Arterial thrombus dissolution in vivo using a transducer-tipped, high-frequency ultrasound catheter and local low-dose urokinase delivery

Purpose: To examine the hypothesis that a transducer-tipped high-frequency ultrasound drug-delivery catheter may augment the thrombolytic effects of l ocally delivered low-dose urokinase and result in improved recanalization r ates and reduced residual thrombotic burden. Methods: Thrombi were induced in situ bilaterally in 5- to 6-cm-long segmen ts of the superficial femoral arteries in 9 dogs by intraluminal thermal da mage and injection of thrombin. A transducer-tipped high-frequency local dr ug-delivery catheter was applied at 1.1 MHz and 0.6 W for 60 minutes to one superficial femoral artery segment, and an identical catheter with an inac tivated ultrasound transducer was used to treat the contralateral control s egment. Urokinase (5000 IU/kg) was delivered bilaterally into the thrombi d uring the treatment interval. Results: Angiography documented TIMI grade 2 or 3 flow in 9 (100%) segments in the ultrasound-treated group versus 6 (67%) of the controls (no ultraso und) (p = 0.058). Angiographically detected distal embolization was found i n 2 ultrasound-treated segments compared with 5 controls (p = 0.02). Protru ding or occlusive thrombi were seen angioscopically in 8 (89%) control segm ents but in only 1 (11%) of the ultrasound-treated arteries (p < 0.001). By histopathology, 7 (78%) segments in the control group had occlusive thromb i, whereas only 3 nonocclusive thrombi were found in the ultrasound-treatme nt group (p < 0.001). Conclusions: Catheter-delivered high-frequency ultrasound and local low-dos e urokinase infusion is efficacious for the treatment of acute thrombotic o cclusions as evaluated by angiography, angioscopy, and histopathology.