Abstract
PURPOSE: Emergency resections for colonic obstruction are accompanied with increased risk of anastomotic dehiscence. Elevated local degradation of submucosal collagens by matrix metalloproteinases may predispose to anastomotic leakage. This study was designed to study the effect of colon obstruction and surgical trauma on matrix metalloproteinase activities and correlate these results to collagen concentration in the colon wall. METHODS: Colonic obstruction was induced in male, Sprague-Dawley rats (n = 58) by applying a constricting silicone ring around the left colon 3 cm above the peritoneal reflection. After four days of obstruction, 2-mm wide colonic segments were resected approximately 3 mm proximal and 3 mm distal to the stenosis for biochemical analyses. Colonic segments at corresponding locations were obtained from sham-operated rats (n = 5) without obstruction but with silicone ring placed adjacent to colon and from normal, nontraumatized rats (n = 10). Matrix metalloproteinase activity was determined by liberation of fragmented collagens from homogenized colonic tissue incubated ex vivo. Matrix metalloproteinase-2 specifically was analyzed by gelatin zymography. RESULTS: Endogenous collagenolysis by matrix metalloproteinases increased (P < 0.001) in colon as a consequence of obstruction (4.1-fold) and trauma (1.7-fold) compared with normal colon. In the proximity of the colon stenosis, total matrix metalloproteinase activity and matrix metalloproteinase-2 were significantly (P < 0.05) higher above than below the obstruction. Total activity was 22.9 (13.1–32.9) units/mg collagen proximal and 16.6 (12.7–18.4) units/mg collagen distal to the stenosis. Collagen concentration correlated inversely (r = −0.76; P < 0.001) with total matrix metalloproteinase activity. CONCLUSION: Colonic obstruction and trauma up-regulated matrix metalloproteinases and decreased collagen concentration in colonic wall.
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References
HS Chen SM Sheen-Chen (2000) ArticleTitleObstruction and perforation in colorectal adenocarcinoma Surgery 127 370–376
RP Waldron IA Donovan (1986) ArticleTitleMortality in patients with obstructing colorectal cancer Ann R Coll Surg Engl 68 219–221
NS Runkel U Hinz T Lehnert HJ Buhr C Herfarth (1998) ArticleTitleImproved outcome after emergency surgery for cancer of the large intestine Br J Surg 85 1260–1265
KJ Buechter C Boustany R Caillouette I Cohn SuffixJr (1988) ArticleTitleSurgical management of the acutely obstructed colon. A review of 127 cases Am J Surg 156 163–168
R Golub RW Golub R Cantu SuffixJr HD Stein (1997) ArticleTitleA multivariate analysis of factors contributing to leakage of intestinal anastomoses J Am Coll Surg 184 364–372
UP Khot AW Lang K Murali MC Parker (2002) ArticleTitleSystematic review of the efficacy and safety of colorectal stents Br J Surg 89 1096–1102
H Christensen H Oxlund (1994) ArticleTitleGrowth hormone increases the collagen deposition rate and breaking strength of left colonic anastomoses in rats Surgery 116 550–556
H Christensen J Chemnitz BC Christensen H Oxlund (1995) ArticleTitleCollagen structural organization of healing colonic anastomoses and the effect of growth hormone treatment Dis Colon Rectum 38 1200–1205
MY Rabau A Hirshberg Y Hiss D Dayan (1995) ArticleTitleIntestinal anastomosis healing in rat Exp Mol Pathol 62 160–165
T Hendriks WL Hesp AA Klompmakers EJ Lubbers HH de Boer (1985) ArticleTitleSolubility of tissue hydroxyproline in experimental intestinal anastomoses Exp Mol Pathol 43 253–259
M Stumpf W Cao U Klinge B Klosterhalfen R Kasperk V Schumpelick (2002) ArticleTitleCollagen distribution and expression of matrix metalloproteinases 1 and 13 in patients with anastomotic leakage after large-bowel surgery Langenbecks Arch Surg 386 502–506
A Törnqvist P Blomquist J Ahonen H Jiborn B Zederfeldt (1988) ArticleTitleThe effect of stenosis on collagen metabolism in the colonic wall. Studies in the rat Acta Chir Scand 154 389–393
H Nagase JF Woessner SuffixJr (1999) ArticleTitleMatrix metalloproteinases J Biol Chem 274 21491–4
FJ Savage DL Lacombe RM Hembry PB Boulos (1998) ArticleTitleEffect of colonic obstruction on the distribution of matrix metalloproteinases during anastomotic healing Br J Surg 85 72–75
I Syk MS Ågren D Adawi B Jeppsson (2001) ArticleTitleInhibition of matrix metalloproteinases enhances breaking strength of colonic anastomoses in an experimental model Br J Surg 88 228–234
JF Woessner SuffixJr (1995) ArticleTitleQuantification of matrix metalloproteinases in tissue samples Methods Enzymol 248 510–528
JF Woessner SuffixJr (1977) ArticleTitleA latent form of collagenase in the involuting rat uterus and its activation by a serine proteinase Biochem J 161 535–542
DD Dean OE Muniz I Berman et al. (1985) ArticleTitleLocalization of collagenase in the growth plate of rachitic rats J Clin Invest 76 716–722
H Nakagawa M Isaji M Hayashi S Tsurufuji (1981) ArticleTitleSelective inhibition of collagen breakdown by proteinase inhibitors in granulation tissue in rats J Biochem (Tokyo) 89 1081–1090
MS Ågren (1993) ArticleTitleZinc oxide increases degradation of collagen in necrotic wound tissue Br J Dermatol 129 221–223
K Yoshihara O Matsushita J Minami A Okabe (1994) ArticleTitleCloning and nucleotide sequence analysis of the colH gene from Clostridium histolyticum encoding a collagenase and a gelatinase J Bacteriol 176 6489–6496
HP Marti L McNeil M Davies J Martin DH Lovett (1993) ArticleTitleHomology cloning of rat 72 kDa type IV collagenase Biochem J 291 441–446
JW van der Stappen T Hendriks HH de Boer BM de Man JJ de Pont (1992) ArticleTitleCollagenolytic activity in experimental intestinal anastomoses. Differences between small and large bowel and evidence for the presence of collagenase Int J Colorectal Dis 7 95–101
MJ Koruda RH Rolandelli (1990) ArticleTitleExperimental studies on the healing of colonic anastomoses J Surg Res 48 504–515
A Törnqvist P Blomquist H Jiborn B Zederfeldt (1990) ArticleTitleAnastomotic healing after resection of left-colon stenosis: effect on collagen metabolism and anastomotic strength. An experimental study in the rat Dis Colon Rectum 33 217–221
EH Kerkvliet AJ Docherty W Beertsen V Everts (1999) ArticleTitleCollagen breakdown in soft connective tissue explants is associated with the level of active gelatinase A (MMP-2) but not with collagenase Matrix Biol 18 373–380
RT Aimes JP Quigley (1995) ArticleTitleMatrix metalloproteinase-2 is an interstitial collagenase. Inhibitor-free enzyme catalyzes the cleavage of collagen fibrils and soluble native type I collagen generating the specific 3/4- and 1/4-length fragments J Biol Chem 270 5872–5876
MH Verhofstad RM Lomme BM de Man T Hendriks (2002) ArticleTitleIntestinal anastomoses from diabetic rats contain supranormal levels of gelatinase activity Dis Colon Rectum 45 554–561
X Fu SY Kassim WC Parks JW Heinecke (2001) ArticleTitleHypochlorous acid oxygenates the cysteine switch domain of pro-matrilysin (MMP-7). A mechanism for matrix metalloproteinase activation and atherosclerotic plaque rupture by myeloperoxidase J Biol Chem 276 41279–87
A Törnqvist A Forsgren K Faldt H Jiborn B Zederfeldt (1991) ArticleTitleBacterial load and inflammatory reaction in the bowel wall after colonic obstruction. An experimental study in rats Eur J Surg 157 539–542
VC Mudera R Pleass M Eastwood et al. (2000) ArticleTitleMolecular responses of human dermal fibroblasts to dual cues Cell Motil Cytoskeleton 45 1–9
IH De Hingh MA Siemonsma BM De Man RM Lomme T Hendriks (2002) ArticleTitleThe matrix metalloproteinase inhibitor BB-94 improves the strength of intestinal anastomoses in the rat Int J Colorectal Dis 17 348–354
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Syk, I., Mirastschijski, U., Jeppsson, B.W. et al. Experimental Colonic Obstruction Increases Collagen Degradation by Matrix Metalloproteinases in the Bowel Wall. Dis Colon Rectum 46, 1251–1259 (2003). https://doi.org/10.1007/s10350-004-6723-x
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DOI: https://doi.org/10.1007/s10350-004-6723-x