Role of Activated Protein C on Wound Healing Process in Left Colonic Anastomoses in the Presence of Intra‐abdominal Sepsis Induced by Cecal Ligation and Puncture: An Experimental Study in the Rat

Abstract

Activated protein C (APC) is a serine protease with anticoagulant and anti-inflammatory activities. The delaying effects of intra-abdominal sepsis on wound healing process in colonic anastomoses have been previously demonstrated. This study was designed to investigate the role of APC on wound healing process in left colonic anastomoses in the presence of intra-abdominal sepsis. The left colonic anastomosis was performed in 48 rats that were divided into four groups: (1) sham-operated group, laparatomy plus cecal mobilization (n = 12); (2) sham + APC group, identical to group I except for APC treatment (n = 12); (3) CLP group, cecal ligation and puncture (n = 12); 4) CLP + APC-treated group, 100 microg/kg, 15 min before the construction of colonic anastomosis (n = 12). Anastomotic bursting pressures were measured in vivo on day 7. Tissue samples were obtained for analyses of hydroxyproline (HP) contents, myeloperoxidase (MPO) acivity, malondialdehyde (MDA), and nitrate/nitrite (NO3(-) /NO2(-)) levels. The plasma levels of tumor necrosis factor alpha (TNF-alpha), interleukin (IL)-6, and D-dimer also were measured. Intra-abdominal sepsis led to significant decreases in colonic anastomotic bursting pressures and tissue HP contents, along with increases in MPO activity, MDA and NO3(-) /NO2(-) levels, and also plasma levels of TNF-alpha, IL-6, and D-dimer (P < 0.05). However, APC treatment led to significant increases in anastomotic bursting pressures and tissue HP ontents, along with decreases in MPO activity, MDA and NO3(-) /NO2(-) levels, and also plasma levels of TNF-alpha, IL-6, and D-dimer (P < 0.05). This study clearly showed that APC treatment prevented the delaying effects of intra-abdominal sepsis on colonic anastomotic wound healing process. Further clinical studies are required to determine whether APC has a useful role in the enhancement of anastomotic healing during particular surgeries in which sepsis-induced injury occurs.