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

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Abstract
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°C, 3, 000rpm, 10min). 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 (1mm 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 3min. 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 60min. The total dose of UK was 120, 000IU in both AP and UK solutions. The results showed that the plasmin activity of AP solution was maintained up to 90min at 22°C with an additional dose of more than 6, 000IU/ml of UK. In animal experiments, a restoration of the flow was observed more frequently with the AP solution than the UK solution within 15min of the infusion (p<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.

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