Local VEGF administration enhances healing of colonic anastomoses in a rabbit model.
OBJECTIVE
Many studies report the role of vascular endothelial growth factor (VEGF) in wound healing, but few describe local VEGF administration to the digestive tract. Leakage from colonic anastomoses, including those due to ischemia, represents a major complication causing increased mortality and morbidity. Angiogenesis is crucial to anastomotic healing and restoration of blood supply, and VEGF is a potent angiogenic factor showing improved healing in various models of reconstruction and anastomosis. Here, we examine the effects of local VEGF-A(165) administration on postoperative rabbit colon anastomosis.


METHODS
Two colotomies per animal were made in the sinistral colon on opposite sides of the mesentery. Randomly assigned VEGF (10 microg/0.1 ml) or saline (0.1 ml) was injected into the muscularis propria on both sides of each colonic anastomosis before closing the access laparotomy using single-layer sutures. On postoperative days 3, 4 and 7, the bursting pressure of partially healed anastomoses was measured. On postoperative day 4, anastomotic tissues were examined for the following: hydroxyproline; histopathologically for inflammatory infiltrate and tissue organization and immunohistochemically for capillary proliferation and density; vessel density of midzone collaterals around anastomoses by microangiography.


RESULTS
Compared to saline, VEGF administration significantly improved bursting pressure (p = 0.014, paired t test) and increased hydroxyproline (p = 0.027, paired t test) on postoperative day 4. Inflammatory cell infiltration and fibroblast proliferation were prominent, and submucosal capillary vascular counts were significantly higher for VEGF.


CONCLUSIONS
Administration of VEGF to colonic anastomosis accelerates wound healing and strengthens the anastomosis by increased angiogenesis.
Department of Surgery, Tokai University School of Medicine, Isehara, Japan. masa0225@d7.dion.ne.jp
M
M
Ishii
E
E
Tanaka
T
T
Imaizumi
Y
Y
Sugio
T
T
Sekka
M
M
Tanaka
M
M
Yasuda
N
N
Fukuyama
Y
Y
Shinozaki
K
K
Hyodo
K
K
Tanioka
R
R
Mochizuki
T
T
Kawai
H
H
Mori
H
H
Makuuchi
D000714:Anastomosis, Surgical; D000792:Angiography; D000818:Animals; D003106:Colon / Q000098:blood supply / Q000378:metabolism / Q000473:pathology / Q000601:surgery*; D006909:Hydroxyproline / Q000378:metabolism; D008297:Male; D018919:Neovascularization, Physiologic / Q000187:drug effects; D011312:Pressure; D011817:Rabbits; D042461:Vascular Endothelial Growth Factor A / Q000008:administration & dosage*; D014945:Wound Healing / Q000187:drug effects*
D042461:Vascular Endothelial Growth Factor A; D006909:Hydroxyproline