title: Systemic and mesenteric O2 metabolism in endotoxic pigs: effect of ibuprofen and meclofenamate.
abstract: The effect of two chemically dissimilar cyclooxygenase inhibitors was studied in pentobarbital-anesthetized endotoxic pigs. Animals in groups II-IV were infused with Escherichia coli lipopolysaccharide (LPS, 150 micrograms/kg) and resuscitated with normal saline (1.2 ml.kg-1.min-1). Animals in group I (n = 4) were resuscitated as above but were not infused with LPS. Animals in group II (n = 7) served as endotoxic controls. Pigs in groups III (n = 6) and IV (n = 5) were pre- and posttreated with ibuprofen (10 mg/kg bolus then 10 mg.kg-1.h-1 and meclofenamate (5 mg/kg then 5 mg.kg-1.h-1, respectively. Ileal intramucosal hydrogen ion concentration [( H+]) was estimated tonometrically. In group I, cardiac index (CI), mean arterial pressure (MAP), superior mesenteric arterial perfusion (QSMA), and mesenteric O2 delivery (DO2) increased significantly, but other variables were unchanged. After infusion of LPS in group II, MAP and systemic vascular resistance index were markedly diminished but CI was well preserved. In this group, QSMA, systemic DO2, and mesenteric DO2 decreased, whereas systemic O2 uptake (VO2) and gut [H+] increased; mesenteric VO2 was unchanged. Compared with pigs in group II, pigs treated with ibuprofen or meclofenamate manifested improved systemic and mesenteric DO2. In groups III and IV, QSMA remained normal, increased systemic VO2 was not observed, and gut intramucosal acidosis was ameliorated. Increased intramucosal [H+] in group II suggests that QSMA was inadequate. The salutary effects of ibuprofen and meclofenamate suggest that inadequate mesenteric perfusion was mediated, at least in part, by cyclooxygenase-derived metabolites or arachidonic acid.
authors.affiliation: Department of Surgery, University of Massachusetts Medical Center, Worcester 01655.
authors.forename: M P
authors.initials: MP
authors.lastname: Fink
authors.forename: H R
authors.initials: HR
authors.lastname: Rothschild
authors.forename: Y F
authors.initials: YF
authors.lastname: Deniz
authors.forename: H L
authors.initials: HL
authors.lastname: Wang
authors.forename: P C
authors.initials: PC
authors.lastname: Lee
authors.forename: S M
authors.initials: SM
authors.lastname: Cohn
mesh_terms: D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood; D000704:Analysis of Variance; D000818:Animals; D016861:Cyclooxygenase Inhibitors; D004731:Endotoxins; D006439:Hemodynamics; D006863:Hydrogen-Ion Concentration; D007052:Ibuprofen / Q000494:pharmacology*; D008070:Lipopolysaccharides; D008297:Male; D008469:Meclofenamic Acid / Q000494:pharmacology*; D008643:Mesentery / Q000378:metabolism*; D010100:Oxygen / Q000097:blood / Q000378:metabolism*; D012772:Shock, Septic / Q000097:blood / Q000188:drug therapy / Q000378:metabolism*; D013552:Swine; D013929:Thromboxane B2 / Q000097:blood; D062367:ortho-Aminobenzoates / Q000494:pharmacology*
chemical_list: D016861:Cyclooxygenase Inhibitors; D004731:Endotoxins; D008070:Lipopolysaccharides; D062367:ortho-Aminobenzoates; D008469:Meclofenamic Acid; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; C044101:endotoxin, Escherichia coli; D010100:Oxygen; D007052:Ibuprofen