Thrombolytic effects of tissue-type and urokinase-type plasminogen activators in rabbits with experimental pulmonary...

The thrombolytic effects of tissue-type of plasminogen activator (t-PA) and urokinase-type of plasminogen activator (u-PA) were studied in experimental rabbit model of pulmonary thromboemboli with or without endotoxin. After intravenous injection of thrombi, we infused recombinant t-PA or double chain u-PA (0.1 mg/kg and 0.3 mg/kg each). Both lungs were histologically examined and the number of thromboemboli/area was calculated. This number of thromboemboli/area thus obtained made the basis for comparing the thrombolytic activity of both t-PA and u-PA. Administration of t-PA at both 0.1 mg/kg and 0.3 mg/kg doses significantly decreased the number of thromboemboli/area comparing to that of u-PA at the respective doses. The treatment of rabbits with endotoxin (1 microgram/kg) increased the number of thromboemboli especially in less than 50 microns diameter of pulmonary microvessels probably due to hypercoagulable and hypofibrinolytic state of rabbits. t-PA, even after endotoxin stimulation, also significantly decreased the thromboemboli comparing to u-PA. From these observations, it is confirmed that t-PA is a much stronger and more effective thrombolytic agent in vivo on the aspects of specific thrombolytic activity and the systemic hypofibrinogenemic effect than u-PA.