LY171883 preserves mesenteric perfusion in porcine endotoxic shock

Superior mesenteric arterial perfusion ( Q ̇) decreases and gut intramucosal hydrogen ion concentration, [H⁺], increases in resuscitated normodynamic endotoxic pigs. The present study tested the hypothesis that these adverse phenomena can be prevented by pretreatment with LY171883, a specific leukotriene (LT) D₄/E₄ receptor antagonist. Pentobarbital-anesthetized pigs (14-18 kg) were instrumented to permit measurement of Q ̇ (ultrasonic flow probe) and [H⁺] (tonometer). Mesenteric O₂ delivery (ḊO₂) and consumption (V̇O₂) were calculated from the O₂ contents of arterial and superior mesenteric venous blood. At t = -20 min, groups (N = 6) of pigs were pretreated with LY171883 (10 mg/kg) or vehicle. At t = 0 min, the pigs were infused over 20 min with lipopolysaccharide (LPS; 150 μg/kg) and resuscitated for 2 hr with saline (1.2 ml/kg min). Irrespective of treatment group, mean arterial pressure and systemic vascular resistance index decreased significantly after infusion of LPS. In general, cardiac index (CI) was well preserved, although in controls at t = 20, 100, and 120 min, CI decreased significantly with respect to the t = 0 min value. Normal mesenteric Q ̇ and ḊO₂ were maintained in the LY171883 group, whereas, in controls, these parameters decreased significantly. Mesenteric V̇O₂ increased transiently but significantly in controls; this phenomenon was abrograted by the LT receptor antagonist. In controls, intramucosal [H⁺] increased by almost threefold; this adverse effect was significantly ameliorated by LY171883. These data suggest that decreased mesenteric Q ̇ and increased intramucosal [H⁺] may be mediated by LT in this porcine endotoxic shock model.