Hydroxyeicosatetraenoic acids are increased in bronchoalveolar lavage fluid of endotoxemic pigs

Abstract

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 μg/kg for 1 hr followed by 2 μg/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 <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.