An optimized method to assess in vivo efficacy of antithrombotic drugs using optical coherence tomography and a modified Doppler flow system

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DOIResolve DOI: http://doi.org/10.1016/j.vascn.2011.09.001
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TypeArticle
Journal titleJournal of Pharmacological and Toxicological Methods
ISSN1056-8719
Volume64
Issue3
Pages264268; # of pages: 5
Subjectargatroban; heparin; hirulog; animal experiment; animal model; animal tissue; artery thrombosis; article; blood flowmetry; controlled study; Doppler flowmetry; drug efficacy; in vivo study; male; nonhuman; optical coherence tomography; process optimization; rat; thrombogenesis; vein thrombosis; Animals; Drug Evaluation, Preclinical; Fibrinolytic Agents; Heparin; Hirudins; Laser-Doppler Flowmetry; Male; Peptide Fragments; Pipecolic Acids; Rats; Rats, Sprague-Dawley; Recombinant Proteins; Renal Circulation; Thrombosis; Tomography, Optical Coherence; Animalia; Rattus
AbstractIntroduction: Animal models of venous and arterial thrombosis are extremely useful to study the efficacy of antithrombotic agents. Variability in efficacy data is often observed in those preclinical studies. The goal of this study was to optimize the methodology for assessing antithrombotic drug efficacy by the use of optical coherence tomography (OCT) and a modified Doppler flow system in rat models of thrombosis. Methods: Thrombus formation was assessed in both the rat venous and arterial ferric chloride (FeCl 3) models of thrombosis. In the venous model, thrombus volume post-treatment was measured using OCT, and data were correlated against the thrombus weight. In the arterial model, the time to occlusion was measured using a Doppler flow probe connected to a perivascular flow module which allowed the reporting of dynamic blood flow data every 30s. Heparin (130 or 165U/kg), argatroban (4.5mg/kg), bivalirudin (1.3mg/kg) or saline were administered intravenously. Results: In the venous model, for all treatment groups a strong linear correlation (R 2=0.998) was observed between thrombus volume measured by OCT and thrombus weight. In the arterial model, using a high sampling rate of a dynamic blood flow using a modified Doppler flow system provided data accuracy and precision of the time to occlusion measurement. Discussion: This study demonstrates that OCT is a powerful tool for the assessment of antithrombotic drug efficacy. Furthermore, it shows that a high Doppler sampling rates of dynamic blood flow leads to data accuracy and precision. © 2011.
Publication date
LanguageEnglish
AffiliationNational Research Council Canada (NRC-CNRC); NRC Biotechnology Research Institute (BRI-IRB)
Peer reviewedYes
NPARC number21271091
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Record identifier080333cf-9258-43b9-9bdd-0f15b473afb6
Record created2014-03-24
Record modified2016-05-09
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