AK03, a new recombinant fibrinogenase prevents abdominal adhesions in a rat model without systemic side effects

Background: Abdominal adhesions are one of the most common complications after abdominal surgery, and fibrin is suspected to be a crucial component. The aim of the current study was an in vivo evaluation of a new recombinant fibrinogenase (AK03) in two animal models.

Methods: Sixty-four rats were randomly divided into four groups (sodium chloride [NaCl], icodextrin, AK03 low dose, and AK03 high dose) and evaluated at two time endpoints. Adhesion model comprised both a visceral defect (terminal ileum) and parietal defect. Test (AK03) and control substances (NaCl and icodextrin) were administered intraperitoneally after setting the intraabdominal defects. A second dose was administered 24 h after surgery. Plasma fibrinogen values were taken at baseline and after 7 and 21 d, respectively. Rats were sacrificed after 7 or 21 d for macroscopic (Diamond score) and immunohistochemical investigations.

Results: After 7 and 21 d, the Diamond score of postsurgical adhesions were significantly lower in both AK03-treated groups compared with NaCl control group (P = 0.02). There were no unspecific systemic side effects in both treatment groups and no decrease in plasma fibrinogen concentration. In none of the four groups was there any evidence for impaired wound repair. Microscopically in the area of the parietal defect, we saw less cluster of differentiation 3(+) T-lymphocytes and cluster of differentiation 68(+) macrophages in both groups receiving AK03 compared with the NaCl and icodextrin control groups.

Conclusions: The results of this study indicate that the new recombinant fibrinogenase AK03 effectively prevents peritoneal adhesions without causing side effects, notably systemic fibrinogen depletion, bleeding, or impaired wound repair. Due to these results, future clinical studies may be promising. (C) 2017 Elsevier Inc. All rights reserved.