Assessment of bronchoalveolar lavage fluid and plasma for sulfidopeptide leukotrienes during endotoxemia in pigs

Abstract

We hypothesized that sulfidopeptide leukotrienes (LTC₄, LTD₄, LTE₄) might be important to the pathophysiology of endotoxin-induced acute respiratory failure (ARF) observed in young pigs. We used radioimmunoassay (RIA), reverse-phase high performance liquid chromatography (RP-HPLC) and guinea pig ileum bioassay techniques to determine the presence of sulfidopeptide leukotrienes in bronchoalveolar lavage fluid (BALF) and plasma of saline(n=12)- and endotoxin(n=12)-treated pigs. Endotoxin, infused at 5 μg/kg for 1 hr followed by 2 μg/kg/hr for 3.5 hrs, caused pulmonary hypertension, a biphasic increase in systemic and pulmonary vascular resistances, hypoxemia, bronchoconstriction and hemo-concentration. The levels of immunoreactive sulfidopeptide leukotrienes were not significantly increased in BALF recovered from endotoxemic pigs. Arterial plasma samples (collected at 0.5 hr intervals for 4.5 hrs) were below the detectable limits of the RIA. During RP-HPLC, ethanol extracted BALF failed to show an ultraviolet (UV) absorbance peak (280 nm) that was coincident with authentic standards. Concentrated BALF samples and BALF eluate fractions (collected at a retention time consistent with authentic LTC₄) failed to cause a sustained contraction of guinea pig ileum. We conclude that sulfidopeptide leukotrienes are not increased in BALF or plasma recovered from endotoxemic pigs and that these lipoxygenase metabolites might not be important factors contributing to the pathophysiology of endotoxin-induced ARF. An alternate explanation is that the sulfidopeptide leukotrienes are rapidly metabolized so as to be undetectable by the methods employed.