Locally applied molgramostim improves wound healing at colonic anastomoses in rats after ligation of the common bile duct

Abstract

Background: Several systemic factors, including jaundice, long-term corticosteroid therapy, diabetes and malnutrition, increase the risk of anastomotic dehiscence. The local application of molgramostim (recombinant human granulocyte-macrophage colony stimulating factor) has been reported to improve impaired dermal wound healing. Since jaundice, one of the systemic risk factors for anastomotic dehiscence, causes significant impairment of anastomotic healing, we hypothesized that locally injected molgramostim could improve the healing of bowel anastomoses in bile-duct-ligated rats used as an experimental model for jaundice.

Methods: Eighty-six Sprague-Dawley rats were randomized into 4 groups of 20-22 animals each as follows: group 1--colonic anastomosis only; group 2--laparotomy followed 7 days later by colonic anastomosis; group 3--common-bile-duct ligation (CBDL) followed 7 days later by colonic anastomosis (control group); group 4--CBDL followed by colonic anastomosis with locally applied molgramostim. Laparotomy was performed under anesthesia in group 2 rats. In groups 3 and 4, laparotomy was followed by ligation and dissection of the common bile duct. After 7 days, colonic anastomosis was performed; in group 4 rats, molgramostim (50 microg) was injected into the perianastomotic area. On postoperative day 3, rats were killed, and the bursting pressures and hydroxyproline levels measured. Two rats from each group were selected for histopathological examination.

Results: The mean bursting pressure in group 4 was significantly higher than that in group 3 (37.8 v. 30.5 mm Hg [p < 0.01]). The mean hydroxyproline level in group 3 was significantly lower than that of the other groups (2.7 v. 3.1-3.5 mg/g tissue [p < 0.01]). On histopathological examination, specimens from group 4 rats showed an increased mononuclear cell population and a smaller gap on the anastomotic line than those from group 3.

Conclusion: The local injection of molgramostim improves healing of the impaired wound in rats subjected to CBDL.

FIG. 3. Cross-section obtained on postoperative day 3 of the anastomosis from a rat in group 4 (common-bile-duct ligation [CBDL] followed by colonic anastomosis and injection of 50 μg molgramostim) indicated that the gap at the anastomotic line is smaller than that in the group with CBDL only. The mononuclear cell population is also increased (hematoxylin–eosin stain; original magnification х20).

FIG. 2. Cross-section of the anastomosis in a rat from group 3 (colonic anastomosis after common-bile-duct ligation) demonstrates impaired anastomotic wound healing with a significant gap in the submucosal layer. There is an abscess formation in the anastomotic area. Mononuclear cell infiltration is decreased (hematoxylin–eosin stain; original magnification х20).

FIG. 1. Cross-section of a specimen from a rat in group 1 (colonic anastomosis only) demonstrates normal anastomotic wound healing on postoperative day 3. The gap between the anastomotic edges is filled by granulation tissue (hematoxylin–eosin stain; original magnification х10).