The potential beneficial effect of a thromboxane synthetase inhibitor, OKY-1581, on increased lung vascular permeability in experimental pulmonary microembolization in dogs.

Abstract

To evaluate the potential beneficial effect of a thromboxane synthetase inhibitor, OKY-1581, on increased pulmonary vascular permeability in pulmonary microembolization, we have measured the filtration coefficient in the nonembolized lung after unilateral microembolization in dogs. The unilateral microembolization caused marked elevations in pulmonary artery pressure and blood flow to the nonembolized lung, while pulmonary venous pressure in nonembolized lung did not change. The pulmonary vascular resistance in nonembolized lung did not increase significantly. The filtration coefficient (kf) in nonembolized lung increased to 0.14 +/- 0.02 from te base line value of 0.07 +/- 0.01 ml/min/mmHg/100 g at 30 min after microembolization when the initial hemodynamic changes reduced toward the base line value. In OKY-1581 treated dogs, similar hemodynamic changes did not result in the filtration coefficient in nonembolized lung. Platelet aggregagation was also inhibited after microembolization in OKY-1581 treated dogs. Based on these results, we could conclude that OKY-1581 will serve as a potent beneficial protective drug against pulmonary edema by inhibiting the release of thromboxane A2 following microembolization in the pulmonary vascular bed.