α 2-Antiplasmin plays a significant role in acute pulmonary embolism

Abstract

The importance of pulmonary embolism (PE) due to venous thrombosis is recognized in the treatment of vascular diseases. We have investigated the physiological effects of plasmin generation in experimental acute PE using mice defi-cient in plasminogen (Pig -/-) or α 2-antiplasmin (α 2-AP -/-). PE was induced by continuous induction of venous thrombus in the left jugular vein by endothelial injury due to photochemical reaction. The mortality of wild-type mice was 68.8% at 2 h after the initiation of venous thrombosis and it was significantly reduced in α 2-AP -/- mice (41.7%). In contrast, Plg -/- mice did not survive. Histological evidence of thromboembolism in the lung was obtained in all mice. However, whereas a strict thromboembolism was observed in Pig mice, only a few thrombi were detected in the lungs of α 2-AP -/- mice. Plasma fibrinogen levels measured in mice were not different. When α 2-AP was infused in α 2-AP -/- mice, the mortality was indis-tinguishable from wild-type mice. Tissue-type plasminogen activator (tPA) did not reduce the mortality due to acute PE in wild-type mice. However, in α 2-AP -/- mice, tPA (0.52 mgkg -1) significantly decreased the mortality compared with that of α 2-AP -/- mice without tPA. The bleeding time was not significantly prolonged in either type of mice treated with tPA. The lack of plasminogen increases the mortality due to acute PE while a lack of α 2-AP decreases the mortality rate, which can be further reduced by tPA administration. Therefore, the combination of inhibition of α 2-AP with thrombolytic therapy could be beneficial in the treatment of acute PE. © 2003 International Society on Thrombosis and Haemostasis.