Insulin-like growth factor I improves aspects of mycophenolate mofetil-impaired anastomotic healing in an experimental model.
BACKGROUND
Patients taking immunosuppressants after transplantation may require intestinal surgery. Mycophenolate mofetil (MMF) has been found to impair the healing of colonic anastomoses in rats. This study examined whether insulin-like growth factor (IGF) I prevents MMF impairment of anastomotic healing.


METHODS
Sixty-three rats were divided into three groups (MMF, MMF/IGF and control). Animals underwent a sigmoid colon anastomosis with a 6/0 suture, and were killed on days 2, 4 and 6 after surgery. Investigations included bursting pressure measurement, morphometric analysis, and assessment of mucosal proliferation by 5-bromo-2'-deoxyuridine and Ki67 immunohistochemistry of the anastomoses.


RESULTS
The leak rate was three of 21, one of 20 and two of 20 in the MMF, MMF/IGF-I and control groups respectively. Anastomotic bursting pressures were significantly lower in the MMF group than in the control group on days 2 and 4, but there was no significant difference by day 6. Values in the MMF/IGF-I and control groups were similar. Colonic crypt depth was significantly reduced in MMF-treated animals on days 2 and 4, but this impairment was attenuated by IGF-I on day 4. Similarly, IGF-I reduced the negative impact of MMF on mucosal proliferation on days 2 and 6.


CONCLUSIONS
Exogenous IGF-I improves some aspects of MMF-impaired anastomotic healing.
Inglin
R A
RA
Department of Visceral and Transplantation Surgery, Inselspital, University of Berne, CH-3010 Berne, Switzerland.
Baumann
G
G
Wagner
O J
OJ
Candinas
D
D
Egger
B
B
D000714:Anastomosis, Surgical; D000818:Animals; D000963:Antimetabolites; D001973:Bromodeoxyuridine; D049109:Cell Proliferation; D012809:Colon, Sigmoid / Q000166:cytology / Q000502:physiology / Q000601:surgery; D007150:Immunohistochemistry; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D007413:Intestinal Mucosa / Q000166:cytology; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D009173:Mycophenolic Acid / Q000009:adverse effects / Q000031:analogs & derivatives*; D011312:Pressure; D051381:Rats; D017207:Rats, Sprague-Dawley; D013529:Surgical Wound Dehiscence / Q000473:pathology / Q000503:physiopathology; D014945:Wound Healing / Q000187:drug effects* / Q000502:physiology
D000963:Antimetabolites; D007166:Immunosuppressive Agents; D019394:Ki-67 Antigen; D007334:Insulin-Like Growth Factor I; D001973:Bromodeoxyuridine; D009173:Mycophenolic Acid