Effect of Vascular Endothelial Growth Factor (VEGF) on Survival of Random Extension of Axial Pattern Skin Flaps in the Rat

Padubidri, Arvind N.; Browne, Earl Z.

doi:10.1097/00000637-199612000-00006

Cited by 98 publications

(59 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…It was speculated that angiogenesis plays an important role in VEGF-165 protein therapy in augmentation of skin flap viability (36,37). However, other investigators reported that local subcutaneous or subdermal injection of VEGF-165 protein into rat skin flaps or musculocutaneous flaps at the time of surgery was also effective in augmenting skin viability (16,19,26,33,47,48). In addition, we demonstrated that intra-arterial infusion of VEGF-165 induced potent relaxation in isolated perfused pig skin flaps (2) and that acute local subcutaneous injection of VEGF-165 increased skin blood flow and viability in rat dorsal skin flaps (16).…”

mentioning

confidence: 99%

Efficacy and mechanism of adenovirus-mediated VEGF-165 gene therapy for augmentation of skin flap viability

Huang¹,

Khan²,

Ashrafpour³

et al. 2006

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

Skin ischemic necrosis due to vasospasm and/or insufficient vascularity is the most common complication in the distal portion of the skin flap in reconstructive surgery. This project was designed to test our hypothesis that preoperative subdermal injection of adenoviral vectors encoding genes for vascular endothelial growth factor-165 (Ad.VEGF-165) or endothelial nitric oxide (NO) synthase (Ad.eNOS) effectively augments skin viability in skin flap surgery and that the mechanism of Ad.VEGF-165 gene therapy involves an increase in synthesis/release of the angiogenic and vasodilator factor NO. PBS (0.5 ml) or PBS containing Ad.VEGF-165, Ad.eNOS, or adenovirus (Ad.Null) was injected subdermally into the distal half of a mapped rat dorsal skin flap (4 × 10 cm) 7 days preoperatively, and skin flap viability was assessed 7 days postoperatively. Local subdermal gene therapy with 2 × 107–2 × 1010 plaque-forming units of VEGF-165 increased skin flap viability compared with PBS- or Ad.Null-injected control ( P < 0.05). Subdermal Ad.VEGF-165 and Ad.eNOS gene therapies were equally effective in increasing skin flap viability at 5 × 108 plaque-forming units. Subdermal Ad.VEGF-165 therapy was associated with upregulation of eNOS protein expression, Ca2+-dependent NOS activity, synthesis/release of NO, and increase in capillary density and blood flow in the distal portion of the skin flap. Injection of the NOS inhibitor Nω-nitro-l-arginine (15 mg/kg im), but not the cyclooxygenase inhibitor indomethacin (5 mg/kg im), 45 min preoperatively completely abolished the increase in skin flap blood flow and viability induced by Ad.VEGF-165 injected subdermally into the mapped skin flap 7 days preoperatively. We have demonstrated for the first time that 1) Ad.VEGF-165 and Ad.eNOS mapped skin flap injected subdermally into the mapped skin flap 7 days preoperatively are equally effective in augmenting viability in the rat dorsal skin flap compared with control, 2) the mechanism of subdermal Ad.VEGF-165 gene therapy in augmenting skin flap viability involves an increase in NO synthesis/release downstream of upregulation of eNOS protein expression and Ca2+-dependent NOS activity, and 3) the vasodilating effect of NO may predominantly mediate subdermal Ad.VEGF gene therapy in augmenting skin flap blood flow and viability.

show abstract

mentioning

confidence: 99%

Efficacy and mechanism of adenovirus-mediated VEGF-165 gene therapy for augmentation of skin flap viability

Huang¹,

Khan²,

Ashrafpour³

et al. 2006

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

show abstract

“…For example, angiogenic growth factors, such as vascular endothelial cell growth factor (VEGF) improved skin flap survival by enhancing the revascularization of ischemic tissues (3,4). VEGF is a specific mitogen for endothelial cells and it stimulates vasculogenesis and angiogenesis.…”

Section: Introductionmentioning

confidence: 99%

“…Considering the fact that HBO could increase the expression of VEGF (9) and both could promote angiogenesis (3,4,10), it was hypothesized that dual treatment of VEGF-loaded microspheres and HBO would result in improved random pattern skin flap survival. To test this hypothesis, the effects of HBO, VEGF loaded microspheres, and HBO plus VEGF on the survival of random skin flaps in rats were analyzed.…”

Section: Introductionmentioning

confidence: 99%

Combination of vascular endothelial growth factor-loaded microspheres and hyperbaric oxygen on random skin flap survival in rats

Xie

Zhang

Dai

et al. 2015

Experimental and Therapeutic Medicine

View full text Add to dashboard Cite

“…In most of these studies, recombinant VEGF provided a beneficial effect on flap survival. [3][4][5][6][7][8][9][10][11][12] Despite these encouraging findings, the use of recombinant proteins in a clinical setting is hampered by several factors, such as their short half-lives, poor bioavailability, and consequent need for frequent administrations to sustain long-lasting effects. The solution to most of these problems may be achieved through gene therapy, which obtains local overexpression of VEGF produced by local cells.…”

mentioning

confidence: 99%

Improved survival of rat ischemic cutaneous and musculocutaneous flaps after VEGF gene transfer

et al. 2007

View full text Add to dashboard Cite

When harvesting microsurgical flaps, the main goals are to obtain as much tissue as possible based on a single vascular pedicle and a reliable vascularization of the entire flap. These aims being in contrast to each other, microsurgeons have been looking for an effective way to enhance skin and muscle perfusion in order to avoid partial flap loss in reconstructive surgery. In this study we demonstrate the efficacy of VEGF 165 delivered by an Adeno-Associated Virus (AAV) vector in two widely recognized rat flap models. In the rectus abdominis myocutaneous flap, intramuscular injection of AAV-VEGF reduced flap necrosis by 50%, while cutaneous delivery of the same amount of vector put down the epigastric flap's ischemia by >40%. Histological evidence of neoangiogenesis (enhanced presence of CD31-positive capillaries and alpha-Smooth Muscle Actin-positive arteriolae) confirmed the therapeutic effect of AAV-VEGF on flap perfusion.

show abstract

Effect of Vascular Endothelial Growth Factor (VEGF) on Survival of Random Extension of Axial Pattern Skin Flaps in the Rat

Cited by 98 publications

References 0 publications

Efficacy and mechanism of adenovirus-mediated VEGF-165 gene therapy for augmentation of skin flap viability

Efficacy and mechanism of adenovirus-mediated VEGF-165 gene therapy for augmentation of skin flap viability

Combination of vascular endothelial growth factor-loaded microspheres and hyperbaric oxygen on random skin flap survival in rats

Improved survival of rat ischemic cutaneous and musculocutaneous flaps after VEGF gene transfer

Contact Info

Product

Resources

About