title: Expression of HIF-1 alpha in irradiated tissue is altered by topical negative-pressure therapy.
abstract: OBJECTIVE
  Despite the enormous therapeutic potential of modern radiotherapy, common side effects such as radiation-induced wound healing disorders remain a well-known clinical phenomenon. Topical negative pressure therapy (TNP) is a novel tool to alleviate intraoperative, percutaneous irradiation or brachytherapy. Since TNP has been shown to positively influence the perfusion of chronic, poorly vascularized wounds, the authors applied this therapeutic method to irradiated wounds and investigated the effect on tissue oxygenation in irradiated tissue in five patients.
  
  
  METHODS
  With informed patients' consent, samples prior to and 4 and 8 days after continuous TNP with -125 mmHg were obtained during routine wound debridements. Granulation tissue was stained with hematoxylin-eosin, and additionally with CD31, HIF-1 alpha (hypoxia-inducible factor-1 alpha), and D2-40 to detect blood vessels, measure indirect signs of hypoxia, and lymph vessel distribution within the pre- and post-TNP samples.
  
  
  RESULTS
  In this first series of experiments, a positive influence of TNP onto tissue oxygenation in radiation-induced wounds could be demonstrated. TNP led to a significant decrease of 53% HIF-1 alpha-positive cell nuclei. At the same time, a slight reduction of CD31-stained capillaries was seen in comparison to samples before TNP. Immunostaining with D2-40 revealed an increased number of lymphatic vessels with distended lumina and an alteration of the parallel orientation within the post-TNP samples.
  
  
  CONCLUSIONS
  This study is, to the authors' knowledge, the first report on a novel previously not described histological marker to demonstrate the effects of TNP on HIF-1 alpha expression as an indirect marker of tissue oxygenation in irradiated wounds, as demonstrated by a reduction of HIF-1 alpha concentration after TNP. Since this observation may be of significant value to develop possible new strategies to treat radiation-induced tissue injury, further investigations of HIF-1 alpha regulation under TNP are warranted.
authors.affiliation: Department of Plastic and Hand Surgery, University of Erlangen-Nuremberg, Erlangen, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Grimm
authors.forename: Arno
authors.initials: A
authors.lastname: Dimmler
authors.forename: Sebastian
authors.initials: S
authors.lastname: Stange
authors.forename: Apostolos
authors.initials: A
authors.lastname: Labanaris
authors.forename: Rolf
authors.initials: R
authors.lastname: Sauer
authors.forename: Gerhard
authors.initials: G
authors.lastname: Grabenbauer
authors.forename: Raymund E
authors.initials: RE
authors.lastname: Horch
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D015703:Antigens, CD / Q000032:analysis; D003646:Debridement; D005121:Extremities / Q000601:surgery; D005260:Female; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000032:analysis*; D042601:Lymphatic Vessels / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000032:analysis; D008875:Middle Aged; D009779:Occlusive Dressings; D010101:Oxygen Consumption / Q000528:radiation effects; D011140:Polyurethanes; D011855:Radiodermatitis / Q000473:pathology / Q000628:therapy*; D018714:Radiotherapy, Adjuvant; D012867:Skin / Q000473:pathology; D012883:Skin Ulcer / Q000473:pathology / Q000628:therapy*; D012983:Soft Tissue Neoplasms / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D014618:Vacuum; D014945:Wound Healing / Q000528:radiation effects*
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D015703:Antigens, CD; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C440028:IGSF8 protein, human; D008565:Membrane Proteins; D011140:Polyurethanes; C500987:monoclonal antibody D2-40; C028279:polyurethane foam