Hydroxyethyl starch 130/0.4 augments healing of colonic anastomosis in a rat model of peritonitis

Abstract 

Background

This study was designed to investigate the role of hydroxyethyl starch (HES) 130/0.4 on the wound healing process in left colonic anastomoses in the presence of intra-abdominal sepsis.

Methods

The left colonic anastomosis was performed in 40 rats that were divided into 4 groups: (1) group SHAM, laparatomy plus cecal mobilization (n = 10); (2) group SHAM + HES, HES130/.4–treated controls (n = 10); and (3) group CLP, cecal ligation and puncture (n = 10); (4) group CLP + HES, CLP plus HES130/.4 (n = 10). HES130/.4 was administrated before the construction of colonic anastomosis, 15 mL/kg/24 hours and daily for 4 postoperative days. Anastomotic bursting pressures (ABPs) were measured in vivo on day 5. Tissue samples were obtained for analyses of hydroxyproline (HP) contents, myeloperoxidase (MPO) activity, malondialdehyde (MDA), reduced glutathione (GSH) levels, and nuclear factor-κB (NF-κB) activation. The plasma levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, d-dimer, and protein C (PC) were also measured. Anastomotic granulation tissues were fixed for transmission electron microscopic (TEM) analyses.

Results

Intra-abdominal sepsis led to significant decreases in colonic anastomotic bursting pressures, perianastomotic tissue HP contents, GSH levels, and plasma levels of PC, along with increases in perianastomotic tissue MPO activity, MDA levels, NF-κB activation, and plasma levels of TNF-α, IL-6, and d-dimer. However, HES130/.4 treatment significantly inhibited all these responses. TEM analyses revealed that there was a trend toward a higher density of fibroblast distribution and a higher rate of fibroblast activation in the SHAM- and HES 130/0.4-treated animals, compared with the CLP group.

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. This beneficial effect of HES 130/0.4 can be mainly attributed to its anti-inflammatory and antioxidant properties and beneficial effects of modulating endothelial-associated coagulopathy.

Keywords: HES130.4, Sepsis, Colonic anastomosis, Wound healing, NF-κB, Coagulopathy