Thromboxane and prostacyclin production during septic shock.
We investigated a rat fecal peritonitis model of acute intraabdominal sepsis in order to evaluate the potential role of arachidonic acid metabolites in septic shock. Immunoreactive TxB2, the stable metabolite of thromboxane A2, and i6-keto-PGF1 alpha, the stable metabolite of prostacyclin, were measured by radioimmunoassay. Plasma levels of iTxB2 rapidly increased from nondetectable (ND less than 200 pg/ml) to 1,052 +/- 208 pg/ml, one hour after feces injection. iTxB2 then increased to 1,681 +/- 248 pg/ml at four hours and remained unchanged through six hours. Plasma i6-keto-PGF1 alpha increased from ND to 3,848 +/- 489 pg/ml a one hour. Four hours after feces, i6-keto-PGF1 alpha levels rose to 7, 450 +/- 933 pg/ml then continued to rise to 9,465 +/- 792 pg/ml at six hours. Either essential fatty acid deficiency (arachidonic acid depletion) or indomethacin treatment (cyclo-oxygenase inhibition) significantly decreased (P less than 0.01) the elevation of plasma iTxB2 and i6-keto-PGF1 alpha associated with fecal peritonitis. Thrombocytopenia occurred within six hours after injection of feces and was significantly improved (P less than 0.05) by indomethacin. Elevated fibrin degradation products at six hours (18 +/- 3 micrograms/ml) were significantly reduced in essential fatty acid-deficient (7 +/- 2 micrograms/ml; P less than 0.05) and indomethacin-treated (4 +/- 0.7 micrograms/ml; P less than 0.01) rats. Survival time (8.6 +/- 0.2 hours) was significantly enhanced by essential fatty acid-deficiency (10.2 +/- 0.4 hours; P less than 0.01) or indomethacin treatment (13.3 +/- 0.6 hours; P less than 0.01). These studies show that fecal peritonitis is associated with increased synthesis of thromboxane A2 and prostacyclin and suggest that these arachidonic acid metabolites may play a role in the pathophysiology of septic shock.
D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood; D000818:Animals; D011464:Epoprostenol / Q000096:biosynthesis*; D005228:Fatty Acids, Essential / Q000172:deficiency; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000032:analysis; D007213:Indomethacin / Q000627:therapeutic use; D010538:Peritonitis / Q000503:physiopathology; D011453:Prostaglandins / Q000096:biosynthesis*; D051381:Rats; D011919:Rats, Inbred Strains; D012772:Shock, Septic / Q000378:metabolism* / Q000503:physiopathology; D013921:Thrombocytopenia / Q000188:drug therapy; D013928:Thromboxane A2 / Q000096:biosynthesis* / Q000097:blood; D013931:Thromboxanes / Q000096:biosynthesis*; D013997:Time Factors
D005228:Fatty Acids, Essential; D005338:Fibrin Fibrinogen Degradation Products; D011453:Prostaglandins; D013931:Thromboxanes; D013928:Thromboxane A2; D015121:6-Ketoprostaglandin F1 alpha; D011464:Epoprostenol; D007213:Indomethacin