title: Recombinant factor VIIa affects anastomotic patency of vascular grafts in a rabbit model.
abstract: OBJECTIVE
  Recombinant factor VIIa can decrease postoperative bleeding after cardiac surgery. However, the potential for recombinant factor VIIa to cause early vascular graft occlusion at the site of new vascular anastomoses has not been fully explored. We hypothesized that recombinant factor VIIa would cause a dose-dependent reduction in vascular graft patency in rabbits.
  
  
  METHODS
  Reversed end-to-end interpositional vein grafts were sutured into the carotid artery of heparinized rabbits, and then recombinant factor VIIa (300 μg/kg, 90 μg/kg, or 20 μg/kg intravenously) or placebo was administered (n = 16/group). Graft patency was assessed at 24 hours using a vascular ultrasound probe. Factor VII activity levels were measured using a prothrombin time-based assay. In different rabbits, the patency of venous end-to-side anastomoses and simple carotid arterial repairs was assessed (recombinant factor VIIa, 300 μg/kg vs placebo, n = 8/group). Data were analyzed using Fisher's exact test, t tests, or analysis of variance.
  
  
  RESULTS
  Physiologic variables (activated clotting time, hemoglobin, pH, Pao(2)) and vessel diameter were not different between groups. Vein graft patency was reduced (93.8%, 81.2%, 13.8%, and 6.3%) as factor VII activity levels increased (1.8 ± 0.4, 4.4 ± 2.1, 11.8 ± 4.7, and 23.6 ± 16.9 U/mL, respectively) with increasing doses of recombinant factor VIIa administered (0, 20, 90, and 300 μg/kg, respectively, P < .05). Patency in the arterial repairs and end-to-side venous grafts was also reduced in recombinant factor VIIa-treated rabbits (P < .05 for both).
  
  
  CONCLUSIONS
  This study suggests that recombinant factor VIIa is associated with a dose-dependent increase in fresh vascular graft occlusion. Higher doses of recombinant factor VIIa may be associated with increased thrombotic outcomes.
authors.affiliation: Department of Anesthesia, University of Toronto, Toronto, Ontario, Canada. mazerd@smh.ca
authors.forename: C David
authors.initials: CD
authors.lastname: Mazer
authors.forename: Howard
authors.initials: H
authors.lastname: Leong-Poi
authors.forename: Tejinder
authors.initials: T
authors.lastname: Chhina
authors.forename: Zuhair
authors.initials: Z
authors.lastname: Alfardan
authors.forename: Harry
authors.initials: H
authors.lastname: Lapierre
authors.forename: Zhilan
authors.initials: Z
authors.lastname: Wang
authors.forename: Zane S
authors.initials: ZS
authors.lastname: Jackson
authors.forename: Beiping
authors.initials: B
authors.lastname: Qiang
authors.forename: James
authors.initials: J
authors.lastname: Mahoney
authors.forename: David
authors.initials: D
authors.lastname: Latter
authors.forename: Gregory M T
authors.initials: GM
authors.lastname: Hare
authors.forename: Bradley H
authors.initials: BH
authors.lastname: Strauss
authors.forename: Jerome
authors.initials: J
authors.lastname: Teitel
mesh_terms: D000714:Anastomosis, Surgical; D000818:Animals; D002339:Carotid Arteries / Q000601:surgery; D004305:Dose-Response Relationship, Drug; D015942:Factor VIIa / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D006083:Graft Occlusion, Vascular / Q000139:chemically induced; D011817:Rabbits; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D013927:Thrombosis / Q000139:chemically induced; D014654:Vascular Patency / Q000187:drug effects*
chemical_list: D011994:Recombinant Proteins; D015942:Factor VIIa