title: Effect of Thrombus Composition and Viscosity on Sonoreperfusion Efficacy in a Model of Micro-Vascular Obstruction.
abstract: Distal embolization of micro-thrombi during stenting for myocardial infarction causes micro-vascular obstruction (MVO). We have previously shown that sonoreperfusion (SRP), a microbubble (MB)-mediated ultrasound (US) therapy, resolves MVO from venous micro-thrombi in vitro in saline. However, blood is more viscous than saline, and arterial thrombi that embolize during stenting are mechanically distinct from venous clot. Therefore, we tested the hypothesis that MVO created with arterial micro-thrombi are more resistant to SRP therapy compared with venous micro-thrombi, and higher viscosity further increases the US requirement for effective SRP in an in vitro model of MVO. Lipid MBs suspended in plasma with adjusted viscosity (1.1 cP or 4.0 cP) were passed through tubing bearing a mesh with 40-μm pores to simulate a micro-vascular cross-section; upstream pressure reflected thrombus burden. To simulate MVO, the mesh was occluded with either arterial or venous micro-thrombi to increase upstream pressure to 40 mmHg ± 5 mmHg. Therapeutic long-tone-burst US was delivered to the occluded area for 20 min. MB activity was recorded with a passive cavitation detector. MVO caused by arterial micro-thrombi at either blood or plasma viscosity resulted in less effective SRP therapy compared to venous thrombi. Higher viscosity further reduced the effectiveness of SRP therapy. The passive cavitation detector showed a decrease in inertial cavitation when viscosity was increased, while stable cavitation was affected in a more complex manner. Overall, these data suggest that arterial thrombi may require higher acoustic pressure US than venous thrombi to achieve similar SRP efficacy; increased viscosity decreases SRP efficacy; and both inertial and stable cavitation are implicated in observed SRP efficacy.
authors.affiliation: Center for Ultrasound Molecular Imaging and Therapeutics, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
authors.forename: John J
authors.initials: JJ
authors.lastname: Black
authors.affiliation: Center for Ultrasound Molecular Imaging and Therapeutics, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
authors.forename: Francois T H
authors.initials: FT
authors.lastname: Yu
authors.affiliation: Center for Ultrasound Molecular Imaging and Therapeutics, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
authors.forename: Rick G
authors.initials: RG
authors.lastname: Schnatz
authors.affiliation: Center for Ultrasound Molecular Imaging and Therapeutics, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
authors.forename: Xucai
authors.initials: X
authors.lastname: Chen
authors.affiliation: Center for Ultrasound Molecular Imaging and Therapeutics, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
authors.forename: Flordeliza S
authors.initials: FS
authors.lastname: Villanueva
authors.affiliation: Center for Ultrasound Molecular Imaging and Therapeutics, University of Pittsburgh Medical Center, Pittsburgh, PA, USA. Electronic address: pacellajj@upmc.edu.
authors.forename: John J
authors.initials: JJ
authors.lastname: Pacella
mesh_terms: D001157:Arterial Occlusive Diseases / Q000628:therapy*; D066298:In Vitro Techniques; D045423:Microbubbles; D055806:Microvessels / Q000503:physiopathology*; D013927:Thrombosis / Q000503:physiopathology* / Q000628:therapy*; D016896:Treatment Outcome; D014464:Ultrasonic Therapy / Q000379:methods*; D014465:Ultrasonics; D014783:Viscosity
keywords: Micro-vascular obstruction; Microbubbles; Sonoreperfusion; Thrombolysis; Ultrasound