| Abstract: | In order to evaluate the influence of leukotrienes on group B streptococcal (GBS) sepsis we studied the effect of a leukotriene antagonist, FPL 57231, on the early hemodynamic changes occurring secondary to an infusion of live GBS. Paralyzed, mechanically ventilated piglets received a continuous intravenous infusion of bacteria (5 X 10(8) org/kg/min) while systemic arterial pressure and pulmonary artery pressure were measured continuously. Cardiac output was measured by thermodilution; and plasma samples for determination of thromboxane B2 and 6-keto-PGF1 alpha were taken at preset intervals. In addition to GBS, treatment animals received a continuous infusion of FPL 57231 starting 15 min after the bacterial infusion was begun. Study animals as a whole responded to bacteria within 15 min with a marked elevation in pulmonary artery pressure from 13.6 +/- 4 to 44.6 +/- 6 mm Hg (p less than 0.001), and a decline in PaO2 (79 +/- 9 to 44 +/- 5 mm Hg) (p less than 0.001) and a cardiac output (0.27 +/- 0.07 to 0.15 +/- 0.06 liter/min/kg) (p less than 0.0001). In animals treated with FPL 57231 these changes were reversed or significantly attenuated by 60 min. In the control group pH deteriorated significantly to 7.17 +/- 0.1 compared to baseline values (p less than 0.01) by 60 min, while treatment group animals maintained a pH of 7.3 +/- 0.23. Thromboxane B2 and 6-keto PGF1 alpha were similar in both groups and did not change during the study period. In addition, survival was significantly longer in treatment (191 +/- 44 min) compared to control animals (100 +/- 32 min) (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) |
