Endotoxin-Induced Changes in Pulmonary Hemodynamics and Respiratory Mechanics

We investigated the role of leukotrienes and cyclooxygenase products in endotoxin-induced pulmonary vascular and airway changes. In 11 conscious sheep, measurements of pulmonary vascular resistance (PVR), lung resistance (Rl), arterial PO2, leukocyte count (WBC), and plasma thromboxane B2 (TxB2), 6-keto-PgF1α and PgF2α were obtained, before and at predetermined intervals after a 10-min infusion of E. coli endotoxin (0.3 µg/kg). On a separate occasion, 5 sheep received an infusion of the leukotriene end-organ receptor antagonist FPL-57231 (0.7 to 1 mg/kg/min), before and for as long as 4 h after endotoxin infusion; and 6 sheep received a single injection of the cyclooxygenase inhibitor indomethacin (2 mg/kg) 1 h before endotoxin infusion. Endotoxin caused a biphasic response with an increase in mean PVR and Rl to 441 and 353% of baseline, respectively, during the early phase (0 to 1 h), and lesser increases to 168 and 195% of baseline during the late phase (1.5 to 4 h). These changes were associated with m...