Effects of antiplatelet drugs on pulmonary responses to thrombin in anesthetized rabbits

Platelet aggregation and fibrin deposition in the pulmonary circulation may contribute to the pathogenesis of lung injury in the adult respiratory distress syndrome (ARDS). We evaluated the effect of two antiplatelet drugs (forskolin & dipyridamole) on pulmonary responses to intravenous infusion of 100 NIH units of thrombin per kg bw in anesthetized, and ventilated rabbits treated with fibrinolysis inhibitor. Thrombin infusion resulted in pulmonary hypertension and increased arterial CO2 tension (PaCO2) and dead space ventilation (VD/VT). Arterial oxygen tension (PaO2) and numbers of circulating leukocytes and platelets dropped after thrombin infusion. These early hemodynamic changes correlated with histological evidence of entrapped leukocytes in the pulmonary microcirculation and transient alveolar edema. Microthrombi were rarely observed in animals that received thrombin. There was little evidence for endothelial damage or progressive lung water accumulation. Treatment with forskolin or dipyridamole reversed thrombin-induced changes in pulmonary artery pressure, PaCO2, VD/VT and systemic oxygenation. Moreover, forskolin and dipyridamole blunted the drop in circulating leukocytes and prevented the development of alveolar edema following thrombin. The beneficial actions of these agents may be due to interference with the release of mediators from leukocytes or platelets.