title: An optimized method to assess in vivo efficacy of antithrombotic drugs using optical coherence tomography and a modified Doppler flow system.
abstract: BACKGROUND
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: In Vivo Pharmacology Department, Biotechnology Research Institute, National Research Council Canada, Montreal, Quebec, Canada, H4P 2R2.
authors.forename: L
authors.initials: L
authors.lastname: Couture
authors.forename: L P
authors.initials: LP
authors.lastname: Richer
authors.forename: C
authors.initials: C
authors.lastname: Cadieux
authors.forename: C M
authors.initials: CM
authors.lastname: Thomson
authors.forename: S M
authors.initials: SM
authors.lastname: Hossain
mesh_terms: D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D006493:Heparin / Q000494:pharmacology; D006629:Hirudins / Q000494:pharmacology; D017078:Laser-Doppler Flowmetry / Q000379:methods*; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology; D010875:Pipecolic Acids / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology; D012079:Renal Circulation / Q000187:drug effects; D013449:Sulfonamides; D013927:Thrombosis / Q000188:drug therapy; D041623:Tomography, Optical Coherence / Q000379:methods*
chemical_list: D005343:Fibrinolytic Agents; D006629:Hirudins; D010446:Peptide Fragments; D010875:Pipecolic Acids; D011994:Recombinant Proteins; D013449:Sulfonamides; D006493:Heparin; D001120:Arginine; C031942:argatroban; C074619:bivalirudin