Nonselective matrix metalloproteinase but not tumor necrosis factor-α inhibition effectively preserves the early critical colon anastomotic integrity

Magnus S Agren, Thomas Levin Andersen, Line Andersen, Christine Bruun Schiødt, Vikas Surve, Troels T Andreassen, Juha Risteli, Lennart E Franzén, Jean-Marie Delaissé, Anne-Marie Heegaard, Lars N Jorgensen

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BACKGROUND: Increased matrix metalloproteinase (MMP) activity has been implicated in the pathogenesis of colorectal anastomotic leakage. Tumor necrosis factor-α (TNF-α) induces MMPs and may influence anastomosis repair. METHODS: We assessed the efficacies of the nonselective hydroxamate MMP inhibitor GM6001, the selective hydroxamate MMP inhibitor AG3340 and a TNF-α antagonist with respect to anastomotic breaking strength of left-sided colon anastomoses in male Sprague-Dawley rats. RESULTS: Systemic GM6001 treatment effectively blocked MMP activity and maintained the initial breaking strength day 0 of the anastomoses when administered subcutaneously as daily depositions (100 mg/kg) or continuously (10 mg/kg/day). In contrast, the anastomotic biomechanic strength was lowered by 55% (p 
TidsskriftInternational Journal of Colorectal Disease
Udgave nummer3
Sider (fra-til)329-337
StatusUdgivet - 2011