title: Effect of acoustic conditions on microbubble-mediated microvascular sonothrombolysis.
abstract: Ultrasound (US) mediated microbubble (MB) destruction facilitates thrombolysis of the epicardial coronary artery in acute myocardial infarction (AMI) but its effect on microvascular thromboemboli remains largely unexplored. We sought to define the acoustic requirements for effective microvascular sonothrombolysis. To model microembolization, microthrombi were injected and entrapped in a 40 μm pore mesh, increasing upstream pressure, which was measured as an index of thrombus burden. MBs (2.0 × 10(6) MBs/mL) were then infused while pulsed US (1 MHz) was delivered to induce MB destruction immediately adjacent to the thrombus. Upstream pressure decreased progressively during US delivery, indicating a reduction in thrombus burden. More rapid and complete lysis occurred with increasing peak negative acoustic pressure (1.5 MPa > 0.6 MPa) and increasing pulse length (5000 cycles > 100 cycles). Additionally, similar lytic efficacy was achieved at 1.5 MPa without tPA as was at 1.0 MPa with tPA. This model uniquely provides a means to systematically evaluate multiple acoustic and microbubble parameters for the optimization of microvascular sonothrombolysis. This treatment approach for thrombotic microvascular obstruction may obviate the need for adjunctive rt-PA and could have important clinical cost and safety benefits.
authors: Center for Ultrasound Molecular Imaging and Therapeutics, University of Pittsburgh Medical Center, Heart and Vascular Institute, Pittsburgh, PA, USA.
authors: Jonathan E
authors: JE
authors: Leeman
authors: Jong S
authors: JS
authors: Kim
authors: Francois T H
authors: FT
authors: Yu
authors: Xucai
authors: X
authors: Chen
authors: Kang
authors: K
authors: Kim
authors: Jianjun
authors: J
authors: Wang
authors: Xianghui
authors: X
authors: Chen
authors: Flordeliza S
authors: FS
authors: Villanueva
authors: John J
authors: JJ
authors: Pacella
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D003287:Contrast Media / Q000494:pharmacology; D004867:Equipment Design; D005343:Fibrinolytic Agents / Q000494:pharmacology; D066298:In Vitro Techniques; D045423:Microbubbles; D009203:Myocardial Infarction / Q000628:therapy*; D013552:Swine; D013923:Thromboembolism / Q000628:therapy*; D015912:Thrombolytic Therapy / Q000295:instrumentation / Q000379:methods*; D010959:Tissue Plasminogen Activator / Q000494:pharmacology; D041623:Tomography, Optical Coherence; D014464:Ultrasonic Therapy / Q000295:instrumentation / Q000379:methods*
chemical_list: D003287:Contrast Media; D005343:Fibrinolytic Agents; D010959:Tissue Plasminogen Activator