Role of thromboxane (Tx) A2 in guinea pig forssman shock and the effect of OKY-046, TX A2 synthetase inhibitor

To study the role of thromboxane (Tx) A₂ in Forssman systemic shock (FSS) in guinea pig, the effect of (E)-3-p(1H-Imidazol-1-ylmethyl) phenyl]-2-propenoic acid hydrochloride (OKY-046), a specific Tx A₂ synthetase inhibitor, was studied. OKY-046 administered intravenously clearly prolonged survival time and protected against fatal shock. In shocked animals, definite decreases in serum complement hemolytic activity (CH50), leucocyte counts and platelet counts and an increase in lactate dehydrogenase (LDH) activity were observed. In addition, a significant increase of Tx B₂ and incoagulability of blood were observed after shock. Whereas OKY-046 had no effect on the decreases in CH₅₀, platelet counts and leucocyte counts, it inhibited the increase of Tx B₂ and increased the amount of 6-keto PG F_1α. When Forssman antibody (half a lethal dose) was injected, a diphasic increase in airway resistance was observed. OKY-046 inhibited this diphasic increase in airway resistance. These data suggest a pathophysiological role for Tx A₂ in FSS. OKY-046 inhibited the Forssman antibody induced respiratory disorders probably due to the inhibition of Tx A₂ synthesis after shock.