Inhibition of thromboxane synthesis reduces endotoxin-induced right ventricular failure in sheep

Background and Methods: There is a marked decrease of the right ventricular ejection fraction after the administration of a bolus of endotoxin to sheep. This hemodynamic response may be the result of thromboxane-mediated pulmonary hypertension. Right ventricular function was studied in an ovine model after the administration of endotoxin (1 μg/kg Escherichia coli) with and without pretreatment with OKY-046, a selective thromboxane synthetase inhibitor. Results: OKY-046 attenuated the endotoxin-induced increase in pulmonary arterial pressure and prevented the early decreases in right ventricular ejection fraction and cardiac output. However, thromboxane synthetase inhibition failed to prevent endotoxin-induced hypoxemia. The marked increase in plasma thromboxane concentrations, which is usually seen after the administration of endotoxin, was prevented by pretreating the animals with OKY-046. On the other hand, increased plasma prostacyclin concentrations were observed in sheep treated with the thromboxane synthetase inhibitor. Conclusion: This series of experiments shows that the early endotoxin-induced decrease in right ventricular ejection fraction can be alleviated by the application of OKY-046.