title: Optimization and validation of an ischemic wound model.
abstract: Localized tissue ischemia is a key factor in the development and poor prognosis of chronic wounds. Currently, there are no standardized animal models that provide sufficient tissue to evaluate the effect of modalities that may induce angiogenesis, and in vitro models of angiogenesis do not mimic the complexity of the ischemic wound bed. Therefore, we set out to develop a reproducible ischemic model for use in wound-healing studies. Male Sprague-Dawley rats underwent creation of dorsal bipedicle skin flaps with centrally located excisional wounds. Oxygen tension, wound-breaking strength, wound area, lactate, and wound vascular endothelial growth factor (VEGF) were compared in flaps measuring 2.5 and 2.0 x 11 cm with and without an underlying silicone sheet. We found that the center of the 2.0 cm flap with silicone remains in the critically ischemic range up to 14 days without tissue necrosis (33+/-4 vs. 49+/-6 mmHg in controls). Wound healing and breaking strength were significantly impaired and tissue lactate from the center of this flap was 2.9 times greater than tissue from either nonischemic controls and 2.5 cm flap (0.23+/-0.05 mg/dL/mg sample vs. 0.09+/-0.02 and 0.08+/-0.02, respectively). Vascular endothelial growth factor was 2 times greater than the nonischemic control. This ischemic wound model is relatively inexpensive, easy to perform, reproducible, and reliable. The excisional wounds provide sufficient tissue for biochemical and histologic analysis, and are amenable to the evaluation of topical and systemic therapies that may induce angiogenesis or improve wound healing.
authors.affiliation: Division of Plastic Surgery, Department of Surgery, The University of Texas Medical Branch, Galveston, Texas 77555, USA. ljgould@utmb.edu
authors.forename: Lisa J
authors.initials: LJ
authors.lastname: Gould
authors.forename: Mimi
authors.initials: M
authors.lastname: Leong
authors.forename: Joseph
authors.initials: J
authors.lastname: Sonstein
authors.forename: Shelly
authors.initials: S
authors.lastname: Wilson
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D007511:Ischemia / Q000503:physiopathology*; D008297:Male; D010101:Oxygen Consumption / Q000502:physiology*; D011336:Probability; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D012307:Risk Factors; D012680:Sensitivity and Specificity; D012828:Silicones / Q000494:pharmacology; D012867:Skin / Q000098:blood supply; D013524:Surgical Flaps / Q000098:blood supply*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D014945:Wound Healing / Q000502:physiology*
chemical_list: D012828:Silicones; D042461:Vascular Endothelial Growth Factor A