Arterial thrombus dissolution in vivo using a transducer-tipped, high-frequency ultrasound catheter and local low-dose urokinase delivery.
OBJECTIVE
To examine the hypothesis that a transducer-tipped high-frequency ultrasound drug-delivery catheter may augment the thrombolytic effects of locally delivered low-dose urokinase and result in improved recanalization rates and reduced residual thrombotic burden.


METHODS
Thrombi were induced in situ bilaterally in 5- to 6-cm-long segments of the superficial femoral arteries in 9 dogs by intraluminal thermal damage and injection of thrombin. A transducer-tipped high-frequency local drug-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 inactivated ultrasound transducer was used to treat the contralateral control segment. Urokinase (5000 IU/kg) was delivered bilaterally into the thrombi during 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 ultrasound) (p = 0.058). Angiographically detected distal embolization was found in 2 ultrasound-treated segments compared with 5 controls (p = 0.02). Protruding or occlusive thrombi were seen angioscopically in 8 (89%) control segments but in only 1 (11%) of the ultrasound-treated arteries (p < 0.001). By histopathology, 7 (78%) segments in the control group had occlusive thrombi, whereas only 3 nonocclusive thrombi were found in the ultrasound-treatment group (p < 0.001).


CONCLUSIONS
Catheter-delivered high-frequency ultrasound and local low-dose urokinase infusion is efficacious for the treatment of acute thrombotic occlusions as evaluated by angiography, angioscopy, and histopathology.
Atar
S
S
Division of Cardiology, Cedars-Sinai Medical Center, Los Angeles, California 90048, USA.
Luo
H
H
Nagai
T
T
Sahm
R A
RA
Fishbein
M C
MC
Siegel
R J
RJ
D000818:Animals; D001157:Arterial Occlusive Diseases / Q000000981:diagnostic imaging* / Q000188:drug therapy*; D002408:Catheters, Indwelling; D003131:Combined Modality Therapy; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004617:Embolism / Q000000981:diagnostic imaging; D005263:Femoral Artery / Q000000981:diagnostic imaging / Q000187:drug effects; D015918:Infusion Pumps, Implantable; D023421:Models, Animal; D010960:Plasminogen Activators / Q000494:pharmacology*; D011859:Radiography; D013927:Thrombosis / Q000000981:diagnostic imaging* / Q000188:drug therapy*; D013997:Time Factors; D014159:Transducers; D014464:Ultrasonic Therapy; D014463:Ultrasonography; D014568:Urokinase-Type Plasminogen Activator / Q000008:administration & dosage*; D014654:Vascular Patency / Q000187:drug effects
D010960:Plasminogen Activators; D014568:Urokinase-Type Plasminogen Activator