Polydeoxyribonucleotide restores blood flow in an experimental model of ischemic skin flaps

Autor: Natasha Irrera, Domenica Altavilla, Francesca Polito, Herbert Marini, Mariarosaria Galeano, Francesco Squadrito, Alessandra Bitto, Margherita Calò
Rok vydání: 2012
Předmět:
Male
Vascular Endothelial Growth Factor A
Pathology
Time Factors
Angiogenesis
Dermatologic Surgical Procedures
Nitric Oxide Synthase Type II
PDRN
Surgical Flaps
Rats
Sprague-Dawley
chemistry.chemical_compound
Ischemia
Laser-Doppler Flowmetry
Receptor
Skin
Ultrasonography
biology
VEGF
iNOS
Nitric oxide synthase
Vascular endothelial growth factor
medicine.symptom
Cardiology and Cardiovascular Medicine
Blood Flow Velocity
Injections
Intraperitoneal
medicine.medical_specialty
Adenosine A2 Receptor Agonists
Urology
ischemic skin flaps
Polydeoxyribonucleotides
medicine
Animals
RNA
Messenger
Nitrites
Wound Healing
business.industry
Blood flow
Hypoxia (medical)
medicine.disease
Hypoxia-Inducible Factor 1
alpha Subunit
Rats
Disease Models
Animal
chemistry
Regional Blood Flow
biology.protein
Surgery
Wound healing
business
Zdroj: Journal of Vascular Surgery. 55(2):479-488
ISSN: 0741-5214
DOI: 10.1016/j.jvs.2011.07.083
Popis: 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.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.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.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.
Databáze: OpenAIRE
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