Leukotriene C₄ induces mesenteric hypoperfusion and intestinal intramural acidosis in pigs

We examined the effect of intravenous infusion of graded doses of authentic leukotriene (LT) C₄ on several physiological variables in pentobarbital-anesthetized immature swine. Mesenteric blood flow (Q̊sma) was measured using an ultrasonic flow probe and ileal intramucosal hydrogen ion concentration ([H⁺]_I) was estimated tonometrically. Three groups were studied. Pigs in Group I (n = 6) were infused beginning at t = 0 min with increasing doses (0.03-1.0 μg/kg-min) of LTC₄, each dose being administered for 10 min. Pigs in Group II (n = 6) were infused with LTC₄ as above, but were pre- and post-treated with a specific sulfidopeptide LT receptor antagonist, LY203647 (30 mg/kg bolus and then 10 mg/kg-hr) beginning at t = -20 min. Pigs in Group III (n = 4) received only normal saline (5 ml/kg-h). Infusing LTC₄ significantly decreased Q̊sma and mesenteric oxygen uptake and significantly increased ileal [H⁺]_I. These changes were prevented by LY203647. These data support the idea that sulfidopeptide LT are capable of causing mesenteric ischemia and that this phenomenon can be blocked by LY203647.