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Original research
A thromboembolic model for the efficacy and safety evaluation of combined mechanical and pharmacologic revascularization strategies
  1. Matthew J Gounis1,
  2. Raul G Nogueira2,
  3. Manik Mehra1,
  4. Juyu Chueh1,
  5. Ajay K Wakhloo1
  1. 1Department of Radiology, New England Center for Stroke Research, University of Massachusetts Medical School, Worcester, Massachusetts, USA
  2. 2Marcus Stroke & Neuroscience Center, Grady Memorial Hospital, Department of Neurology, Neurosurgery, and Radiology, Emory University, Atlanta, Georgia, USA
  1. Correspondence to Dr M J Gounis, Department of Radiology, New England Center for Stroke Research, University of Massachusetts, 55 Lake Avenue North, SA-107R, Worcester, MA 01655, USA; matt.gounis{at}umassmed.edu

Abstract

Background and purpose 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.

  • Stroke
  • Technology
  • Thrombectomy
  • Thrombolysis
  • Vessel Wall

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