Skin Flaps In Rats Research Articles

PRP&F/P MPs Improved Survival of Dorsal Paired Pedicle Skin Flaps in Rats

Skin flap necrosis is a problem encountered postoperatively. The purpose of this study was to evaluate the effects of platelet-rich plasma containing fragmin/protamine microparticles (PRP&F/P MPs) on viability in a rat dorsal paired pedicle skin (DPPS) flap. Two symmetrical adjoining rectangular flaps (8 × 2 cm each) were drawn on the rat dorsum. Two days after PRP&F/P MPs-, PRP-, F/P MPs-, and saline (control)-injections (n = 8 each), flaps were elevated as a random pattern flap without the lateral thoracic, posterior intercostal, and deep circumflex iliac vessels. The flaps were immediately sutured back and the flap survival area was measured 7 d after flap elevation. The flap survival rate in PRP&F/P MPs-injected groups (73.1% ± 4.2%) was significantly higher than those in PRP (64.9% ± 4.0%), F/P MPs (59.4 ± 4.5%), and control (61.2% ± 4.2%) groups. Histologic observation of the flaps showed survived thick granulation tissue and neovascularization in PRP&F/P MPs-injected groups. When PRP&F/P MPs are administered 2 d before the flap elevation, the improved flap survivals are observed. The pre-injection of PRP&F/P MPs may thus represent a promising treatment to prevent skin flap necrosis in reconstructive surgery.

Thermography‐measured effect of capsaicin, methylprednisolone and mitomycin on the survival of random skin flaps in rats

This study was designed to determine if steroids, capsaicin and mitomycin improved skin flap survival in rats, and it has confirmed that thermography is an effective method to measured skin flap vitality. Forty female Wistar rats were randomised into four groups. A standardised full thickness inferiorly based dorsal random-pattern skin flap was raised, and a gelatine sponge was placed before suturing between the flap and its recipient bed, soaked with 0.9 % saline in the control group and with capsaicin, methylprednisolone and mitomycin in the experimental groups. Vitality of the flap and of the survival area was measured by infrared thermography. Methylprednisolone statistically significant decrease skin flap necrosis, approximately 56%, when compared with controls (P< 0.05). Corticosteroids applied subcutaneously in a single dose on a gelatine sponge produced a statistically significant improvement of the survival of random skin flaps in rats, whereas capsaicin and mitomycin showed no improvement.

Low-Level Laser Therapy on the Viability of Skin Flap in Rats Subjected to Deleterious Effect of Nicotine

The purpose of this study was to evaluate the effect of 830-nm laser in blocking the action of nicotine on the viability of skin flap. The authors have analyzed the deleterious effect of cigarette smoke or nicotine on the skin flap alone with evidence of increased skin necrosis in the flap. Twenty-four Wistar-albino rats were divided into three groups of eight animals each: Group 1 (control), subjected to a surgical technique to obtain a flap for cranial base, laser irradiation simulation, and a subcutaneous injection of saline; Group 2, similar to Group 1, with subcutaneous injection of nicotine (2 mg/kg/day) for a period of 1 week before and 1 week after surgery; and Group 3, similar to Group 2, with skin flaps subjected to a λ 830-nm laser irradiation. The laser parameters used were: power 30 mW, beam area 0.07 cm(2), irradiance 429 mW/cm(2), irradiation time 84 sec, total energy 2.52 J, and energy density 36 J/cm(2). The laser was used immediately after surgery and for 4 consecutive days, in one point at 2.5 cm of the flap cranial base. The areas of necrosis were examined by two macroscopic analyses: paper template and Mini-Mop(®). The pervious blood vessels were also counted. The results were statistically analyzed by ANOVA and post-test contrast orthogonal method (multiple comparisons), showing that the laser decreased the area of necrosis in flaps subjected to nicotine, and consequently, increased the number of blood vessels (p < 0.05). The laser proved to be an effective way to decrease the area of necrosis in rats subjected to nicotine, making them similar to the control group.

Quantitative regression analysis of the cutaneous vascular territories in a rat model

The rat skin flap model has been widely used in experimental flap survival studies; however, most of these have been qualitative studies. The purpose of this study was to investigate the quantitative relationship between the diameter of a cutaneous artery and the area of skin that it supplies, and also to explore the factors that influence this relationship. Thirty rats were injected with lead oxide and gelatin and then radiographed. Computer imaging of the diameter and the area of blood supply of the cutaneous artery were made to investigate the mathematical relationship between the arterial diameter and its perfusion area. Angiograms were assembled using Adobe Photoshop and analyzed with Scion Image and SPSS software. The blood vessels had an average diameter of 0.53 ± 0.12 mm, perimeter of 18.74 ± 4.84 cm, vascular density of 391.31 ± 76.58 gray value/pixel cm, vascular territory of 22.32 ± 10.04 cm(2) and supplying volume of 4.88 ± 3.02 cm(3). There was a positive correlation between the diameter and the perimeter of the vascular territory, and the area and volume of the vascular territory. The linear regression equation was y = 32.44x + 1.23 [y: nutrition region perimeter (cm), x: cutaneous artery diameter (mm)], y = 72.70x-15.93 [y: supplying area (cm(2)), x: cutaneous artery diameter (mm)] and y = 20.36x-5.83 [y: supplying volume (cm(3)), x: cutaneous artery diameter (mm)], respectively. Based on this data, it is postulated that the size of reliable skin flaps can be calculated by the diameter and the distribution patterns of the cutaneous artery. With the same diameter, the area of the flap supplied by branch-style artery is larger than the one supplied by the axial artery.

Laser 830nm na viabilidade do retalho cutâneo de ratos submetidos à nicotina

OBJETIVO: Investigar os possíveis efeitos da laserterapia com laser diodo 830nm ao se contrapor a ação da nicotina na viabilidade do retalho cutâneo em ratos. MÉTODOS: Foram utilizados 16 ratos Wistar, distribuídos em 2 grupos de 8: Grupo 1- submetido à técnica cirúrgica, para obtenção dos retalhos cutâneos randômicos de base cranial, com injeção subcutânea de nicotina em uma dose de 2mg/Kg/dia, uma semana antes e uma semana após o procedimento cirúrgico e simulação da radiação laser; Grupo 2- similar ao grupo 1, cujos retalhos cutâneos randômicos de base cranial foram submetidos à irradiação do laser imediatamente após a cirurgia e nos 4 dias subsequentes. Após a eutanásia, as áreas de necrose e de tecido viável foram examinadas através do método de pesagem do Gabarito de Papel e pelo método semi-automático de análise de imagens (Mini-Mop®). RESULTADOS: Os resultados foram analisados estatisticamente através do teste ANOVA. Os valores de porcentagem de área de necrose através do método de análise mostraram uma diminuição da área de necrose no grupo 2 onde foi aplicado laser. CONCLUSÃO: O laser 830nm foi eficaz na melhora da viabilidade do retalho cutâneo em ratos submetido à ação da nicotina. Nível de evidência II: Estudos terapêuticos - Investigação dos resultados do tratamento.

Preoperative shock wave treatment enhances ischemic tissue survival, blood flow and angiogenesis in a rat skin flap model

Introduction Extracorporeal shock wave treatment (ESWT) has recently been shown to enhance skin flap survival. However, the bio-mechanisms operating during preoperative ESWT remain unclear. The aim of our study was to investigate whether preoperative ESWT can improve blood flow in ischemic skin flaps and to elucidate its possible mechanisms. Methods 14 male-rats were randomized into two groups and an oversized ventral random-pattern flap was raised. Experimental group received extracorporeal shock-wave treatment (ESWT) with an energy of 500 mJ/mm 2 seven days prior to total flap elevation, while control group received no treatment prior to total flap elevation. Seven days postoperatively, surviving flap area, perfused flap area, microvessel density and VEGF concentration were measured. Results Surviving flap area (59.43 ± 14.72 % to 42.71 ± 10.75 %, p = 0.026), perfused flap area (62.00 ± 8.58 % to 45.14 ± 10.50 %, p = 0.007), microvessel density (18.13 ± 5.11 to 11.09 ± 1.12, p = 0.016) and VEGF to total protein ratio (0.2107 ± 0.0935 to 0.0123 ± 0.0069, p = 0.008) were significantly elevated in the ESWT group. Conclusion Preoperative ESWT can improve skin flap survival through enhanced topical blood perfusion and neovascularization via elevation of angio-active factors.

Microencapsulated Myoblasts Transduced by the Vascular Endothelial Growth Factor (VEGF) Gene for the Ischemic Skin Flap

This experimental study aimed to explore the influence of locally administered microencapsulated vascular endothelial growth factor (VEGF)-secreting myoblasts on the survival of the ischemic skin flap in rats and to elucidate the underlying molecular mechanism. The pcDNA6/His A-VEGF165 plasmid was constructed, amplified, and transfected into myoblasts. Cells then were encapsulated in a sodium alginate-barium chloride microcapsule. The study investigated 64 Wistar rats (males and females). Two symmetric 2×10-cm, full-thickness dorsal ischemic skin flaps were elevated on each rat. One flap was used as the experiment area, and the other was used as a control. The microencapsulated VEGF-secreting myoblasts were injected into the right flap of the rat on preoperative days 0, 2, 4, and 7. The left flap in each animal was injected with the encapsulated untransfected cells. The 64 rats were randomly divided into four groups of 16 rats each. The effect of the experimental group was significantly better than that of the control group. The experimental group had a certain time-dependent effect. Microencapsulated VEGF-secreting-myoblasts may be a promising therapy for ischemic flaps in rats.

Mechanical Stimulation Improves Survival in Random-Pattern Skin Flaps in Rats

This was a study on the effects of 3-MHz ultrasound at 16- and 100-Hz pulse repetition frequencies on angiogenesis and viability of random-pattern skin flaps in rats. A cranially-based dorsal skin flap was raised in 60 EPM-Wistar rats, which were randomly divided into four groups: control, sham, 16-Hz and 100-Hz groups. The mean percentage of necrosis was as follows: control, 42% ± 13%; sham, 18% ± 13%; 16-Hz group, 13% ± 10%; and 100-Hz group, 15% ± 7%, with significant differences between the control and the other groups ( p < 0.001). The mean vascular density was as follows: control, 5% ± 2%; sham, 7% ± 2%; 16-Hz group, 21% ± 4%; and 100-Hz group, 24% ± 10%, with significant differences between control and ultrasound groups, and between the sham and ultrasound groups ( p < 0.001). Both ultrasound treatments (16- and 100-Hz PRFs) induced angiogenesis, and sham and ultrasound treatments improved viability of random-pattern skin flaps in rats. (E-mails: pascale.tacani@hotmail.com; sandra.dcir@epm.br)

Capsaicin on the viability of random-pattern skin flaps in rats

To evaluate the effects of capsaicin on the viability of ischemic random-pattern skin flaps in rats. Forty EPM1-Wistar rats were randomized into two groups of 20 animals each, the capsaicin group and the control group. A random-pattern skin flap measuring 10 x 4 cm was raised and a plastic barrier was placed between the flap and the donor site. After the surgical procedure, the control group was treated with an inert vehicle in the form of a cream applied uniformly to a rayon bandage which, in turn, was applied to the surface of the skin flap. The capsaicin group was treated in the same way, but in this case capsaicin was added to the cream. This procedure was repeated for two consecutive days. There was a significantly smaller amount of flap necrosis in the capsaicin group (35.07%) than in the control group (44.75%) (p=0.035). Topical administration of capsaicin improved the viability of ischemic random-pattern skin flaps in rats.

Vasorelaxation Effect and Mechanism of Action of Vascular Endothelial Growth Factor-165 in Isolated Perfused Human Skin Flaps

Experimental evidence is accumulating to indicate that local acute vascular endothelial growth factor-165 (VEGF(165)) therapy is effective in attenuation of skin ischemia and increase in skin viability in rat skin flap surgery and the mechanism involves vasodilation induced by VEGF(165). So far, the vasodilator effect and mechanism of action of VEGF(165) have not been studied in human skin. The objective of this project is to test the hypothesis that VEGF(165) is also a potent vasodilator in human skin vasculature. We used an established isolated perfused human skin flap model and pharmacologic probes to demonstrate that VEGF(165) is a potent vasodilator in human skin vasculature and the mechanism involves activation of receptors and postreceptor signaling pathway, which in turn stimulates local synthesis/release of endothelial vasodilators. We observed that VEGF(165) induced a concentration-dependent vasorelaxation in human skin flaps preconstricted with norephinephrine (8 × 10(-7)M; n = 7) or endothelin-1 (3 × 10(-9)M; n = 6). The vasorelaxation potency of VEGF(165) (pD(2) = 12.02 ± 0.25; n = 7) was higher (P < 0.05) than that of acetylcholine (pD(2) = 6.76 ± 0.06; n = 5) in human skin flaps preconstricted with 8 x 10(-7)M of norepinephrine. Using pharmacologic probes, we also detected that the vasorelaxation effect of VEGF(165) in the isolated perfused human skin flaps (n = 4) was triggered by activation of VEGF receptor-2. Furthermore, the postreceptor signaling pathway involved activation of Src family tyrosine kinase, phospholipase C, protein kinase C, an increase in inositol 1,4,5-triphosphate activity, a release of the intracellular Ca(2+) store, and finally synthesis/release of the endothelial nitric oxide (eNO) and prostacyclin and eNO predominantly mediated the vasodilator effect of VEGF(165) in the effector mechanism. These findings support our hypothesis that VEGF(165) is a potent vasodilator in human skin vasculature and also provide important insights into the clinical study of local acute VEGF(165) therapy for prevention/treatment of skin ischemia in skin flap surgery.

Enhancement of ischemic wound healing by inducement of local angiogenesis

To determine if monocytes activated toward an angiogenic phenotype can be used to improve ischemic tissue healing in a rat skin flap model. Prospective experimental study on Wistar rats. A caudally based 9 x 3 cm dorsal skin/panniculus carnosus flap was raised in 15 rats. The animals were divided into three groups: the monocyte group (N = 5) received subcutaneous topical application of 0.1-0.2 cc of i-Monogrid, a collagen gel containing M2 angiogenic monocytes; control group 1 (N = 5) received application of cell-free collagen; and control group 2 (N = 5) received no treatment. Skin flaps were stapled in place and observed for wound ischemia and necrosis of the skin flap. One week postoperatively, skin and underlying muscle were harvested for histologic analyses. No macroscopic differences in wound healing or microscopic differences in skin viability were observed. However, the monocyte group showed significantly greater vascular improvement than C1 (P = .047, chi = 3.96), and a trend toward greater vascular improvement than C2 (P = .103, chi = 2.67). Delivery of activated pro-angiogenic monocytes to an ischemic skin flap tended to improve histologic evidence of vascularity without corresponding microscopic or gross evidence of improved flap survival. These results are encouraging regarding the use of monocytes as a potential method of improving vascularization of ischemic tissue.

Effects of Pentoxyfilline and Heparin on Reperfusion Injury Island Skin Flaps in Rats Exposed to Tobacco

Ischemia-reperfusion injury is believed to be a major cause of transferred skin flap failure. Cigarette smoking is known to be associated with endogenous antioxidant depletion, hypercoagulability, and cutaneous vasoconstriction. This investigation was carried out to study possible effects of pentoxyfilline or heparin on rat skin reperfusion injury under tobacco exposure. Thirty-six rats were randomized into two major groups: 18 were exposed to cigarette smoke during a 4 wk period prior to surgery; the remaining 18 underwent a sham smoking procedure. Each group was further divided into three equal subgroups: heparin, pentoxyfilline, and saline solution. One identical skin flap was raised in each animal. The vasculature of the flap was clamped for 3 h and reperfused for 5 min. A venous blood sample was obtained from the flap after reperfusion for serum malondialdehyde (MDA) and myeloperoxidase (MPO) analysis. Flap survival was assessed 7 d after the procedure. The lipid peroxidation levels and flap necrosis were significantly higher in the cigarette-smoking group skin flaps. There was also a decrease of MPO activity in this group compared with the non-smoking group. Heparin-treated rats had significantly lower MDA levels and showed the most viable percent area among smoking rats. These data suggest that heparin had a significant beneficial effect both on flap survival and on the lipid peroxidation reduction after smoke exposure in the rat axial-pattern skin flap subjected to ischemia and reperfusion injury. Pharmacologic therapy may represent an alternative way to counteract tobacco effects in flap surgery in emergency situations.

Effect of Low-Level Laser Therapy with Output Power of 30 mW and 60 mW in the Viability of a Random Skin Flap

To assess the effects of low-level laser therapy (LLLT) with output power of 30 and 60 mW in the viability of a random skin flap in rats. Output power values in LLLT are not well defined. Controlled, single-blind experimental study. Thirty-six animals were randomly distributed into three groups: sham group (SG), 30-mW output power (30G), and 60-mW output power (60G). In both treated groups, a fluency of 3 J/cm(2) was used. Two minutes after elevation of a random-pattern cranially based dorsal flap (4 x 10 cm), laser irradiation was applied and repeated on the first, second, third, and fourth postoperative days. Percentages of flap necrosis were calculated on the seventh postoperative day. Also, four fragments of each flap were collected to allow determination of the percentages of vascular density according to the bidimensional method of the morphometric analysis of blood vessels. Statistical analysis included the Wilcoxon test and Kruskal-Wallis variance analysis. A significance level of 5% was elected (p < 0.05). Laser-treated animals presented significantly less necrosis than the sham group (SG, 53%; 30G, 24%; p < 0.05) (60G, 25%; p < 0.05). Also, laser-treated animals presented significantly more vascular density than the sham group (SG, 37%; 30G, 57%; p < 0.05) (60G, 59%; p < 0.05). LLLT (660 nm) with 30-mW and 60-mW output power was efficient in the increase of skin flap viability, but there was no difference between them.

A new design of a dorsal flap in the rat to study skin necrosis and its prevention

The Mcfarlane flap or dorsal pedicled flap has become the standard model for pedicled rat skin flap study but its reliability has been called to question. In the past, there were possible confounding variable with the McFarlane flap and various methods were used to adjust these variables. We have developed a new model for studying skin flap necrosis and its prevention that eliminates these confounding variables. The flap is a significant modification of the McFarlane flap where we form a blind ended pedicled tube using a 3 cm x 9 cm dorsal flap. Survival area is measured using digital photography and computer assisted analysis. This new flap is compared with the standard McFarlane flap with n=25 in each group. The mean survival area of the new flap (15.673 cm(2)+SD3.37) is comparable with the McFarlane flap (18.904 cm(2)+SD3.79). The relative merit lies in the elimination of the confounding variable of the graft bed influence on our flap without a significant reduction in the survival area. A new rat model is presented that may be used in studying the effect of various treatment modalities on pedicled skin flaps. This model has the benefit of eliminating graft bed effect without the risk of flap and wound infection or desiccation that have been encountered using other models. The new flap also has better demarcation of necrosis area in this study.

The Effects of 660 nm and 780 nm Laser Irradiation on Viability of Random Skin Flap in Rats

Some studies have shown that laser phototherapy is able to increase skin flap viability by decreasing the necrotic area and increasing neoangiogenesis. However, the mechanism by which laser acts on cells is not fully understood. The present study investigated the effects of two different laser wavelengths at 30 and 40 J/cm(2) on the viability of skin flap in rats. Sixty male animals were used in this study. They were distributed into the following groups (n = 12 each group): control group, group irradiated with 660 nm at 30 J/cm(2); group irradiated with 780 nm, at 30 J/cm(2), group irradiated with 660 nm at 40 J/cm(2); and group irradiated with 780 nm at 40 J/cm(2). The skin flap was performed on the back of all animals studied, with a plastic sheet interposed between the flap and the donor site. Laser irradiation was done immediately after the surgery and on days 1, 2, 3, and 4 post-surgery. The percentage of the necrotic area of the flap was calculated at day 7 post-surgery. Control group showed a necrotic area of 62.83%. Interestingly, no statistically significant differences were found among the treated groups and the control group. This present study showed that 660 nm and 780 nm lasers at doses of 30 and 40 J/cm(2) were not effective for decreasing the necrotic area of the skin flaps in rats.

Effect of Application Site of Low-Level Laser Therapy in Random Cutaneous Flap Viability in Rats

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.

The effect of botulinum toxin A on skin flap survival in rats

This study examines the role of botulinum toxin type A (BoTA) in preventing the collapse of the peripheral vessels in the cutaneous flap and in increasing the survival of the flap. Because BoTA cleaves the SNAP-25 protein, the release of vasoconstriction cotransmitters as well as acetylcholine would be blocked. Dorsal skin flaps in rats were elevated and returned to the original position. In the BoTA and the control group, either BoTA or saline was injected into the entire flap. The flap survival rate measurement and a histopathological examination were performed 1 week after flap elevation. The cutaneous blood flow was measured in three different areas of each flap, serially. In BoTA group, there was a significant increase in the survival rate (93.79 +/- 6.06%, p=0.042). In the control group, the blood flow was decreased significantly immediately after flap elevation. The blood flow was high in all areas in the BoTA group in a week, and also most of the vessels maintained their shape without collapsing. In conclusion, pretreatment with BoTA increases the dorsal skin flap survival in rats by increased perfusion, and further studies should be performed to determine the possible mechanism by which BoTA attenuates the sympathetic vasoconstriction effect in skin flaps.

The Effects of the Pentoxifylline on Survival of the Skin Flaps in Streptozotocin-Diabetic Rats

Skin flaps are frequently performed for diabetic patients in spite of countless detrimental effects of diabetes on flap survival. This study was planned because only a few clinical experiments have been performed on the effect of pentoxifylline (PTX) on the flaps in diabetic-animals. We studied 4 groups of rats: group 1, diabetic PTX treatment; group 2, diabetic control; group 3, nondiabetic PTX treatment; group 4, nondiabetic control. For the diabetic groups, diabetes mellitus was induced via intraperitoneal injection of streptozotocin (55 mg/kg). For treatment groups, PTX injections were started at the end of the 6th week of the experiment and procedures were carried out for 4 weeks during the experiment. Modified McFarlane flaps were elevated from all animals at the end of the 10th week of the experiment. Surviving areas of the flaps were measured at the end of the 11th week. Flap survival of the nondiabetic control and diabetic PTX treatment groups were significantly higher than of the diabetic control group (P < 0.01). Also, flap survival of the diabetic PTX treatment group was not statistically different than of the nondiabetic control group, but flap survival of the nondiabetic PTX treatment group was not statistically different from that of the nondiabetic control group. PTX appears to help decrease the harmful effects of diabetes on survival of the skin flaps.

Intradermal Delivery of Plasmid VEGF165 by Electroporation Promotes Wound Healing

Skin flaps are extensively used in reconstructive surgeries to repair large defects and deep wounds, but severe ischemia and necrosis often results in loss of the transplanted tissue. Thus, skin flap models are often used to study the biology of healing and necrosis of acute ischemic wounds. Delivery of exogenous vascular endothelial growth factor (VEGF) to areas of ischemia has shown promise for promoting therapeutic angiogenesis, but its expression must be tightly regulated to avoid adverse effects. In this study, plasmid DNA encoding VEGF(165) (pVEGF) was delivered to the ischemic skin of a rat skin flap model by intradermal injection followed by electroporation (EP) (pVEGFE+). Treatment with pVEGFE+ significantly increased VEGF expression for 5 days after delivery compared to injection of pVEGF without EP (pVEGFE-). The short-term increase in VEGF was sufficient to mediate an upregulation of endothelial nitric oxide synthase, an angiogenic factor that increases vascular permeability. pVEGFE+ significantly increased skin flap perfusion at both days 10 and 14 postoperatively. The observed increase in perfusion with pVEGFE+ correlated with an increase in skin flap healing and survival. Our results demonstrate that pVEGFE+ is a potential nonviral noninvasive therapy to increase perfusion and healing of skin flaps and ischemic wounds.

Histamine iontophoresis on the viability of random skin flap in rats

To evaluate the effects of the histamine iontophoresis on the random skin flap viability in rats. Sixty adult male Wistar rats were used. A cranially-based dorsal skin flap measuring 10 x 4 cm was raised and a plastic barrier was placed between the flap and its bed. After the surgical procedure, the animals were randomized into four groups (G1-G4) (n=15 each group) as follows: G1 (control)--sham electrical stimulation, G2 (electrical stimulation)--direct current electrical stimulation, G3 (histamine)--histamine and sham electrical stimulation, and G4 (histamine iontophoresis)--transdermal iontophoresis of histamine. In all groups the procedures were performed immediately after the surgery and on the two subsequent days. The percentage of flap necrosis was measured on the seventh postoperative day. The mean and the respective standard deviation of the percentage of flap necrosis areas were as follows: G1 (control) - 47.87 +/- 9.13%, G2 - 51.49 +/- 8.19%, G3 - 46.33 +/- 8.32% and G4 - 30.82 +/- 11.25%. The G4 group presented a significantly smaller amount of flap necrosis when compared to the other groups (p<0.001). The topical administration of the histamine by iontophoresis was effective to increase the viability of the random skin flaps in rats.