title: Neointimal thickening after severe coronary artery injury is limited by a short-term administration of a factor Xa inhibitor. Results in a porcine model.
abstract: BACKGROUND
  Fibrin- and platelet-rich thrombus formations occur as the initial event after percutaneous transluminal coronary angioplasty. We therefore tested the hypothesis that short-term administration of the recombinant tick anticoagulant peptide (rTAP), a factor Xa inhibitor, would reduce the thickness of neointima at 28 days after injury in a porcine coronary balloon angioplasty model.
  
  
  RESULTS
  Continuous intravenous infusion of rTAP (average dose, 194 micrograms . kg-1 . min-1) or placebo (vehicle only) was given to the study pigs for 60 hours. The goal of anticoagulation was to maintain the activated clotting time at 200 seconds. A central venous catheter was inserted 2 days before the procedure. On the day of coronary injury, the animals were administered boluses of rTAP (6.5 mg) and then underwent injury with an oversized metallic coil by standard methods in the right, circumflex, or left anterior descending coronary artery. No significant difference in vascular injury between rTAP and vehicle control was observed after euthanasia at 28 days. Significantly less neointimal thickening occurred in the rTAP-treated animals (thickness, mean +/-SD: 0.30 +/-0.08 mm) compared with the control (0.48 +/- 0.12 mm, P< .001).
  
  
  CONCLUSIONS
  The specific factor Xa inhibitor rTAP, when given in fully anticoagulant doses for a short duration after coronary artery injury in the porcine model, resulted in a long-term decrease in neointimal thickness. These results implicate thrombin generation in neointimal formation and suggest that administration of a potent antithrombotic for several days immediately after the procedure may influence the long-term outcome of the coronary injury with a decrease in neointimal formation.
authors.affiliation: Division of Cardiovascular Diseases and Internal Medicine, Mayo Clinic and Foundation, Rochester, Minnesota 55905, USA.
authors.forename: R S
authors.initials: RS
authors.lastname: Schwartz
authors.forename: D J
authors.initials: DJ
authors.lastname: Holder
authors.forename: D R
authors.initials: DR
authors.lastname: Holmes
authors.forename: J P
authors.initials: JP
authors.lastname: Veinot
authors.forename: A R
authors.initials: AR
authors.lastname: Camrud
authors.forename: M A
authors.initials: MA
authors.lastname: Jorgenson
authors.forename: R G
authors.initials: RG
authors.lastname: Johnson
mesh_terms: D015906:Angioplasty, Balloon, Coronary / Q000009:adverse effects*; D000818:Animals; D060829:Arthropod Proteins; D001777:Blood Coagulation / Q000187:drug effects; D003331:Coronary Vessels / Q000293:injuries* / Q000473:pathology; D065427:Factor Xa Inhibitors; D036341:Intercellular Signaling Peptides and Proteins; D010314:Partial Thromboplastin Time; D010455:Peptides / Q000627:therapeutic use*; D011994:Recombinant Proteins; D015842:Serine Proteinase Inhibitors / Q000627:therapeutic use*; D013552:Swine
chemical_list: D060829:Arthropod Proteins; D065427:Factor Xa Inhibitors; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; D011994:Recombinant Proteins; D015842:Serine Proteinase Inhibitors; C063967:tick anticoagulant peptide