Oral administration of alanyl-glutamine and glutamine improve random pattern dorsal skin flap survival in rats

Skin flap necrosis is the most common postoperative side effect in reconstructive
surgeries. Glutamine (GLN) has been shown to accelerate wound healing process. The purpose of
this study was to evaluate the effects of GLN either in free form or in the dipeptide form along with
L- alanyl (Ala-GLN) on random skin flaps survival in rats.
Materials and Methods: Dorsal skin flaps with caudal bases (8 ×2 cm) were established in 24 adult
male Wistar rats. Then, the animals were randomly assigned into 3 groups (n=8). Control, GLN (0.75
g/kg) and Ala-GLN (0.75 g/kg). All groups administrated orally 24 and 6 hr before flap elevation
and continued repeatedly daily until 7 days postoperation. The flap survival rate and vascular
density using histological analysis were evaluated. Vascular endothelial growth factor (VEGF) by
immunohistochemical method was determined.
Results: Seven days after surgery, the mean surviving area in the GLN and Ala-GLN groups were
significantly greater than in the untreated control group (P<0.001). Furthermore, in comparison with
the control group, the number of blood vessels and VEGF-positive cells in treated groups with GLN and
Ala-GLN were significantly higher. However, no significant differences were observed between treated
groups with GLN and Ala-GLN.
Conclusion: The findings from this study indicate that oral administration of GLN in free form or in the
dipeptide (Ala-GLN) could promote neovascularization and improve skin flap survival in rats.