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

Department of Biochemical, Physiological and Nutritional Sciences, Section of Physiology and Human Nutrition, University of Messina, Messina, Italy.
Journal of vascular surgery: official publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter (Impact Factor: 3.02). 11/2011; 55(2):479-88. DOI: 10.1016/j.jvs.2011.07.083
Source: PubMed


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.

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    • "Stimulation of the A2A receptor induces activation of a G protein leading to cyclic AMP (cAMP) signaling, activation of protein kinase A, and cell proliferation [16]. In previous studies, PDRN was used as an angiogenesis stimulator and wound healing agent in diabetic mice [9]; in cases of thermal injury [18], it has been shown to improve blood flow in peripheral artery occlusive disease in rats [13], enhances the growth rate of human fibroblasts and osteoblasts in in vitro models [19], and restores blood flow in ischemic skin flaps [20]. In addition, PDRN has been shown to stimulate corneal epithelium regeneration after photorefractive keratectomy and myopic stigmatic defects [21] and accelerates the wound healing of graft donor sites [22,23]. "
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    ABSTRACT: This study aimed to investigate the effect of diode laser (830 nm) irradiation on the viability of ischemic random skin flaps in rats, as well as to determine the most effective site for applying laser radiation to speed healing. Low-level laser therapy (LLLT) has recently been used to improve the viability of ischemic random skin flaps in rats. Seventy Wistar rats were used and divided into seven groups of 10 rats each: group 1, sham laser treatment; group 2, which received irradiation at 1 point 5 cm from the flap's cranial base; group 3, which received irradiation at 2 points (5 and 7.5 cm from the flap's base); group 4, which received irradiation at 3 points (2.5, 5 and 7.5 cm from the flap's base); group 5, which received irradiation at 1 point 2.5 cm from the flap's base; group 6, which received irradiation at 2 points (2.5 and 5 cm from the flap's base); and group 7, which received irradiation at 1 point 7.5 cm from the flap's base. The animals were subjected to laser therapy at an energy density of 36 J/cm(2) for 72 sec immediately after surgery, and one time on each of the four subsequent days. The percentage of necrotic skin flap area was calculated on the seventh postoperative day using a paper template. The results showed that the rats in group 5 had the highest increase in skin flap viability, with a statistically significant difference compared to the other groups. Statistically significant differences were not seen between any of the other groups. The diode laser was effective in increasing skin flap viability in rats, and laser irradiation of a point 2.5 cm from the cranial base flap was found to be the most effective.
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