Can Human Recombinant Epidermal Growth Factor Improve Ischemia and Induce Healing of Anastomosis in an Experimental Study in a Rabbit Model?
OBJECTIVE
Anastomotic leaks following intestinal operations may cause devastating effects on patients. Ischemia may also occur at the intestinal walls in the presence of strangulations. In this study, we examined the effects of human recombinant (Hr)-epidermal growth factor (EGF) given at a single intramural dose into the intestinal walls and daily intraperitoneal cavity on ischemia and the healing process of anastomosis.


METHODS
Sixteen male New Zeland white rabbits were randomly divided into four groups (n = 4 in each group). In Group 1, two different segments of ileum were identified and, then, transected and the free ends were sutured each other. In the other groups, ischemia was induced by ligating the mesenteric vascular arcade. After the ischemic induction, Group 2 received intramural injections of %0.9 saline, Group 3 received intramural injections of a single dose of EGF, and Group 4 received intramural and intraperitoneal injections of EGF. Bursting pressures and tissue hydroxyproline levels were analyzed. Necrosis, fibroblastic activity, collagen deposition and neovascularization were also studied.


RESULTS
The mean levels of bursting pressures in Group 4 (148.6 ± 25.3 mmHg) were higher than Group 2 (70 ± 21.5 mmHg) (p = 0.001). The mean level of bursting pressures was not statistically significant between Group 1 (170.1 ± 35 mmHg) and Group 4 (p = 0.073). Hydroxyproline levels in Group 2 were lower than Groups 3 and 4. There was a statistically significant difference in the mucosal ischemia, mucosal healing and degree of adhesion, but not in the mural anastomotic healing among the groups.


CONCLUSIONS
Intramural injection with daily intraperitoneal administration of low-dose EGF enhances the bursting pressure and collagen accumulation in ischemic anastomosis, improving many histological variables associated with ischemic intestinal anastomosis.
a Department of General Surgery , Gulhane Military Medical Faculty.
Rahman
R
Şenocak
a Department of General Surgery , Gulhane Military Medical Faculty.
Mustafa Tahir
MT
Özer
a Department of General Surgery , Gulhane Military Medical Faculty.
Şahin
Ş
Kaymak
a Department of General Surgery , Gulhane Military Medical Faculty.
Zafer
Z
Kılbaş
b Department of Pathology.
Armağan
A
Günal
c Department of Biochemistry , Ankara , Turkey.
Metin
M
Uyanık
a Department of General Surgery , Gulhane Military Medical Faculty.
Orhan
O
Kozak
D000714:Anastomosis, Surgical / Q000009:adverse effects; D057868:Anastomotic Leak / Q000188:drug therapy*; D000818:Animals; D003094:Collagen / Q000378:metabolism; D066255:EGF Family of Proteins / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D006909:Hydroxyproline / Q000378:metabolism; D007082:Ileum / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D007274:Injections, Intraperitoneal; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology / Q000601:surgery*; D007511:Ischemia / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D011817:Rabbits; D011897:Random Allocation; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D014945:Wound Healing / Q000187:drug effects*
D066255:EGF Family of Proteins; D011994:Recombinant Proteins; D003094:Collagen; D006909:Hydroxyproline
Hr-EGF; anastomosis; angiogenesis; collagen synthesis; ischemia; wound healing