Effects of oleic acid on pulmonary capillary leak and thromboxanes

The role of arachidonic acid metabolites in oleic acid-induced lung injury in anesthetized dogs was investigated. Oleic acid was administered as a bolus injection into the pulmonary artery in the following dose sequence: 0.05, 0.10, and 0.20 ml/kg at 30, 60, and 120 min, respectively, after either indomethacin (10 mg/kg iv) or vehicle. A control group (n = 3) received normal saline instead of oleic acid. Measurements of hemodynamic parameters, mean systemic (MAP), pulmonary capillary wedge, and pulmonary artery pressures (PAP), cardiac output, arterial blood gases, extravascular lung waters (EVLW) by thermaldye double indicator dilution techniques and plasma immunoreactive thromboxane B2 ( iTxB2 ), by radioimmunoassay were obtained at zero time (baseline) and 20 min following each oleic acid injection. A new noninvasive technique was employed to measure pulmonary capillary protein leak by the scintigraphic analysis of intravenously administered technetium-99m radiolabeled human serum albumin ( 99mTc -HSA) in the cardiac and lung regions. Oleic acid injection caused a significant dose related fall in MAP (P less than 0.0002), arterial pO2 (P less than 0.0001), and cardiac output (P less than 0.001), and increases in EVLW (P less than 0.003) and plasma iTxB2 (P less than 0.02) in the vehicle pretreated animals, while mean PAP remained unchanged. In contrast, in the indomethacin pretreated dogs, MAP, EVLW, cardiac output, and plasma iTxB2 levels did not change from baseline values and there was an increase in mean PAP. Pulmonary vascular resistance was significantly elevated (P less than 0.05) in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)