Abstract 17828: Preconditioning of Mice with a Prolyl Hydroxylase Inhibitor, Dimethyloxalylglycine, Prevents Skin Flap Necrosis
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Background- Local skin flaps often present with flap necrosis caused by critical disturbance of blood supply. Because hypoxia-inducible factor 1 (HIF-1) has a pivotal role in ischemic vascular responses, we assessed the hypothesis that preoperative stabilization of HIFs using prolyl hydroxylases (PHD) inhibitor contributes to improvement of skin flap survival. Methods and Results- Mice with ischemic skin flap on the dorsum were treated with PHD inhibitor dimethyloxalylglycine (DMOG) 48hr prior to operation by intraperitoneal administration. Immunoblot assay revealed sustained up-regulation of HIF-1α protein at pre- and postoperative states in the skin. Survival area of flap and the number of CD31 positive vessels at proximal part of flaps in DMOG-treated mice were significantly increased at day seven (20.6±4.9% vs. 55.5±13.2%; P<0.001 and 11.3±1.7 vs. 17.3±3.3; P<0.05). Serum vascular endothelial growth factor (VEGF) protein at the time of operation and its receptor Flk-1 protein
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Background- Local skin flaps often present with flap necrosis caused by critical disturbance of blood supply. Because hypoxia-inducible factor 1 (HIF-1) has a pivotal role in ischemic vascular responses, we assessed the hypothesis that preoperative stabilization of HIFs using prolyl hydroxylases (PHD) inhibitor contributes to improvement of skin flap survival. Methods and Results- Mice with ischemic skin flap on the dorsum were treated with PHD inhibitor dimethyloxalylglycine (DMOG) 48hr prior to operation by intraperitoneal administration. Immunoblot assay revealed sustained up-regulation of HIF-1α protein at pre- and postoperative states in the skin. Survival area of flap and the number of CD31 positive vessels at proximal part of flaps in DMOG-treated mice were significantly increased at day seven (20.6±4.9% vs. 55.5±13.2%; P<0.001 and 11.3±1.7 vs. 17.3±3.3; P<0.05). Serum vascular endothelial growth factor (VEGF) protein at the time of operation and its receptor Flk-1 protein
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