Intraperitoneal Administration Of Activated Protein C Prevents Post-Surgical Adhesion Band Formation

Postoperative intraperitoneal adhesion bands are the most important causes of intestinal obstruction, pelvic pain and female infertility. Adhesion bands are induced by inflammatory responses elicited by injury following surgery. The objective of this study was to evaluate the effectiveness of activated protein C (APC), a natural anticoagulant and antiinflammatory serine protease in plasma, in preventing post-surgical intraperitoneal adhesion band formation. The protective effects of APC and the FDA approved agent, sodium hyaluronate/carboxymethylcellulose (HA/CMC, also called Seprafilm), were compared by administering the two drugs intraperitoneally into 30 male C57bl/6 mice. After 7 days, the pathological adhesion grades were scored by two scaling systems and the peritoneal fluid concentration of tissue plasminogen activator (tPA) as well as the concentrations of the proinflammatory cytokines, IL-1, IL-6, TNF-α, IFN-γ and TGF-β were evaluated. The inflammation scores of mice in all groups were also measured based on histological data obtained from peritoneal tissues. Relative to the HA/CMC group, intraperitoneal administration of APC led to a significantly higher reduction of adhesion band formation. Moreover, a markedly lower inflammation score was obtained in the adhesive tissues of the APC-treated group which correlated with significantly reduced peritoneal concentrations of IL-6, TNF-α, IFN-γ and TGF-β and elevated concentration of tPA in this group. These results suggest that in comparison to the FDA approved agent, Seprafilm, APC exhibits a markedly higher efficacy in preventing postoperative adhesion band formation. Thus, APC holds the potential to be therapeutically used as a novel anti-adhesive agent.