Effect of cyclooxygenase and lipoxygenase products on pulmonary function in group B streptococcal sepsis1

The effects of the cyclooxygenase inhibitor, indomethacin, and the leukotriene receptor antagonist, FPL 57231, on changes in dynamic lung compliance and pulmonary resistance associated with a 1-h infusion of live group B streptococci were evaluated in mechanically ventilated piglets. To define mediators of early changes in lung function, animals were given an infusion of either FPL 57231 or indomethacin beginning 15 min after the infusion of group B streptococci was begun. These groups were compared to an untreated group who received only group B streptococci. Within 15 min of starting the bacterial infusion, all groups showed significant increases in pulmonary artery pressure, pulmonary artery wedge pressure, total pulmonary resistance, transpulmonary pressure, and thromboxane B₂, and decreases in tidal volume, dynamic lung compliance, and PaO₂. After treatment with indomethacin there were significant decreases in pulmonary artery pressure (mean ± SEM; 48 ± 1 to 22 ± 3 mm Hg, p<0.001), pulmonary artery wedge pressure (7.5 ± 1.3 to 2.2 ± 0.4 mm Hg, p < 0.001) and thromboxane B₂ (6.51 ± 1.56 to 1.01 ± 0.27 ng/ml, p < 0.01) and an increase in dynamic lung compliance (1.10 ± 0.10 to 1.28 ± 0.14 ml/cm H₂O/kg, p < 0.01) over the study period. Total pulmonary resistance decreased significantly (18.7 ± 1.8 to 15.7 ± 1.5 cm H₂O/liter/s, p <0.02) only at 60 min. In animals treated with FPL 57231 only pulmonary artery pressure (46 ± 3 to 30 ± 2 mm Hg, p < 0.05) and pulmonary artery wedge pressure (7.5 ± 0.8 to 4.0 ± 0.9 mm Hg, p < 0.01) decreased. These data suggest that cyclooxygenase products of arachidonic acid metabolism play a role in the early changes in pulmonary mechanics in group B streptococci sepsis.