Comparison of Antiadhesive Treatments using an Objective Rat Model

Abstract

Intraperitoneal adhesions are a significant problem (increased morbidity, mortality, and cost) for patients undergoing abdominal procedures. Although a variety of approaches (e.g., fibrinolytic agents, anti-inflammatory drugs, or barrier/separation methods) have been used with some success in preventing adhesions, a comparison of these different modalities has yet to be performed in a model that objectively measures intraperitoneal adhesion formation. Our objectives were to establish an objective, reproducible model of intraperitoneal adhesion formation and to establish efficacy of different treatment modalities in decreasing the strength and extent of intraperitoneal adhesions. In this two-part study, a rat model establishing an objective measure of both the strength and extent of intraperitoneal adhesions was used to compare different treatment modalities. Fibrinolytic agents [recombinant tissue plasminogen activator (rtPA), streptokinase, and urokinase], anti-inflammatory drugs (dexamethasone and tolmetin sodium), and barrier methods [sodium carboxymethylcellulose (CMC), and sodium hyaluronate] and a control group were compared in the first phase. In the second phase, the two most successful agents (rtPA, CMC) were compared both alone and in combination against a commercially available barrier agent (Seprafilm) and a control group. In the first phase of the study, rtPA was the only agent that had a statistically significant effect in decreasing the strength of adhesions. CMC was the only agent that demonstrated a decrease in the extent of adhesions, and the difference tended toward significance. In the second phase, the combination of rtPA and CMC showed a significant decrease in both the strength and extent of adhesions when compared with those of the control group. This decrease was also observed in the group treated with Seprafilm, which showed no difference from the rtPA + CMC group. We conclude that, in this reproducible adhesion model, only the combination of rtPA + CMC and Seprafilm significantly reduced both the strength and the extent of intraperitoneal adhesions.