title: Noninvasive transcutaneous low frequency ultrasound enhances thrombolysis in peripheral and coronary arteries.
abstract: Previous studies have shown that external ultrasound with low frequencies and high intensities can enhance thrombolytic drug-induced clot dissolution during in vitro experiments. In this series of studies, we evaluated the efficacy of peripheral and coronary thrombolysis in vivo in animals by using noninvasive transcutaneous ultrasound combined with thrombolytic drugs (streptokinase and tPA) and/or microbubbles agents (dodecafluoropentane [DDFP] and perfluorocarbon-exposed sonicated dextrose albumin [PESDA]). Thrombotic occlusions were induced in 74 rabbit iliofemoral arteries and 24 canine left anterior descending (LAD) coronary arteries in this in vivo study. By using the combination of transcutaneous ultrasound and streptokinase, the angiographic patency rate in rabbit iliofemoral arteries was higher (56%-100%) than with ultrasound (6%; P < or = 0.0036) and streptokinase alone (6%; P < or = 0.0012). Also, with transcutaneous ultrasound and microbubbles, the angiographic patency rates were 76%-100% as compared with ultrasound alone (0%, P < or = 0.0003) or microbubbles alone (9%, P < or = 0.0001). In the canine study of acute myocardial infarction, thrombolysis in myocardial infarction (TIMI) grade flow at 90 minutes in the tPA alone group was 0.92 +/- 1.4 as compared with 2.42 +/- 1.9 in the tPA plus transthoracic ultrasound group (P = 0.006). There was much improved reperfusion with tPA plus ultrasound as compared with tPA alone. In vivo animal studies demonstrate that noninvasive transcutaneous ultrasound can greatly enhance the effect of clot dissolution with thrombolytic drugs and/or microbubbles, and has the potential for clinical application as an adjunctive method to improve arterial thrombolysis.
authors.affiliation: Division of Cardiology, Department of Medicine, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, CA 90048, USA. siegel@cshs.org
authors.forename: R J
authors.initials: RJ
authors.lastname: Siegel
authors.forename: S
authors.initials: S
authors.lastname: Atar
authors.forename: M C
authors.initials: MC
authors.lastname: Fishbein
authors.forename: A V
authors.initials: AV
authors.lastname: Brasch
authors.forename: T M
authors.initials: TM
authors.lastname: Peterson
authors.forename: T
authors.initials: T
authors.lastname: Nagai
authors.forename: D
authors.initials: D
authors.lastname: Pal
authors.forename: T
authors.initials: T
authors.lastname: Nishioka
authors.forename: J S
authors.initials: JS
authors.lastname: Chae
authors.forename: Y
authors.initials: Y
authors.lastname: Birnbaum
authors.forename: C
authors.initials: C
authors.lastname: Zanelli
authors.forename: H
authors.initials: H
authors.lastname: Luo
mesh_terms: D000818:Animals; D003328:Coronary Thrombosis / Q000628:therapy*; D005343:Fibrinolytic Agents / Q000627:therapeutic use; D013300:Streptokinase / Q000627:therapeutic use; D015912:Thrombolytic Therapy / Q000379:methods*; D013927:Thrombosis / Q000628:therapy*; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use; D014464:Ultrasonic Therapy
chemical_list: D005343:Fibrinolytic Agents; D013300:Streptokinase; D010959:Tissue Plasminogen Activator