The effect of prostacyclin on increased hydraulic conductivity of pulmonary exchange vessels following microembolization in dogs.

Prostacyclin (PG I2) generated by vascular endothelium is a strong antiaggregating substance. As platelet aggregation and release of humoral factor(s) have been reported to be crucial in the pathogenesis of acute lung injury following pulmonary microembolization, PG I2 could have a protective effect against microembolic lung vascular injury. Following unilateral microembolization, we have observed a large increase in the filtration coefficient in the nonembolized lung with a significant increase in 6-keto PG F1 alpha, the stable metabolite of PG I2, in arterial blood. The pretreatment with indomethacin (10 mg/kg) prevented the increase in 6-keto PG F1 alpha and potentiated the lung injury after microembolization. Exogenously administered PG I2 (20 ng/kg/min) prevented completely the increase in the filtration coefficient without any effects on hemodynamics, although these effects of indomethacin and PG I2 did not relate to their effects on platelet aggregation. Based on these results, we could conclude that prostacyclin could play an important role in preserving cell integrity of the lung and in prevention of increased lung vascular permeability following pulmonary microembolization.