Abstract: To investigate the effects of thrombolysis on endothelin release in acute pulmonary embolism and related histopathologic changes in pulmonary arteriols,a canine model of acute pulmonary embolism was designed by injecting autologous blood clot. Fourteen model dogs were randomized to either urokinase treated(UK) or control (CTL) group. Haemodynamic monitoring was performed by introducing catheters through right femoral artery and vein. Arterial endothelin was determined before embolization,before UKinfusion,1.5 and 3.0 h after UKadministration(corresponding time point in CTL ). At the end,the dogs were sacrificed and lung removed for histopathologic and transmission electron microscopic investigations. Plasma endothelin of UKtreated dogs increased progressively with the decrease of pulmonary artery pressure and pulmonary vascular resistance[from baseline (51.63±10.09) pg/Lto (99.25±12.90) pg/L 3.0 h after UKinitiation,P <0.05 and P <0.01 within and between groups respectively]. There were no significant changes in pulmonary artery pressure and pulmonary vascular resistance and plasma endothelin remained unchanged in CTLdogs with time. Histopathologic analysis showed notable patchy hemorrhages with thickened alveolar walls in CTLdogs.In marked contrast with UKdogs with relative normal pulmonary structures,vasoconstrictive sign with degenevated mitochondria in it was demonstrated in the endothelial cells and smooth muscle cells in this group. In conclusion,thrombolytic therapy in acute pulmonary embolism can not only revert the haemodynamic changes,but also relieve the lung tissue and pulmonary arterial injuries; the elevation of arterial plasma endothelin levels in UKdogs may not be the result of pulmonary lesions,but rather an index of pulmonary reperfusion.

Key words: pulmonary embolism, endothelin, ultramicroscopic structure