Potential thrombolysis under selective infusion of autologous plasmin (AP) solution

Thrombolytic therapy with plasminogen activators, urokinase (UK) and streptokinase (SK), can produce serious complications such as systemic bleeding. We have developed an autologous plasmin (AP) solution as a new potential thrombolytic agent and evaluated its efficacy in animal experiments. The AP solution was prepared by the addition of UK to autologous plasma separated by centrifugation (4 degrees C, 3,000 rpm, 10 min). The plasmin activity in the AP solution was measured by the plasminogen-free fibrin plate method and spectrophotometric assay with the chromogenic substrate S-2251. In animal experiments, the femoral artery of anesthetized mongrel dogs (n = 20) was constricted by ligation (1 mm in diameter) and a fibrin clot was embolized into this site. Either AP solution (n = 8), UK solution (n = 6) or saline (n = 6) was selectively infused for 3 min. Prior to the infusion, a temporary flow obstruction was made by inflation of a balloon tip catheter located proximal to the embolized site. The thrombolytic effect was sequentially observed with an ultrasound flow meter for up to 60 min. The total dose of UK was 120,000 IU in both AP and UK solutions. The results showed that the plasmin activity of AP solution was maintained up to 90 min at 22 degrees C with an additional dose of more than 6,000 IU/ml of UK. In animal experiments, a restoration of the flow was observed more frequently with the AP solution than the UK solution within 15 min of the infusion (p less than 0.01). Thus, a high thrombolytic efficacy was observed with a selective infusion of rich, activated plasmin (AP) solution. This treatment could be applied as a new approach for arterial thrombolysis.