Hydroxyeicosatetraenoic acids are increased in bronchoalveolar lavage fluid of endotoxemic pigs.
We hypothesized that lipoxygenase metabolites of arachidonic acid might be produced during endotoxin-induced acute respiratory failure (ARF) observed in young pigs. We used radioimmunoassay (RIA) to determine the presence of 5-hydroxyeicosatetraenoic acid (5-HETE), 12-HETE, and 15-HETE in bronchoalveolar lavage fluid (BALF) of saline (n = 12)- and endotoxin (n = 18)-treated pigs. Endotoxin, infused at 5 micrograms/kg for 1 hr followed by 2 micrograms/kg/hr for an average of 3 hrs, caused pulmonary hypertension, a biphasic increase in pulmonary vascular resistance, hypoxemia, bronchoconstriction, leukopenia, and thrombocytopenia. Relative to saline controls, the levels of immunoreactive (i)-5-HETE (816 +/- 209 pg/ml), i-12-HETE (1589 +/- 517 pg/ml), and i-15-HETE (448 +/- 78 pg/ml) were significantly (P less than 0.05) increased in BALF recovered from endotoxemic pigs at postmortem. Relative to control BALF i-HETE concentrations, the endotoxin values were 3.5x, 5.1x, and 2.8x higher for i-5-HETE, i-12-HETE, and i-15-HETE, respectively. We conclude that during porcine endotoxemia, the 5-, 12-, and 15-lipoxygenase pathways are activated and that HETES might be involved in the pathophysiology of endotoxin-induced ARF.
D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid / Q000378:metabolism*; D004731:Endotoxins / Q000097:blood; D004926:Escherichia coli; D006893:Hydroxyeicosatetraenoic Acids / Q000378:metabolism*; D008084:Lipoxygenase / Q000378:metabolism; D011863:Radioimmunoassay; D012128:Respiratory Distress Syndrome / Q000209:etiology / Q000378:metabolism*; D013552:Swine
D001095:Arachidonic Acids; D004731:Endotoxins; D006893:Hydroxyeicosatetraenoic Acids; D008084:Lipoxygenase