title: Polydeoxyribonucleotide restores blood flow in an experimental model of ischemic skin flaps.
abstract: BACKGROUND
  Ischemia is a major factor contributing to failure of skin flap surgery, which is routinely used for coverage of wounds to prevent infection and to restore form and function. An emerging concept is that adenosine A(2A) receptors can improve tissue oxygenation by stimulating angiogenesis, likely through vascular endothelial growth factor (VEGF). This study assessed the ability of polydeoxyribonucleotide (PDRN) to restore blood flow and improve wound healing, acting through the A(2A) receptor, in a rat model of ischemic skin flaps.
  
  
  METHODS
  The H-shaped double-flap model was used in male Sprague-Dawley rats. After surgical procedures, the animals were randomized to receive intraperitoneal PDRN (8 mg/kg) or vehicle (NaCl 0.9%). Rats were euthanized 3, 5, and 10 days after skin injury, after the evaluation of skin perfusion by laser Doppler. The wounds underwent histologic analysis and were measured for VEGF messenger RNA and protein expression, hypoxia inducible factor-1-α (HIF-1α), and inducible nitric oxide synthase (iNOS) protein expression, and nitrite content.
  
  
  RESULTS
  Blood flow markedly increased in blood flow in ischemic flaps treated with PDRN, with a complete recovery starting from day 5 (ischemic flap + vehicle, 1.80 ± 0.25; ischemic flap + PDRN, 2.46 ± 0.25; P < .001). Administration of PDRN enhanced the expression of VEGF (ischemic flap + vehicle, 5.3 ± 0.6; ischemic flap + PDRN, 6.2 ± 0.5; P < .01) at day 5, and iNOS (ischemic flap + vehicle, 3.9 ± 0.6; ischemic flap + PDRN, 5.3 ± 1; P < .01), but reduced HIF-1α expression (ischemic flap + vehicle, 7 ± 1.1; ischemic flap + PDRN, 4.8 ± 0.5; P < .05) at day 3. Histologically, the PDRN-treated group showed complete re-epithelialization and well-formed granulation tissue rich in fibroblasts.
  
  
  CONCLUSIONS
  These results suggest that PDRN restores blood flow and tissue architecture, probably by modulating HIF-1α and VEGF expression, and may be an effective therapeutic approach in improving healing of ischemic skin flaps.
authors: Department of Biochemical, Physiological and Nutritional Sciences, Section of Physiology and Human Nutrition, University of Messina, Messina, Italy.
authors: Francesca
authors: F
authors: Polito
authors: Alessandra
authors: A
authors: Bitto
authors: Mariarosaria
authors: M
authors: Galeano
authors: Natasha
authors: N
authors: Irrera
authors: Herbert
authors: H
authors: Marini
authors: Margherita
authors: M
authors: Calò
authors: Francesco
authors: F
authors: Squadrito
authors: Domenica
authors: D
authors: Altavilla
mesh_terms: D058908:Adenosine A2 Receptor Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001783:Blood Flow Velocity / Q000187:drug effects; D062109:Dermatologic Surgical Procedures; D004195:Disease Models, Animal; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D007274:Injections, Intraperitoneal; D007511:Ischemia / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D017078:Laser-Doppler Flowmetry; D008297:Male; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D011089:Polydeoxyribonucleotides / Q000008:administration & dosage / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects; D012867:Skin / Q000098:blood supply* / Q000000981:diagnostic imaging / Q000378:metabolism; D013524:Surgical Flaps / Q000009:adverse effects*; D013997:Time Factors; D014463:Ultrasonography; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism; D014945:Wound Healing / Q000187:drug effects
chemical_list: D058908:Adenosine A2 Receptor Agonists; C497444:Hif1a protein, rat; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009573:Nitrites; D011089:Polydeoxyribonucleotides; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat