2005 Abstracts: Effect of Ischemia on Intestinal Anastamotic Healing: The Role of Hypoxia Induced Angiogenesis
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Effect of Ischemia on Intestinal Anastamotic Healing: The Role of Hypoxia Induced Angiogenesis
Shahzeer Karmali, Laurie Wallace, Manoj Raval, Gary Martin, Anthony Maclean, Donald Buie, David Sigalet, University of Calgary, Calgary, Alberta, Canada
ABSTRACT:
Background: Impaired healing and subsequent leakage of intestinal anastamosis is a major complication of intestinal surgery. Studies have shown that adequate local tissue oxygen level is a significant determinant of anastamotic integrity. Prior studies by our lab have demonstrated that systemic hypoxia impairs intestinal wound healing; with a reduction in anastamotic burst pressure. (Raval et al. Proc. DCR 2003 Jun) Objective: To determine if hypoxic induced impairment in wound healing is due to a reduction in angiogenic cytokine production and/or subsequent neo-vascularization. Methods: Seventeen juvenile male Sprague-Dawley rats underwent colonic transection with immediate re-anastamosis and were placed in a normoxic (FiO2 21%) or hypoxic (FiO2 11%) environments for seven days. Local tissue hypoxia was confirmed by direct measurement. At sacrifice peri-anastamotic tissue samples were examined for neo-vascularization with Von Willebrand factor (VWF) immunohistochemical staining and Vascular Endothelial Growth Factor (VEGF) Western blot analysis Results: Hypoxia resulted in a qualitative and quantitative increase in neo-vascularization in hypoxic versus normoxic conditions (overall mean VWF neo-vessel density 47.12 +/- 10.60 vs. 23.29 +/- 10.17 p=0.0005). In parallel, mean VEG F protein expression was elevated in hypoxic versus normoxic specimens (247.1 +/- 9.5 OD/mm2 vs. 142 +/- 10.6 OD/mm2; p<0.002) Conclusion: We have previously shown that systemic hypoxia translates into local tissue hypoxia in surgical anastamotic specimens with a reduced mean burst pressure. The result of the present study demonstrates that both cytokine-mediated angiogenic stimulation (VEG F) and directly visualized VWF neo-vascularization is increased in hypoxic tissues. These findings suggest that the deleterious effects of hypoxia on wound healing occur downstream of re-vascularization, affecting processes such as collagen synthesis or cross-linking. Key Words: Anastamosis, Surgical Colon Hypoxia Wound Healing Angiogenesis Von Willebrands Factor (VWF) Vascular Endothelial Growth Factor (VEG F)
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