Enhancement of Thrombolysis In Vivo Without Skin and Soft Tissue Damage by Transcutaneous Ultrasound

Previous studies have shown that transcutaneous ultrasound enhances thrombolysis by streptokinase in animals in vivo; however, skin and soft tissue damage induced by ultrasound energy has been a major limitation. The objective of this study was to examine the efficacy of thrombolysis and damage to skin and soft tissues using a newly designed concentrated ultrasound system with a cooling manifold. Using a rabbit model with iliofemoral arterial thrombotic occlusions, 15 pairs of arteries were randomized to receive ultrasound treatment or no ultrasound treatment. Streptokinase (25,000 unit/kg) was given intravenously. Skin temperature was maintained at 25–33°C when ultrasound energy was applied. The serum level of creatine kinase, lactate dehydrogenase, red blood cell counts, and platelet counts were checked at baseline, after thrombus induction, and after ultrasound treatment. Fifteen of fifteen (100%) iliofemoral arteries were angiographically recanalized after ultrasound treatment. In contrast, only 1/15 (6.7%) contralateral arteries were patent after 1 hour. After the subsequent hour with heparin the patency was 14/15 in the ultrasound treated group and 3/15 in the control group. Histologically, the patent arteries had only minimal focal mural thrombus, whereas the angiographically occluded arteries had occlusive thrombi. There was no histologic evidence of ultrasound induced damage to overlying skin, soft tissues, or arteries. In addition, there was no significant rise of creatine kinase, lactate dehydrogenase, or decrease in red blood cell counts and platelet counts induced by ultrasound. In conclusion, transcutaneous concentrated ultrasound which significantly enhances streptokinase induced thrombolysis in vivo can be delivered without concomitant tissue damage. This simple combination therapy has clinical potential for safely treating patients with arterial or venous thromboses.