotoxic shock-induced myocardial dysfunction.
abstract: Septic shock has a high mortality rate, partially related to myocardial dysfunction. Polyunsaturated fatty acids (omega-3 PUFAs) possess anti-inflammatory and antioxidant properties, but whether omega-3 PUFAs exert beneficial effects on myocardial function is unknown. We investigated, in a rat model of endotoxic shock, the effects of omega-3 PUFAs pretreatment on cardiac hemodynamics, function, and oxidative stress as well as intestinal barrier. Endotoxic shock was induced by lipopolysaccharide (LPS; 20 mg/kg IP) administered to rats pretreated or not with omega-3 PUFAs (Omegaven®; 0.5 g/kg IP, 90 min before injection of LPS). Two or 5 h after LPS, left ventricular function and arterial pressure were measured, followed by assessment left ventricular total glutathione as well as tumor necrosis factor alpha expression, occuldin expression, and proteasome activities. LPS reduced mean arterial blood pressure to the same extent 2 and 5 h after its administration, but cardiac output was more markedly decreased after 5 h. Omega-3 PUFAs pretreatment did not significantly modify the effect of LPS on mean arterial pressure and total peripheral resistance, but prevented the decrease in cardiac output 2 h after LPS. LPS increased oxidized glutathione after 2 h, and this increase was significantly attenuated by omega-3 PUFAs. Simultaneously, omega-3 PUFAs increased myocardial hemeoxygenase-1 (HO-1) mRNA expression. Finally, omega-3 PUFAs prevented the reduction of intestinal occludin expression. Omega-3 PUFAs pre-treatment improves myocardial dysfunction during endotoxemia and increases myocardial HO-1 expression. Moreover, the preservation of the intestinal occludin induced by omega-3 PUFAs precedes myocardial protection, suggesting the involvement of the intestinal barrier in the myocardial improvement observed with omega-3 PUFAs parenteral supplementation.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale U1096, Rouen, France.
authors.forename: David
authors.initials: D
authors.lastname: Coquerel
authors.forename: Eva
authors.initials: E
authors.lastname: Kušíková
authors.forename: Paul
authors.initials: P
authors.lastname: Mulder
authors.forename: Moïse
authors.initials: M
authors.lastname: Coëffier
authors.forename: Sylvanie
authors.initials: S
authors.lastname: Renet
authors.forename: Pierre
authors.initials: P
authors.lastname: Dechelotte
authors.forename: Vincent
authors.initials: V
authors.lastname: Richard
authors.forename: Christian
authors.initials: C
authors.lastname: Thuillez
authors.forename: Fabienne
authors.initials: F
authors.lastname: Tamion
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D062186:Arterial Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D009202:Cardiomyopathies / Q000139:chemically induced / Q000188:drug therapy*; D004195:Disease Models, Animal; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology*; D005978:Glutathione / Q000032:analysis; D051547:Heme Oxygenase-1 / Q000096:biosynthesis / Q000235:genetics; D006439:Hemodynamics / Q000187:drug effects*; D008070:Lipopolysaccharides; D062793:Occludin / Q000096:biosynthesis; D018384:Oxidative Stress / Q000187:drug effects; D046988:Proteasome Endopeptidase Complex / Q000187:drug effects; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D012772:Shock, Septic / Q000188:drug therapy*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D016277:Ventricular Function, Left / Q000187:drug effects
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D015525:Fatty Acids, Omega-3; D008070:Lipopolysaccharides; D062793:Occludin; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D051547:Heme Oxygenase-1; D046988:Proteasome Endopeptidase Complex; D005978:Glutathione
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