title: Intraperitoneally applied gentamicin increases collagen content and mechanical stability of colon anastomosis in rats.
abstract: BACKGROUND
  Anastomotic leakage remains a serious complication in colorectal surgery, and is being caused by a multitude of factors. Recent reports reveal changes of the extracellular matrix as risk factors as well as gentamicin as a potential agent to influence wound healing. This experimental study was initiated to investigate the influence of intraperitoneally applied gentamicin on colonic anastomotic wound healing and in particular on mechanical stability, overall collagen content and collagen type I/III ratio.
  
  
  METHODS
  Sixty Sprague Dawley rats were randomized to one of two groups. In each animal, a standard transverse colonic end-to-end anastomosis was performed. Immediately postoperative, either 5 ml gentamicin (1 ml/kg bodyweight) or NaCl 0.9% was applied intraperitoneally. On postoperative days 3, 5, and 14, ten of the animals in each group were sacrificed. Measurements of the anastomosis bursting pressure were performed on postoperative days 3 and 5. At each explantation time, the collagen per protein ratio, the collagen types I/III ratio, and both the expression of MMP-2, -9, and Ki67 were analyzed.
  
  
  RESULTS
  None of the animals died. None of the rats exhibited clinical evidence of anastomotic leakage. The bursting strength in the gentamicin group was significantly elevated on postoperative day 5. Both the overall collagen content and the collagen type I/III ratio in the gentamicin group were significantly increased 3, 5, and 14 days postoperatively compared to the control group. The expression of MMP-9 was significantly elevated in the gentamicin group both 3 and 5 days postoperatively. In contrast, there were no significant differences in the expression of MMP-9 14 days postoperatively. All investigated samples demonstrated positive staining for MMP-2 and Ki67 without statistically significant differences at any term, respectively.
  
  
  CONCLUSIONS
  The present data confirm that intraperitoneally applied gentamicin is able to enhance healing and stability of colonic anastomosis due to an increase of both the overall collagen content and collagen type I/III ratio.
authors.affiliation: Department of Surgery, Aachen University Hospital, Pauwelsstr. 30, 52074 Aachen, Germany. mbinneboesel@ukaachen.de
authors.forename: Marcel
authors.initials: M
authors.lastname: Binnebösel
authors.forename: Karsten
authors.initials: K
authors.lastname: Junge
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Kaemmer
authors.forename: Carsten J
authors.initials: CJ
authors.lastname: Krones
authors.forename: Svetlana
authors.initials: S
authors.lastname: Titkova
authors.forename: Michael
authors.initials: M
authors.lastname: Anurov
authors.forename: Volker
authors.initials: V
authors.lastname: Schumpelick
authors.forename: Uwe
authors.initials: U
authors.lastname: Klinge
mesh_terms: D000714:Anastomosis, Surgical; D000818:Animals; D003094:Collagen / Q000378:metabolism*; D024042:Collagen Type I / Q000378:metabolism; D024061:Collagen Type III / Q000378:metabolism; D003106:Colon / Q000187:drug effects* / Q000201:enzymology / Q000601:surgery*; D005839:Gentamicins / Q000008:administration & dosage* / Q000494:pharmacology*; D007274:Injections, Intraperitoneal; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D055595:Mechanical Phenomena / Q000187:drug effects*; D011312:Pressure; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D024042:Collagen Type I; D024061:Collagen Type III; D005839:Gentamicins; D019394:Ki-67 Antigen; D003094:Collagen; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9