Effect of dazoxiben, a specific inhibitor of thromboxane synthetase, on acute pulmonary responses to E. coli endotoxin in anaesthetized cats.

1 The effects of acute pretreatment with the thromboxane synthetase inhibitor dazoxiben 5 mg/kg intravenously (UK 37248‐01) were examined on the acute pulmonary responses of pentobarbitone‐anaesthetized cats to E. coli endotoxin 2 mg/kg intravenously. 2 E. coli endotoxin in control, untreated, cats resulted in a marked pulmonary hypertension, an increase in intra‐tracheal pressure (at a constant pulmonary inflation volume), an increase in both pulmonary arterial and aortic concentrations of thromboxane B2 (TXB2) and a reduction in systematic arterial PO2. 3 Dazoxiben prevented, or markedly reduced, the endotoxin‐ induced pulmonary release of TXB2, the decrease in systematic arterial PO2 and the pulmonary arterial hypertension, but did not modify the increase in intratracheal pressure. 4 These results may suggest that TXA2 is responsible for the endotoxin‐induced pulmonary arterial hypertension but that some other arachidonic acid derivative (prostaglandin F2 alpha) is responsible for the reduced lung compliance that follows the acute administration of E. coli endotoxin.