C K Ryan1, H C Sax. 1. Department of Pathology, University of Rochester Medical Center, New York 14642.
Abstract
BACKGROUND: A novel lyophilized carboxy-methylcellulose (CMC) sponge has been developed for prevention of surgical wound adhesions. One potential mechanism for preventing abdominal adhesion is suppression of the cytokine transforming growth factor beta (TGF-beta) and other macrophage derived fibroblast stimulating factors that partially mediate adhesion formation. METHODS: To study the efficacy and mechanisms of action of the CMC sponge, we performed standard cecal denudation and abdominal wall apposition on rats. A CMC sponge or a commercially available adhesion preventive barrier (Interceed) was placed on the denuded surface. After 14 days, adhesion severity was graded blindly on a scale ranging from 0 (no adhesion) to 5 (severe adhesion). TGF-beta expression was determined by immunocytochemical staining. To assess the secretion of macrophage derived fibrogenic factors in control and CMC rats, labeled thymidine and proline uptake and hydroxyproline production were measured in NRK rat fibroblasts cultured with conditioned medium of peritoneal macrophages. RESULTS: The severity of adhesions in the CMC sponge group (0.7 +/- 0.3) was significantly lower than in the Interceed or control groups (2.2 +/- 0.3; 4.6 +/- 0.1). In control animals TGF-beta expression in endothelium and fibroblasts was maximal on day 3. Neither CMC nor Interceed reduced this expression. Conditioned media derived from sponge-exposed postsurgical peritoneal macrophages did not inhibit fibroblast growth or collagen formation. CONCLUSIONS: In this model the CMC sponge was more effective than Interceed in preventing postoperative adhesions. Its action was not due to inhibition of TGF-beta expression or macrophage derived fibrogenic factors. These data highlight the primary importance of local barrier effect in adhesion prevention.
BACKGROUND: A novel lyophilized carboxy-methylcellulose (CMC) sponge has been developed for prevention of surgical wound adhesions. One potential mechanism for preventing abdominal adhesion is suppression of the cytokine transforming growth factor beta (TGF-beta) and other macrophage derived fibroblast stimulating factors that partially mediate adhesion formation. METHODS: To study the efficacy and mechanisms of action of the CMC sponge, we performed standard cecal denudation and abdominal wall apposition on rats. A CMC sponge or a commercially available adhesion preventive barrier (Interceed) was placed on the denuded surface. After 14 days, adhesion severity was graded blindly on a scale ranging from 0 (no adhesion) to 5 (severe adhesion). TGF-beta expression was determined by immunocytochemical staining. To assess the secretion of macrophage derived fibrogenic factors in control and CMCrats, labeled thymidine and proline uptake and hydroxyproline production were measured in NRK rat fibroblasts cultured with conditioned medium of peritoneal macrophages. RESULTS: The severity of adhesions in the CMC sponge group (0.7 +/- 0.3) was significantly lower than in the Interceed or control groups (2.2 +/- 0.3; 4.6 +/- 0.1). In control animals TGF-beta expression in endothelium and fibroblasts was maximal on day 3. Neither CMC nor Interceed reduced this expression. Conditioned media derived from sponge-exposed postsurgical peritoneal macrophages did not inhibit fibroblast growth or collagen formation. CONCLUSIONS: In this model the CMC sponge was more effective than Interceed in preventing postoperative adhesions. Its action was not due to inhibition of TGF-beta expression or macrophage derived fibrogenic factors. These data highlight the primary importance of local barrier effect in adhesion prevention.