Adrenomedulline improves ischemic left colonic anastomotic healing in an experimental rodent model.
BACKGROUND
Leakage from colonic anastomosis is a major complication causing increased mortality and morbidity. Ischemia is a well-known cause of this event. This study was designed to investigate the effects of adrenomedullin on the healing of ischemic colon anastomosis in a rat model.


METHODS
Standardized left colon resection 3 cm above the peritoneal reflection and colonic anastomosis were performed in 40 Wistar rats that were divided into four groups. To mimic ischemia, the mesocolon was ligated 2 cm from either side of the anastomosis in all of the groups. The control groups (1 and 2) received no further treatment. The experimental groups (3 and 4) received adrenomedullin treatment. Adrenomedullin therapy was started in the perioperative period in group 3 and 4 rats (the therapeutic groups). Group 1 and group 3 rats were sacrificed on postoperative day 3. Group 2 and group 4 rats were sacrificed on postoperative day 7. After careful relaparotomy, bursting pressure, hydroxyproline, malondialdehyde, interleukin 6, nitric oxide, vascular endothelial growth factor, and tumor necrosis factor alpha levels were measured. Histopathological characteristics of the anastomosis were analyzed.


RESULTS
The group 3 animals had a significantly higher bursting pressure than group 1 (p<0.05). Hydroxyproline levels in group 1 were significantly lower than in group 3 (p<0.05). The mean bursting pressure was significantly different between group 2 and group 4 (p<0.05). Hydroxyproline levels in groups 3 and 4 were significantly increased by adrenomedullin therapy relative to the control groups (p<0.05). When all groups were compared, malondialdehyde and nitric oxide were significantly lower in the control groups (p<0.05). When vascular endothelial growth factor levels were compared, no statistically significant difference between groups was observed. Interleukin 6 and tumor necrosis factor alpha were significantly decreased by adrenomedullin therapy (p<0.05). The healing parameters and inflammatory changes (e.g., granulocytic cell infiltration, necrosis, and exudate) were significantly different among all groups (p<0.05).


CONCLUSIONS
Adrenomedullin had positive effects on histopathologic anastomotic healing in this experimental model of ischemic colon anastomosis.
Department of Surgery, Okmeydani Education and Research Hospital, Okmeydani, Istanbul, Turkey. drkaratepe@yahoo.com
Oguzhan
O
Karatepe
Idris
I
Kurtulus
Orhan
O
Yalcin
Muharrem
M
Battal
Gulcin
G
Kamali
Timucin
T
Aydin
D053607:Adrenomedullin / Q000627:therapeutic use*; D000714:Anastomosis, Surgical; D057868:Anastomotic Leak / Q000188:drug therapy; D000818:Animals; D003106:Colon / Q000098:blood supply* / Q000601:surgery*; D004195:Disease Models, Animal; D005260:Female; D007511:Ischemia / Q000188:drug therapy* / Q000473:pathology; D011183:Postoperative Complications / Q000517:prevention & control; D011184:Postoperative Period; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D014665:Vasodilator Agents / Q000627:therapeutic use*; D014945:Wound Healing / Q000187:drug effects* / Q000502:physiology
D014665:Vasodilator Agents; D053607:Adrenomedullin