Systemic and mesenteric O₂ metabolism in endotoxic pigs: Effect of ibuprofen and meclofenamate

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 μg/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 (Q̇SMA), and mesenteric O₂ delivery (ḊO₂) 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, Q̇SMA, systemic ḊO₂, and mesenteric ḊO₂ decreased, whereas systemic O₂ uptake (V̇O₂) and gut [H⁺] increased; mesenteric V̇O₂ was unchanged. Compared with pigs in group II, pigs treated with ibuprofen or meclofenamate manifested improved systemic and mesenteric ḊO₂. In groups III and IV, Q̇SMA remained normal, increased systemic V̇O₂ was not observed, and gut intramucosal acidosis was ameliorated. Increased intramucosal [H⁺] in group II suggests that Q̇SMA 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.