Effect of leukotriene inhibitor LY-171883 on the pulmonary response to Escherichia coli endotoxemia.

Abstract

The effect of the leukotriene D4 (LTD4) receptor antagonist, LY-171883, on the respiratory and cardiovascular changes in endotoxemia was studied in 20 unanesthetized sheep. In group 1 (n = 2), 4 mg/kg LY-171883 was injected iv. In group 2 (n = 12), Escherichia coli endotoxin (1 micrograms/kg) was infused iv, and in group 3 (n = 6), 4 mg/kg LY-171883 was administered 15 min before and 30 min after the same dose of endotoxin. Infusion of LY-171883 in group 1 did not alter baseline ventilatory and cardiovascular measurements. A two-phase pulmonary response was observed in group 2: an early pulmonary hypertension phase in which pulmonary artery pressure (PAP) increased from 18.7 to 51.2 mm Hg (p less than .001), with a fall in cardiac index (CI) from 171 to 114 ml/min.kg (p less than .01). The ratio of peak inspiratory/expiratory flow rate (PIF/PEF) increased from 1.08 to 1.35 (p less than .01) and the respiratory rate from 50 to 70 breath/min (p less than .005) 30 min postendotoxin. The flow rate measured at midexpiration time (V50) decreased from 81% to 25% of its peak expiration (p less than .001) and the airway resistance increased from 3.8 to 32.7 cm H2O/L.sec (p less than .001). The second permeability phase was characterized by an increase in pulmonary lymph flow (QL) from 8.5 to 35.2 ml/h (p less than .01), a decrease in PaO2 from 76 to 61 torr (p less than .01), and an increase in pulmonary shunt ratio (Qsp/Qt) from 16% to 31% (p less than .005).(ABSTRACT TRUNCATED AT 250 WORDS)