BACKGROUND: Inadequate healing and consequent leakage from bowel anast
omoses are a significant cause of postoperative morbidity and mortalit
y. Systemic application of keratinocyte growth factor (KGF) has been s
hown to promote mucosal healing in models of colitis in rats and mice.
The aim of the present study was to evaluate the effect of systemic K
GF administration on healing of colonic anastomoses in rats. METHODS:
Rats underwent laparotomy, division of the left colon, and sigmoido-si
gmoidosto my. KGF (5 mg/kg) or vehicle were administered intraperitone
ally in two groups (n = 30 per group) 12 hours prior to surgery, and t
hen once daily until sacrifice (6 animals per group; 2, 4, 7, 12, and
21 days after surgery). Bursting pressure measurements, histologic eva
luation, morphometric analysis, mucin and collagen staining, and hydro
xyproline measurements of the anastomotic site were performed. RESULTS
: Administration of KGF significantly increased anastomotic bursting p
ressure on postoperative days 2, 4, and 7 by 34%, 49%, and 19%, respec
tively. Histology, mucin staining, and measurements of the colonic cry
pt depth showed markedly less extended inflammation with an increased
acidic mucin content and a significantly thickened mucosal layer in th
e KGF treated group when compared with vehicle-treated animals. CONCLU
SIONS: KGF promotes healing of colonic anastomoses in rats during a 1-
week postoperative period following large bowel surgery. KGF may be ac
ting to accelerate host reparative processes as well as to enhance pro
tection of the anastomotic wound bed by increased colonic epithelium p
roliferation, increased mucus production, and reduction of the inflamm
atory activity at the anastomotic site. (C) 1998 by Excerpta Medica, I
nc.