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.