Effect of LTB4 receptor antagonists in endotoxic shock in the rat

This study examined 1) the effects of infusion of LTB4 and 2) the potential role of LTB4 in the sequelae to endotoxic shock in the rat. Control rats were anesthetized with Ketamine/xylazine and given LTB4 (2 micrograms/kg) bolus i.v. followed by a 1 microgram/kg/min infusion for 10 min. LTB4 induced systemic hypotension and a three-fold increase in circulating band neutrophils which contributed to a 70% increase (P less than 0.05) in the total peripheral neutrophil count. LTB4 did not cause changes in circulating mature (segmented) neutrophils, lymphocytes, platelets, or hematocrits. Pretreatment (1 min) with LY233978, an LTB4 antagonist (10 mg/kg bolus i.v.), inhibited LTB4-induced systemic hypotension (-16.1 +/- 6.1 mmHg [n = 3] vs. -38.8 +/- 5.9 mmHg [n = 4], P less than 0.05). Salmonella enteritidis endotoxin (10 mg/kg bolus i.v.) induced systemic hypotension, hemoconcentration, leukopenia, and thrombocytopenia, which was greatest at 5 and 15 min postendotoxin. The leukopenia was characterized by lymphopenia, band neutropenia, and segmented neutropenia. LY233978 (10 mg/kg bolus i.v. immediately before endotoxin administration and followed by an infusion at 0.67 mg/kg/min for 90 min) attenuated endotoxin-induced hemoconcentration at 60 and 90 min postendotoxin (P less than 0.05), and systemic hypotension at 15 min postendotoxin (P less than 0.05). The LTB4-receptor antagonist LY255283 (10 mg/kg bolus i.v., 10 min before endotoxin followed by a 5 mg/kg bolus i.v. 30 min postendotoxin) completely inhibited endotoxin-induced systemic hypotension and partially attenuated endotoxin-induced hemoconcentration from 15 min to 90 min postendotoxin (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)