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: Francesca Polito, Alessandra Bitto, Mariarosaria Galeano, Natasha Irrera, Herbert Marini, Margherita Calò, Francesco Squadrito, Domenica Altavilla
• Journal: Journal of vascular surgery (J Vasc Surg) Vol. 55 Issue 2 Pg. 479-88 (Feb 2012) ISSN: 1097-6809 [Electronic] United States
• PMID: 22051873 (Publication Type: Journal Article)
• Copyright: Copyright © 2012 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.

Chemical References

• Adenosine A2 Receptor Agonists
• Hif1a protein, rat
• Hypoxia-Inducible Factor 1, alpha Subunit
• Nitrites
• Polydeoxyribonucleotides
• RNA, Messenger
• Vascular Endothelial Growth Factor A
• vascular endothelial growth factor A, rat
• Nitric Oxide Synthase Type II
• Nos2 protein, rat

Topics

• Adenosine A2 Receptor Agonists (administration & dosage, pharmacology)
• Animals
• Blood Flow Velocity (drug effects)
• Dermatologic Surgical Procedures
• Disease Models, Animal
• Hypoxia-Inducible Factor 1, alpha Subunit (metabolism)
• Injections, Intraperitoneal
• Ischemia (diagnostic imaging, drug therapy, etiology, metabolism, physiopathology)
• Laser-Doppler Flowmetry
• Male
• Nitric Oxide Synthase Type II (metabolism)
• Nitrites (metabolism)
• Polydeoxyribonucleotides (administration & dosage, pharmacology)
• RNA, Messenger (metabolism)
• Rats
• Rats, Sprague-Dawley
• Regional Blood Flow (drug effects)
• Skin (blood supply, diagnostic imaging, metabolism)
• Surgical Flaps (adverse effects)
• Time Factors
• Ultrasonography
• Vascular Endothelial Growth Factor A (genetics, metabolism)
• Wound Healing (drug effects)