Influence of Hydroxyethyl Starch on Healing of Colonic Anastomosis in a Rat Model of Peritonitis

Abstract

Background: This study was designed to evaluate the role of different intravascular volume replacement regimens of HES 130/0.4 on wound healing process in left colonic anastomoses in the presence of intra-abdominal sepsis induced by murine model of cecal ligation and puncture (CLP). Methods: The left colonic anastomosis was performed in 40 rats that were divided into five groups (n = 8/group): saline controls (30 ml/kg); CLP plus saline (30 ml/kg); CLP plus HES (7.5, 15, or 30 ml/kg, respectively). Saline or HES was treated before the construction of left colonic anastomosis and on a regular daily basis. Anastomotic bursting pressures were measured in vivo on day 5. Tissue samples were obtained for analyses of hydroxyproline (HP) contents, myeloperoxidase (MPO) acivity, malondialdehyde (MDA), reduced glutathione (GSH) levels, and nuclear factor-κ B (NF-κ B) activation. The plasma levels of tumor necrosis factor (TNF)-α and interleukin (IL)-6 were also measured. Results: Intra-abdominal sepsis led to significant decreases in colonic anastomotic bursting pressures, and perianastomotic tissue HP contents and GSH levels, along with increases in perianastomotic tissue MPO activity, MDA levels and NF-κ B activation and plasma levels of TNF-α and IL-6. After treated with HES, these provoked perianastomotic tissue MPO activity, MDA levels, NF-κ B activation, and plasma levels of TNF-α and IL-6 were suppressed and GSH levels were restored, especially in 15 ml/kg HES group. Without obvious influence on systemic nutritional condition, HES 15 ml/kg but not HES 7.5 ml/kg significantly increased anastomotic bursting pressures, and perianastomotic tissue HP contents. However, HES 30 ml/kg even led to adverse effects on anastomotic bursting pressures. Conclusions: This study showed that moderate doses (15 ml/kg) of HES 130/0.4 administration significantly prevented this intraperitoneal sepsis-induced impaired anastomotic healing of the left colon. It also suggested the possibility of poorer anastomotic healing receiving HES at higher doses (30 ml/kg). Clearly, HES 130/0.4 now should not be recommended to use at a high doses postoperatively in sepsis.

Keywords:

• HES130/0.4
• sepsis
• colonic anastomosis
• wound healing
• NF-κB