title: Blunted hypoxic vasoconstriction in oleic acid lung injury: effect of cyclooxygenase inhibitors.
abstract: Cyclooxygenase inhibitors have been reported to accentuate pulmonary hypertension and to improve gas exchange in oleic acid (OA) lung injury (Leeman et al. J. Appl. Physiol. 65: 662-668, 1988), suggesting inhibition of hypoxic pulmonary vasoconstriction by a vasodilating prostaglandin. To test this hypothesis, the hypoxic pulmonary vasoreactivity was examined at constant flow (Q; with an arteriovenous femoral bypass or a balloon catheter placed in the inferior vena cava) before and after OA in three groups of anesthetized and ventilated [inspired O2 fraction (FIO2) 0.4] dogs. Intrapulmonary shunt was measured using a SF6 infusion. A time control group (n = 7) had two consecutive hypoxic challenges after OA and received no drug. A treatment group (n = 6) received indomethacin (2 mg/kg iv) before the second hypoxic challenge after OA. A pretreatment group received indomethacin (2 mg/kg iv, n = 7) or aspirin (30 mg/kg iv, n = 6) before OA. In control and treated dogs, the hypoxic pulmonary vasopressor response was attenuated after OA. It was restored after indomethacin but also during the second hypoxic stimulus in the control dogs. After OA, gas exchange at FIO2 0.4 improved with indomethacin but not in controls. In pretreated dogs the hypoxic vasopressor response to hypoxia was preserved after OA, and gas exchange at FIO2 0.4 was less deteriorated compared with nonpretreated dogs (arterial O2 pressure 139 +/- 7 vs. 76 +/- 6 Torr, P less than 0.01, and intrapulmonary shunt 14 +/- 2 vs. 41 +/- 5%, P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Laboratory of Cardiovascular and Respiratory Physiology, Erasme University Hospital, Brussels, Belgium.
authors.forename: M
authors.initials: M
authors.lastname: Leeman
authors.forename: M
authors.initials: M
authors.lastname: Delcroix
authors.forename: J L
authors.initials: JL
authors.lastname: Vachiéry
authors.forename: C
authors.initials: C
authors.lastname: Mélot
authors.forename: R
authors.initials: R
authors.lastname: Naeije
mesh_terms: D000818:Animals; D001241:Aspirin / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004285:Dogs; D011464:Epoprostenol / Q000378:metabolism; D000860:Hypoxia / Q000503:physiopathology*; D007213:Indomethacin / Q000494:pharmacology; D008168:Lung / Q000187:drug effects / Q000503:physiopathology; D055370:Lung Injury; D019301:Oleic Acid; D009829:Oleic Acids; D011652:Pulmonary Circulation / Q000187:drug effects / Q000502:physiology*; D011654:Pulmonary Edema / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control; D011659:Pulmonary Gas Exchange / Q000187:drug effects / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*
chemical_list: D016861:Cyclooxygenase Inhibitors; D009829:Oleic Acids; D019301:Oleic Acid; D011464:Epoprostenol; D001241:Aspirin; D007213:Indomethacin