Positive effects of phenytoin on experimental colonic anastomoses.
OBJECTIVE
Anastomotic dehiscence following colorectal surgery is a significant cause of morbidity and mortality. Phenytoin has wound-healing promoting and collagenase inhibitory effects. This study assessed these effects on healing of experimental colonic anastomoses in a rat model.


METHODS
Ninety Wistar rats weighing 240-290 g were divided into six groups: 3rd-day control group (n=15), 3rd-day oral administration of phenytoin (n=15), 3rd-day rectal administration of phenytoin (n=15), 7th-day control group (n=15), 7th-day oral administration of phenytoin (n=15), and 7th-day rectal administration of phenytoin (n=15). In oral phenytoin groups the agent was given at 10 mg/kg daily per orogastric route by 4-F fine feeding catheter; in rectal phenytoin RAP groups the agent was administered at 10 mg/0.5 cc daily to the anastomoses transrectally via a fine anal catheter.


RESULTS
There were significantly higher anastomosis bursting pressure values and hydroxyproline contents in phenytoin groups than in controls. In histopathological examination it was seen that phenytoin treatment caused greater collagen deposition, fibroblast, and blood vessel ingrowth than in controls. Immunohistochemical analysis showed the stimulatory effect of phenytoin in expression of vascular endothelial growth factor and basic fibroblast growth factor. Anastomosis bursting pressure, histopathological analysis, hydroxyproline content, and immunohistochemical results were better in the groups with rectal administration than in those with oral administration.


CONCLUSIONS
These results had showed us that phenytoin administration resulted in enhanced stability of colonic anastomoses during the first postoperative week and rectal administration showed better results than oral administration.
D000284:Administration, Oral; D000285:Administration, Rectal; D000714:Anastomosis, Surgical; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D003094:Collagen / Q000378:metabolism; D003106:Colon / Q000098:blood supply / Q000378:metabolism / Q000601:surgery*; D004334:Drug Administration Schedule; D005347:Fibroblasts / Q000378:metabolism; D006909:Hydroxyproline / Q000378:metabolism; D007150:Immunohistochemistry; D008365:Manometry; D023421:Models, Animal; D010672:Phenytoin / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013529:Surgical Wound Dehiscence / Q000517:prevention & control; D042461:Vascular Endothelial Growth Factor A; D014945:Wound Healing / Q000187:drug effects*
D000927:Anticonvulsants; D042461:Vascular Endothelial Growth Factor A; D010672:Phenytoin; D003094:Collagen; D006909:Hydroxyproline