Effects of a Leukotriene Antagonist on the Early Hemodynamic Manifestations of Group B Streptococcal Sepsis in Piglets

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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 × 108 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-PGF1α 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 < 0.001), and a decline in PaO2 (79 ± 9 to 44 ± 5 mm Hg) (p < 0.001) and a cardiac output (0.27 ± 0.07 to 0.15 ± 0.06 liter/min/kg) (p < 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 < 0.01) by 60 min, while treatment group animals maintained a pH of 7.3 ± 0.23. Thromboxane B2 and 6-keto PGF1α 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 < 0.01). These data suggest that FPL 57231 may attenuate the early cardiovascular changes accompanying GBS infection and positively influence survival without modifying thromboxane or 6-keto PGF1α levels. These results imply that leukotrienes influence the early hemodynamic manifestations of GBS sepsis.

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