In order to evaluate the role of leukotrienes in group B streptococcal (GBS) sepsis we studied the effect of a leukotriene receptor antagonist, FPL 57231, on the late hemodynamic changes occurring secondary to an infusion of live GBS. Paralyzed, mechanically ventilated piglets received a continuous intravenous infusion of bacteria (5x107 org/kg/min) while systemic arterial (Psa) and pulmonary artery pressures (Ppa) were measured. To separate the effects of the lipoxygenase products of arachidonic acid from those of the cyclooxygenase by-products, animals in control and treatment groups received indomethacin, a cyclooxygenase blocking agent, 15 min after the infusion of GBS was begun. In addition to GBS and indomethacin, treatment animals received a 30 min infusion of FPL 57231 starting 120 min after the bacterial infusion was begun. All study animals responded to bacteria within 15 min with marked elevation in pulmonary artery pressure (X ± SD) (12 ± 3 to 49 ± 5 mmHg; p < .01), and a decline in PaO2 (84 ± 9 to 49 ± 5 mmHg; p <.01) and cardiac output (0.29 ± 0.04 to 0.18 ± .07 liter/min/kg; p< .01). These changes were reversed by indomethacin. Subsequent values remained relatively stable until approximately 90 min when a gradual decrease in cardiac output (CO) and PaO2, and an increase in Ppa, and calculated systemic (SVR) and pulmonary (PVR) vascular resistances occurred. After the initial increase in TxB2 and 6-keto-PGF(1α), indomethacin treatment resulted in return of these values to baseline with no further increase throughout the study period. FPL 57231 resulted in a significant increase in CO and decrease in P̄pa. These data suggest that FPL 57231 may attenuate the late occurring cardiovascular manifestations of GBS sepsis without modifying TxB2 or 6-keto-PGF(1α) levels. In addition, these results imply that leukotrienes may influence the late hemodynamic manifestations of GBS sepsis.
|Original language||English (US)|
|Number of pages||8|
|Journal||Prostaglandins Leukotrienes and Essential Fatty Acids|
|State||Published - Jan 1 1988|
ASJC Scopus subject areas
- Clinical Biochemistry
- Cell Biology