title: Pulsed high-intensity-focused US and tissue plasminogen activator (TPA) versus TPA alone for thrombolysis of occluded bypass graft in swine.
abstract: OBJECTIVE
  Prosthetic arteriovenous or arterial-arterial bypass grafts can thrombose and be resistant to revascularization. A thrombosed bypass graft model was created to evaluate the potential therapeutic enhancement and safety profile of pulsed high-intensity-focused ultrasound (pHIFU) on pharmaceutical thrombolysis.
  
  
  METHODS
  In swine, a right carotid-carotid expanded polytetrafluoroethylene bypass graft was surgically constructed, containing a 40% stenosis at its distal end to induce graft thrombosis. The revascularization procedure was performed 7 days after surgery. After model development and dose response experiments (n = 11), two cohorts were studied: pHIFU with tissue plasminogen activator (TPA; n = 4) and sham pHIFU with TPA (n = 3). The experiments were identical in both groups except no energy was delivered in the sham pHIFU group. Serial angiograms were obtained in all cases. The area of graft opacified by contrast medium on angiograms was quantified with digital image processing software. A blinded reviewer calculated the change in the graft area opacified by contrast medium and expressed it as a percentage, representing percentage of thrombolysis.
  
  
  RESULTS
  Combining pHIFU with 0.5 mg of TPA resulted in a 52% ± 4% increase in thrombolysis on angiograms obtained at 30 minutes, compared with a 9% ± 14% increase with sham pHIFU and 0.5 mg TPA (P = .003). Histopathologic examination demonstrated no differences between the groups.
  
  
  CONCLUSIONS
  Thrombolysis of occluded bypass grafts was significantly increased when combining pHIFU and TPA versus sham pHIFU and TPA. These results suggest that application of pHIFU may augment thrombolysis with a reduced time and dose.
authors.affiliation: Department of Radiology and Imaging Sciences, National Institutes of Health, Bethesda, MD 20892, USA. naj@mail.nih.gov
authors.forename: Nadine
authors.initials: N
authors.lastname: Abi-Jaoudeh
authors.forename: William F
authors.initials: WF
authors.lastname: Pritchard
authors.forename: Hayet
authors.initials: H
authors.lastname: Amalou
authors.forename: Marius
authors.initials: M
authors.lastname: Linguraru
authors.forename: Oscar A
authors.initials: OA
authors.lastname: Chiesa
authors.forename: Joshua D
authors.initials: JD
authors.lastname: Adams
authors.forename: Carmen
authors.initials: C
authors.lastname: Gacchina
authors.forename: Robert
authors.initials: R
authors.lastname: Wesley
authors.forename: Subha
authors.initials: S
authors.lastname: Maruvada
authors.forename: Briana
authors.initials: B
authors.lastname: McDowell
authors.forename: Victor
authors.initials: V
authors.lastname: Frenkel
authors.forename: John W
authors.initials: JW
authors.lastname: Karanian
authors.forename: Bradford J
authors.initials: BJ
authors.lastname: Wood
mesh_terms: D000818:Animals; D003131:Combined Modality Therapy; D057086:High-Intensity Focused Ultrasound Ablation; D013552:Swine; D015912:Thrombolytic Therapy; D013927:Thrombosis / Q000209:etiology* / Q000628:therapy*; D010959:Tissue Plasminogen Activator; D016896:Treatment Outcome; D058017:Vascular Grafting / Q000009:adverse effects*
chemical_list: D010959:Tissue Plasminogen Activator