Cardiovascular changes in group B streptococcal sepsis in the piglet: response to indomethacin and relationship to prostacyclin and thromboxane A2.
Seventeen piglets were infected with a continuous intravenous infusion of live group B beta-hemolytic streptococci (GBS). Hemodynamic changes were recorded, and blood samples were drawn for measurement of thromboxane B2 (TxB2) (stable metabolite of thromboxane A2) and 6-keto-PGF1 alpha (stable metabolite of prostacyclin). Control animals (n = 9) received only bacteria, while treatment animals (n = 8) received indomethacin, 3 mg/kg IV, 15 min after the start of the bacterial infusion. Control animals responded to the bacteria within 15 min with marked elevation in mean pulmonary artery pressure (Ppa) from 15 +/- 8 to 39 +/- 6 mm Hg and decline in PaO2 from 80 +/- 11 to 51 +/- 6 mm Hg and cardiac output (CO) from 0.24 +/- 0.07 to 0.13 +/- 0.07 liters/min/kg. Mean arterial blood pressure (AoP) significantly decreased from baseline value of 95 +/- 13 to 51 +/- 32 mm Hg by 180 min. In animals treated with indomethacin, these changes were reversed or significantly attenuated. The hemodynamic changes were associated temporally with elevations in plasma concentrations of TxB2 or 6-keto-PGF1 alpha. In the first 60 min, TxB2 levels in both groups correlated with Ppa (r = 0.72, p less than 0.001) and PaO2 (r = -0.60, p less than 0.001). A strong negative correlation between TxB2 and CO was observed over the first 180 min (r = -0.73, p less than 0.001). There was a statistically significant correlation between AoP and 6-keto-PGF1 alpha concentration between 60 and 180 min (r = -0.54, p less than 0.002). Indomethacin improved the hemodynamic function in this model of GBS sepsis.(ABSTRACT TRUNCATED AT 250 WORDS)
D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D011464:Epoprostenol / Q000037:antagonists & inhibitors*; D006439:Hemodynamics / Q000187:drug effects*; D007213:Indomethacin / Q000494:pharmacology / Q000627:therapeutic use*; D013290:Streptococcal Infections / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D013292:Streptococcus agalactiae; D013552:Swine; D013928:Thromboxane A2 / Q000037:antagonists & inhibitors*; D013929:Thromboxane B2 / Q000097:blood; D013931:Thromboxanes / Q000037:antagonists & inhibitors*; D013997:Time Factors
D013931:Thromboxanes; D013929:Thromboxane B2; D013928:Thromboxane A2; D015121:6-Ketoprostaglandin F1 alpha; D011464:Epoprostenol; D007213:Indomethacin