title: A thromboembolic model for the efficacy and safety evaluation of combined mechanical and pharmacologic revascularization strategies.
abstract: OBJECTIVE
  Recanalization strategies mediated by intra-arterial fibrinolytic therapy in combination with mechanical clot disruption may be a more effective treatment approach than either therapy used alone. There are few preclinical animal models to evaluate these strategies. Here we report on a model to simultaneously evaluate both of these treatment approaches.
  
  
  METHODS
  Allogeneic clot was injected through the 6 F guide catheter after creating >50% luminal stenosis of the common carotid arteries of New Zealand White rabbits. The stenosis was released after 1 h, allowing sufficient time for clot-vessel wall interaction. Occlusion was confirmed and each vessel was assigned to receive either balloon angioplasty alone, intra-arterial tissue plasminogen activator (tPA, Alteplase, Genentech, San Francisco, California, USA), tPA delivery through prototype balloon infusion wire (NIT Therapeutics, Pittsburgh, Pennsylvania, USA), partial stent deployment or partial stent deployment with locally delivered tPA. The negative control received no treatment.
  
  
  RESULTS
  In vivo revascularization Thrombolysis in Cerebral Infarction (TICI) score revealed that the balloon infusion wire achieved a stable and higher revascularization score of TICI 2B, with a lower dose of tPA in comparison with other treatment strategies. All treatment strategies resulted in endothelial denudation and exposure of the internal elastic lamina.
  
  
  CONCLUSIONS
  The proposed animal model permits reliable and consistent thromboembolic occlusion of the target vasculature and allows for an assessment of both pharmacologic and mechanical revascularization strategies for acute ischemic stroke.
authors.affiliation: Department of Radiology, New England Center for Stroke Research, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA. matt.gounis@umassmed.edu
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Gounis
authors.forename: Raul G
authors.initials: RG
authors.lastname: Nogueira
authors.forename: Manik
authors.initials: M
authors.lastname: Mehra
authors.forename: Juyu
authors.initials: J
authors.lastname: Chueh
authors.forename: Ajay K
authors.initials: AK
authors.lastname: Wakhloo
mesh_terms: D000818:Animals; D002548:Cerebral Revascularization / Q000009:adverse effects / Q000379:methods*; D003131:Combined Modality Therapy / Q000009:adverse effects / Q000379:methods; D004195:Disease Models, Animal; D008297:Male; D061185:Mechanical Thrombolysis / Q000009:adverse effects / Q000379:methods*; D011817:Rabbits; D011859:Radiography; D013923:Thromboembolism / Q000000981:diagnostic imaging / Q000628:therapy*; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D010959:Tissue Plasminogen Activator