The sulfidopeptide leukotrienes (LT) have been implicated as important pathophysiological mediators in septic shock. To further define the role of these compounds, we utilized a porcine endotoxicosis model to study the effects of pre- and concurrent treatment with LY203647, a novel LT receptor antagonist. Pentobarbital-anesthetized pigs (13-20 kg) were mechanically ventilated with 100% O2. Superior mesenteric arterial flow (Q̇sma) was measured using an ultrasonic flow probe. Ileal intramucosal hydrogen ion concentration, [H+]1, was estimated tonometrically. Pigs in groups I and II were infused with endotoxin (250 μg/kg) and resuscitated with saline (1.2 ml/kg min). Group I (n = 8) were controls; Group II (n = 8) were pretreated with LY203647 (30 mg/kg bolus, then 10 mg/kg h). Treatment with LY203647 persistently and significantly (P < .05) improved post-LPS pO2 and transiently improved Q̇sma. Treatment with LY203647 did not affect [H+]1. Lung extravascular wet-to-dry weight ratios were 7.13 ± .33 and 5.43 ± .09 in groups I and II, respectively (P < .001). These data suggest that sulfidopeptide LT are important mediators of key pathophysiologic events in this porcine model of endotoxic shock and the adult respiratory distress syndrome (ARDS).
|Original language||English (US)|
|Number of pages||10|
|State||Published - Jan 1 1991|
- adult respiratory distress syndrome
- septic shock
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine