Animal Model for Local Pharmacotherapy in Adhesion Prophylaxis—A Proof of Concept

ABSTRACT

Background: On the one hand, barrier materials remain the only licensed adjuncts for postoperative adhesion reduction in the United States. On the other hand, pharmacotherapy for adhesion reduction has been a focus of intensive research. Therefore, the next step in the evolution of adhesion prophylaxis will consist of pharmacological functionalization of barrier materials to locally elute drugs. However, conventionally available animal models for postoperative adhesions are not optimized to screen candidate pharmaceutical agents for their local adhesion suppressing properties. Therefore, we have developed an animal model specifically for this purpose. Methods: Ischemic peritoneal lesions are created by ligating buttons of transversus abdominis muscle with sutures. These ischemic lesions are then directly injected with the candidate pharmaceutical agent. Injection of ischemic tissue ensures that the tested agent can only exert a local effect. Lesions injected with normal saline serve as internal controls. Results: In a pilot experiment n = 40 lesions were created in 10 Wistar rats and injected with normal saline. When analyzed by interval laparotomy on postoperative day 10, 58% (n = 23/40) of these lesions were affected by adhesions (95% confidence interval 42–71%). None of the adhesions were avascular. Ten adhesions were filmy and vascular. Twelve adhesions were dense and vascular. One adhesion involved organ inclusion with the liver attached to the experimental lesions. Conclusion: The described model is suitable for screening pharmaceutical agents for their local adhesion suppressing properties. It will help with the development of novel adhesion barriers that simultaneously function as drug-eluting vehicles.

Keywords: :

• adhesions
• rat
• model
• local effect
• pharmaceuticals