title: Impact of endotoxin challenge in obese pigs.
abstract: Studies exploring the influence of obesity on septic shock remain limited and controversial. Pigs were chosen as a clinically relevant species, resembling to humans in various functions. We hypothesize obesity may impair porcine acute endotoxic shock. Four groups of five "Yucatan" minipigs were studied: lean and obese control groups, lean lipopolysaccharide (LPS) group receiving Escherichia coli endotoxin (LPS) and obese LPS group receiving the same endotoxin dose. We measured hemodynamic and oxygenation parameters, skin microvascular blood flow at rest and during reactive hyperemia, von Willebrand factor, tumor necrosis factor α, and interleukin 6. All measurements were performed at baseline and at 30, 60, 90, 150, and 300 min. Results were given as median with 25th to 75th interquartile range. Control groups remained stable during the study period. In LPS groups, administration of endotoxin resulted in a typical hypokinetic shock. In obese LPS group at 300 min, we observed a significant impairment of cardiac index (1.2 [1.06-1.45] vs. 1.7 [1.57-1.97] L/min per m, P = 0.008) compared with the lean LPS group; moreover, pulmonary hypertension (mean arterial pressure: 42 [39-47] vs. 32 [28-34] mmHg, P = 0.008), hypoxemia (partial pressure of oxygen: 216 [178-262] vs. 325 [285-414] mmHg, P = 0.02), and lactate levels (5.8 [4.2-6.8] vs. 3.9 [2.2-5.5] mmol/L, P = 0.04) were significantly higher compared with the lean LPS group. Throughout the study, rest flow and peak flow during reactive hyperemia were more decreased in the obese LPS group. Compared with the lean LPS group, tumor necrosis factor α levels at 60 min (269 [178-428] vs. 126 [105-166] ng/mL, P = 0.03) and interleukin 6 levels at 300 min (101 [61-142] vs. 52 [36-64] ng/mL, P = 0.03) were significantly higher in the obese LPS group. In our model of endotoxic shock, obese pigs developed a more severe hemodynamic failure with pronounced microcirculatory dysfunction and proinflammatory response.
authors.affiliation: *Inserm U859; †European Genomic Institute for Diabetes (EGID), FR 3508; ‡Univ Lille 2; §Pole de Réanimation CHRU; ∥Inserm UMR 1011; ¶IPL; and **Centre de Biologie Pathologie CHRU, F-59000 Lille, France.
authors.forename: Thibault
authors.initials: T
authors.lastname: Duburcq
authors.forename: Thomas
authors.initials: T
authors.lastname: Hubert
authors.forename: Pierre
authors.initials: P
authors.lastname: Saint-Léger
authors.forename: Jacques
authors.initials: J
authors.lastname: Mangalaboyi
authors.forename: Raphael
authors.initials: R
authors.lastname: Favory
authors.forename: Valery
authors.initials: V
authors.lastname: Gmyr
authors.forename: Laurence
authors.initials: L
authors.lastname: Quintane
authors.forename: Anne
authors.initials: A
authors.lastname: Tailleux
authors.forename: Bart
authors.initials: B
authors.lastname: Staels
authors.forename: Antoine
authors.initials: A
authors.lastname: Tournoys
authors.forename: François
authors.initials: F
authors.lastname: Pattou
authors.forename: Mercé
authors.initials: M
authors.lastname: Jourdain
mesh_terms: D000818:Animals; D004731:Endotoxins / Q000494:pharmacology*; D004926:Escherichia coli; D006439:Hemodynamics; D008070:Lipopolysaccharides; D008297:Male; D008833:Microcirculation; D009765:Obesity / Q000503:physiopathology*; D010100:Oxygen / Q000097:blood*; D012772:Shock, Septic / Q000503:physiopathology*; D013552:Swine; D013556:Swine, Miniature
chemical_list: D004731:Endotoxins; D008070:Lipopolysaccharides; C044101:endotoxin, Escherichia coli; D010100:Oxygen