International Anesthesia Research Society

Erik B. Kistler, Xiaodong Zhang, Jun Tang, Fernando dos Santos

Abstract

Introduction:
Postoperative abdominal adhesions are a common sequela following abdominal surgery, often leading to chronic pain, bowel obstruction, and further surgical interventions. Preventing these adhesions is thus a significant goal in surgical practice. However, no effective pharmacological interventions are currently available, and the mechanisms by which these adhesions are formed are incompletely understood. Aberrant plasmin activity has been implicated in the pathogenesis of abdominal adhesions, and enteral infusion of the plasminogen inhibitor, tranexamic acid (TXA), was recently reported to have some efficacy in a clinical trial. However, results were not clinically significant. Two new compounds, BT-114143 and BT-114043, with enhanced plasmin-inhibitor profiles, have recently been developed with the aim of offering enhanced performance in adhesion prevention, potentially minimizing side effects and improving patient outcomes.

Aim:
This study aimed to establish a reproducible clinically relevant model of surgically-mediated abdominal adhesions and evaluate and compare the efficacy of experimental drugs BT-114143 and BT-114043 to TXA given enterally for the prevention of postoperative abdominal adhesions.

Methods:
Abdominal adhesion formation was induced in an anesthetized rat model (n = 10/group) using standardized surgical techniques, with abrasion of the stomach, duodenum, ileum, and cecum using a swab coated with a latex glove. Except for the SHAM group (laparotomy only), animals were randomized to receive enteral treatment with TXA (1 g/kg), BT-114043 (0.35 g/kg), BT-114143 (0.4 g/kg), or vehicle. Efficacy was assessed 15 days after intervention based on adhesion severity and incidence. All procedures were approved by the University Institutional Animal Care and Use Committee.

Results:
From the four possible adhesion sites, BT-114043 demonstrated significantly greater efficacy in preventing adhesion formation (1.70 ± 0.26, p < 0.01) compared to Vehicle (3.10 ± 0.31) and TXA (2.70 ± 0.33). BT-114143 showed an average number of adhesion sites of 2.30 ± 0.30, while the SHAM group had 0.20 ± 0.13. Both BT-114043 (0.65 ± 0.09) and BT-114143 (0.90 ± 0.11) resulted in a lower adhesion severity score (from 0 to 3) compared to the Vehicle (1.60 ± 0.20, p < 0.01) and TXA (1.23 ± 0.16, p < 0.05) groups, with the most profound effects observed in animals treated with BT-114043.

Conclusions:
These results suggest that enteral treatment with plasminogen inhibitors, specifically BT-114043, may be a viable therapeutic option for the prevention of abdominal adhesions post-surgery.

“© 2025 [Scinnohub]. Originally presented at IARS 2025.”