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: C David Mazer, Howard Leong-Poi, Tejinder Chhina, Zuhair Alfardan, Harry Lapierre, Zhilan Wang, Zane S Jackson, Beiping Qiang, James Mahoney, David Latter, Gregory M T Hare, Bradley H Strauss, Jerome Teitel
• Journal: The Journal of thoracic and cardiovascular surgery (J Thorac Cardiovasc Surg) Vol. 142 Issue 2 Pg. 418-23 (Aug 2011) ISSN: 1097-685X [Electronic] United States
• PMID: 21281943 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2010 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

Chemical References

• Recombinant Proteins
• Factor VIIa

Topics

• Anastomosis, Surgical
• Animals
• Carotid Arteries (surgery)
• Dose-Response Relationship, Drug
• Factor VIIa (administration & dosage, adverse effects, pharmacology)
• Graft Occlusion, Vascular (chemically induced)
• Rabbits
• Recombinant Proteins (administration & dosage, adverse effects, pharmacology)
• Thrombosis (chemically induced)
• Vascular Patency (drug effects)