PRINCIPLES OF THROMBOLYSIS IN PULMONARY-EMBOLISM

A canine model of pulmonary embolism, induced by injection of autologous radioactive blood clots, was used to investigate principles of thrombolysis in pulmonary embolism. One study compared recombinant tissue plasminogen activator (rtPA) with heparin in the treatment of pulmonary embolism. This study also compared the efficacy of rtPA (1 mg/kg) given over 15 min (rtPA15) to the same total dose infused over 90 min. Compared with heparin, both rtPA regimens induced marked pulmonary thrombolysis. During drug infusion, the rate of thrombolysis was increased 2-fold with rtPA15. A 2nd canine study investigated the physiologic mechanism of the decrease in pulmonary artery pressure with rtPA. The pattern of hemodynamic improvement with rtPA indicated that pulmonary thrombolysis predominantly occurred in partially, rather than totally, obstructed vascular units. A 3rd canine study compared rtPA and high-dose urokinase (UK) in treatment of pulmonary embolism. Both rtPA regimens were superior to UK in inducing pulmonary thrombolysis and improving pulmonary hemodynamics. Most recently, the effects of flow dynamics on rtPA-induced pulmonary thrombolysis were investigated, and it was demonstrated that an increase in cardiac output markedly enhanced rtPA-induced pulmonary thrombolysis. Most likely, the increase in cardiac output increased thrombolysis by enhancing delivery of rtPA to thrombus in partially obstructed vascular units.