title: Persistent ischemia impairs myofibroblast development in wound granulation tissue: a new model of delayed wound healing.
abstract: We describe a new animal model designed to assess the impact of ischemia on wound healing. Eight patterns of arterial lesion in the limb were first tested in 24 Wistar rats. Resection of the external iliac artery down to the femoral artery at the level of the knee was chosen as the reference model and performed on the left limb of 45 rats; the right limb was used as the control. Skin wounds measuring 1.2 x 0.8 cm were created on both feet. Ischemia was assessed by blood flow measurement, which decreases dramatically in the ischemic limb. A significant delay in wound closure with a decrease in wound contraction was observed in the ischemic limb. Myofibroblast quantification showed a significant delay in appearance as well as a decrease in the number of these cells in the ischemic wound. Vascular endothelial growth factor-A appearance and evolution were qualitatively similar in both situations. However, collagen type I mRNA was markedly decreased in ischemic granulation tissue 10 days after wounding. These findings suggest that decreased wound contraction plays an important role in delayed ischemic wound healing, probably due to reduced myofibroblast development and activity.
authors.affiliation: Service of Plastic and Reconstructive Surgery, Department of Surgery, Geneva, Switzerland.
authors.forename: Navid
authors.initials: N
authors.lastname: Alizadeh
authors.forename: Michael Sean
authors.initials: MS
authors.lastname: Pepper
authors.forename: Ali
authors.initials: A
authors.lastname: Modarressi
authors.forename: Katia
authors.initials: K
authors.lastname: Alfo
authors.forename: Kai
authors.initials: K
authors.lastname: Schlaudraff
authors.forename: Denys
authors.initials: D
authors.lastname: Montandon
authors.forename: Giulio
authors.initials: G
authors.lastname: Gabbiani
authors.forename: Marie-Luce
authors.initials: ML
authors.lastname: Bochaton-Piallat
authors.forename: Brigitte
authors.initials: B
authors.lastname: Pittet
mesh_terms: D000818:Animals; D015152:Blotting, Northern; D024042:Collagen Type I / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000502:physiology*; D006097:Granulation Tissue / Q000503:physiopathology*; D006614:Hindlimb / Q000098:blood supply; D007124:Immunoenzyme Techniques; D007511:Ischemia / Q000503:physiopathology*; D023421:Models, Animal; D051381:Rats; D017208:Rats, Wistar; D018709:Statistics, Nonparametric; D014945:Wound Healing / Q000502:physiology*
chemical_list: D024042:Collagen Type I