Stasis predisposes ileal pouch inflammation in a rat model of ileal pouch-anal anastomosis.
BACKGROUND
While restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) has become the definitive surgical treatment for patients suffering from chronic ulcerative colitis (CUC), pouchitis still remains a major late complication. Fecal stasis has been implicated in the etiology of ileal inflammation; however, the mechanism(s) remain unclear, in part due to the lack of an animal model. Our goal was to surgically mimic the IPAA procedure in a rat to investigate the hypothesis that stasis leads to biochemical changes that predispose the ileal pouch to inflammation.


METHODS
Thirty-two Sprague-Dawley rats underwent total colectomy with either straight ileorectal (IRA) or IPAA, and 11 nonoperated rats served as controls (Controls). Twenty-one d postoperatively, 48 h serial barium radiographs and 12 h charcoal transit follow-through studies were performed. Following sacrifice, ileal tissue was harvested for the measurement of myeloperoxidase activity (MPO) activity, intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) mRNA levels, and histology.


RESULTS
Serial barium radiographs showed stasis in the ileal pouch compared with IRA animals, and charcoal transit times that were two times longer (P ≤ 0.05) than that in the straight IRA rats. Ileal pouch MPO levels were significantly elevated in the IPAA rats compared with the straight IRA rats. ICAM-1 and VCAM-1 mRNA levels were not associated with neutrophil infiltration.


CONCLUSIONS
These studies showed that ileal pouch stasis predisposes biochemical and histological evidence of ileal pouch mucosal inflammation. Studies such as this may provide the rationale for novel, adjunct therapies for the management of pouchitis in patients having undergone IPAA for CUC.
Stucchi
Arthur F
AF
Department of Surgery, Boston University School of Medicine, Boston, Massachusetts 02118, USA.
Shebani
Khaled O
KO
Reed
Karen L
KL
Gower
Adam C
AC
Alapatt
Michael F
MF
Crivello
Keith M
KM
McClung
James P
JP
Becker
James M
JM
D001003:Anal Canal / Q000601:surgery; D000714:Anastomosis, Surgical; D000818:Animals; D001464:Barium; D003093:Colitis, Ulcerative / Q000601:surgery*; D039021:Colonic Pouches / Q000473:pathology / Q000502:physiology*; D003672:Defecation / Q000502:physiology; D004195:Disease Models, Animal; D005769:Gastrointestinal Motility / Q000502:physiology*; D007082:Ileum / Q000601:surgery; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics; D008297:Male; D008871:Microvilli / Q000473:pathology; D009195:Peroxidase / Q000378:metabolism; D019449:Pouchitis / Q000000981:diagnostic imaging / Q000276:immunology* / Q000503:physiopathology*; D012333:RNA, Messenger / Q000378:metabolism; D011859:Radiography; D051381:Rats; D017207:Rats, Sprague-Dawley
D012333:RNA, Messenger; D018799:Intercellular Adhesion Molecule-1; D001464:Barium; D009195:Peroxidase