Oral glutamine and the healing of colonic anastomoses in rats

Abstract

BACKGROUND: Recent evidence has suggested that glutamine is one of the primary energy sources of the colon. The aim of this study was to evaluate the effects of oral glutamine supplementation on the healing of colonic anastomoses in rats. METHODS: Forty-eight adult male Wistar rats, weighing 174.41 +/- 37.39 g, were housed in individual cages. All rats had free access to water and standard rat chow. The rats were randomized to receive daily, for 7 days before the operation and during the postoperative period, 10% L-glutamine (GLN group) or 10% glycine (GLY group) in isonitrogenous and isovolumetric solutions (1.5 g/kg per day), through an orogastric tube. On the eighth day, rats were anesthetized and subjected to 2 colonic transections, one 6 cm distal from the ileocecal valve and another 5 cm distal from the first transection. Bowel continuity was restored by 2 end-to-end, single layer, everted, anastomoses with 8 interrupted sutures (6-0 nylon). After the operation, the rats were kept in individual cages and had free access to water and rat chow. One-half of the rats in each group were killed either on postoperative day 3 or 8, and the 2 colonic anastomoses of each animal were resected and stored in 0.9% saline and 10% formalin for tensile strength and histologic (hematoxylineosin and collagen densitometry) studies, respectively. Student's t-test and Kruskal Wallis tests were used for statistical analysis. RESULTS: Total rupture strength was significantly higher in the GLN group (GLN: 0.068 +/- 0.045 kgf versus GLY: 0.042 +/- 0.027 kgf, p = .04). The mean monocytes infiltrate was significantly smaller in the GLN group (p = .04). The collagen densitometry analysis demonstrated greater percent area of type I (mature) in the GLN group compared with GLY (58.65 +/- 11.70% versus 41.79 +/- 10.54%, p = .0000), respectively. Subgroup analyses according to the day of rat death were still significant: GLN 3: 54.22 +/- 10.02% versus GLY 3: 41.92 +/- 13.31% (p = .04) and GLN 8: 62.63 +/- 12.13% versus GLY 8: 41.67 +/- 7.69% (p = .0004). Type III collagen (immature) percent area was significantly smaller in the GLN group's colonic anastomoses (GLN: p = .0000; GLN 3: p = .04 and GLN 8: p = .0003, respectively). CONCLUSIONS: Perioperative oral glutamine supplementation increases total rupture strength and improves the percent area of mature collagen at the anastomoses sites on postoperative days 3 and 8.

Glutamine is a preferred oxidative fuel of all rapidly dividing cells, including those involved in anastomotic healing, eg, colonocytes and fibroblasts. Additionally, one of the end products of glutamine metabolism is proline, which is essential for the production of collagen. The amount and quality of this collagen can determine the anastomotic strength.