Prostacyclin and thromboxane A2 in septic shock: species differences.

Prostacyclin and thromboxane A2 have been implicated as mediators of septic shock. Correlations between the human prostanoid response to sepsis and experimental paradigms are poorly understood. The purpose of this study was to compare changes in plasma levels of prostaglandin 6-keto-F1 alpha (PGI) and thromboxane B2 (TxB) during septic shock in Sprague-Dawley rats, domestic pigs, mongrel dogs, and man. Severe sepsis followed by septic shock (systolic BP less than 90 mmHg) was induced in rats by inoculation of 1.0 X 10(9) Aeromonas hydrophila, in pigs by graded IV infusion of 1.0 X 10(9)/ml A. hydrophila; and in dogs by an IV bolus injection of 5.0 X 10(9)/ml Escherichia coli. Plasma PGI and TxB (pg/ml) were measured by radioimmunoassay in control, septic, and septic shock experimental blood samples, and in normal controls, severly septic, and septic shock (systolic BP less than 90 mmHg) S.I.C.U. patients. Control, septic, and septic shock TxB levels in the dog and the pig were significantly greater than in the rat and man. PGI levels in the dog were significantly greater than in other species. TxB increased significantly in murine sepsis and PGI increased significantly in sepsis and septic shock. TxB increased during porcine sepsis and septic shock. In man, both PGI and TxB were significantly increased in severe sepsis, compared to normal controls, but only PGI was significantly higher in septic shock versus normotensive sepsis. Patterns of change in TxB/PGI ratios were similar for all species studied. Changes in PGI in the porcine septic experiments most closely paralleled those observed clinically.