title: Ibuprofen improves survival but does not ameliorate increased gut mucosal permeability in endotoxic pigs.
abstract: Intravenous lipopolysaccharide (LPS) decreases superior mesenteric arterial blood flow and increases ileal mucosal permeability in pigs. We tested the hypothesis that these phenomena can be ameliorated by pretreatment and posttreatment with ibuprofen. Pentobarbital-anesthetized immature swine were mechanically ventilated (fraction of inspired oxygen, 0.5) and infused with Ringer's lactate (RL) solution (0.8 mL/kg per minute). Animals in group RL (n = 10) received no other interventions. Animals in group RL + LPS (n = 15) were infused with LPS (50 micrograms/kg) from a time range equal to 0 through 60 minutes. Animals in group RL + LPS + ibuprofen (n = 10) were similarly infused with LPS, but in addition, they received ibuprofen (10 mg/kg at -30 minutes and 10 mg/kg per hour from -30 through 210 minutes). Intestinal permeability was assessed by measuring plasma-to-lumen clearances of two hydrophilic probes (chromium 51-labeled edetic acid monohydrate [EDTA] and urea) and by expressing the results as a clearance ratio (CEDTA/CUREA). Survival was 100%, 67%, and 100% in groups RL, RL + LPS, and RL + LPS + ibuprofen, respectively. Among survivors only, CEDTA/CUREA increased significantly over time in both endotoxic groups, but not in nonendotoxic controls. Treatment with ibuprofen transiently blocked LPS-induced mesenteric hypoperfusion. These data indicate that mediators other than cyclooxygenase-derived metabolites of arachidonic acid are responsible for the adverse effect of LPS on mesenteric permeability to hydrophilic solutes in this porcine model.
authors.affiliation: Department of Surgery, University of Massachusetts Medical Center, Worcester.
authors.forename: M P
authors.initials: MP
authors.lastname: Fink
authors.forename: K L
authors.initials: KL
authors.lastname: Kaups
authors.forename: H
authors.initials: H
authors.lastname: Wang
authors.forename: H R
authors.initials: HR
authors.lastname: Rothschild
mesh_terms: D000818:Animals; D006439:Hemodynamics / Q000187:drug effects; D006863:Hydrogen-Ion Concentration; D007052:Ibuprofen / Q000494:pharmacology*; D007082:Ileum / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism*; D008070:Lipopolysaccharides; D008297:Male; D010100:Oxygen / Q000097:blood; D010539:Permeability; D012772:Shock, Septic / Q000378:metabolism* / Q000503:physiopathology; D013552:Swine; D013929:Thromboxane B2 / Q000097:blood
chemical_list: D008070:Lipopolysaccharides; D013929:Thromboxane B2; D010100:Oxygen; D007052:Ibuprofen