Effect of matrix metalloproteinase inhibition on colonic anastomotic healing in rats.
Wound strength depends on the balance between collagen synthesis and degradation; however, the role of collagen breakdown in wound healing is still not well understood. We investigated the role of matrix metalloproteinases in wound healing by using BE16627B, a matrix metalloproteinase inhibitor. Identical surgical procedures consisting of a colonic anastomosis (single-layer, inverted) and implantation of an osmotic pump in the back were performed in male Sprague-Dawley rats weighing 270 to 290 grams. The animals were randomly assigned to receive either BE16627B (n = 10) dissolved in dimethylsulfoxide and diluted with ethylene glycol at a dosage of 2.4 mg/rat/day for 3 days or the vehicle solution alone (n = 11). The solutions were administered through the surgically implanted osmotic pumps. The animals were killed 4 days after surgery, and the colonic bursting pressure (mm Hg) and hydroxyproline concentration (microg/mg wet tissue, index of collagen) were measured. The administration of BE16627B enhanced colonic anastomotic healing, as measured by the increase in the colonic bursting pressure (160 +/- 12 vs. 125 +/- 7 mm Hg; P < 0.05) and the increase in the soluble fraction of collagen (0.27 +/- 0.01 vs. 0.21 +/- 0.01 microg/mg wet tissue; P < 0.01) in the anastomosis. Histologic examination of the tissue revealed that the use of BE16627B resulted in the preservation of the multilayered colonic structure and increased the network of collagen between both ends of the colon in the thickening submucosal layer. These findings demonstrate that the inhibition of matrix metalloproteinase activity influences colonic anastomotic healing, indicating a potential mechanism for enhancing anastomotic healing.
Kiyama
T
T
Department of Surgery I, Nippon Medical School, Tokyo, Japan. kiyama@nms.ac.jp
Onda
M
M
Tokunaga
A
A
Efron
D T
DT
Barbul
A
A
D000714:Anastomosis, Surgical / Q000009:adverse effects; D000818:Animals; D001835:Body Weight; D003106:Colon / Q000473:pathology / Q000601:surgery*; D004151:Dipeptides / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D007413:Intestinal Mucosa / Q000473:pathology / Q000601:surgery*; D008297:Male; D061965:Matrix Metalloproteinase Inhibitors; D020782:Matrix Metalloproteinases / Q000502:physiology; D015596:Nutrition Assessment; D011480:Protease Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013386:Succinates / Q000494:pharmacology / Q000627:therapeutic use*; D014945:Wound Healing / Q000187:drug effects* / Q000502:physiology
D004151:Dipeptides; D061965:Matrix Metalloproteinase Inhibitors; D011480:Protease Inhibitors; D013386:Succinates; C085667:L-N-(N-hydroxy-2-isobutylsuccinamoyl)seryl-L-valine; D020782:Matrix Metalloproteinases