The role of thromboxane in primate endotoxin shock.
Previous studies have suggested an important role of thromboxane (Tx) in the pathogenesis of endotoxin shock in the rat. The present study evaluated the role of thromboxane in an LD70 primate model of endotoxin shock by administering 6 mg/kg of endotoxin to three groups of animals that were pretreated with either saline (5 ml), OKY 1581 (2 mg/kg, 10 min prior), or imidazole (25 mg/kg/hr starting 30 min prior), groups I, II, and III, respectively. There were significant differences between the groups with respect to changes in MAP, PAP, and CO. OKY 1581 effectively blocked endotoxin-induced increase in plasma Tx. However, as a result of shunting of the endoperoxides into the prostacyclin pathway, there was a greater increase in plasma 6-keto PGF1 alpha, the stable hydrolysis product of prostacyclin. Imidazole augmented the formation of both prostacyclin and Tx. Despite the differences in plasma prostanoids, there was no difference between the groups with respect to changes in platelet or WBC counts, nor in survival: I (4/10); II (4/10); III (2/6).


CONCLUSIONS
(i) endotoxin-induced neutropenia and decrease in the platelet count are not Tx mediated; (ii) Tx is not solely responsible for the decrease in CO during endotoxin shock; (iii) it is possible to prevent endotoxin-induced increase in the PAP by either blocking Tx formation or by increasing endogenous PGI2 production; and (iv) Tx may not be a major contributing factor in the mortality of endotoxin shock in baboons.
D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood; D000818:Animals; D006439:Hemodynamics; D007093:Imidazoles / Q000494:pharmacology; D007958:Leukocyte Count; D008297:Male; D008689:Methacrylates / Q000494:pharmacology; D010215:Papio; D011897:Random Allocation; D012772:Shock, Septic / Q000378:metabolism* / Q000401:mortality; D013929:Thromboxane B2 / Q000037:antagonists & inhibitors / Q000097:blood / Q000378:metabolism*; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors; D013931:Thromboxanes / Q000378:metabolism*; D013997:Time Factors
D007093:Imidazoles; D008689:Methacrylates; D013931:Thromboxanes; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; C031517:2-methyl-3-(4-(3-pyridinylmethyl)phenyl)-2-propenoic acid; C029899:imidazole; D013930:Thromboxane-A Synthase