Viability Of Random Skin Flaps Research Articles

Activation of aldehyde dehydrogenase-2 improves ischemic random skin flap survival in rats.

Random skin flaps have many applications in plastic and reconstructive surgeries. However, distal flap necrosis restricts wider clinical utility. Mitophagy, a vital form of autophagy for damaged mitochondria, is excessively activated in flap ischemia/reperfusion (I/R) injury, thus inducing cell death. Aldehyde dehydrogenase-2 (ALDH2), an allosteric tetrameric enzyme, plays an important role in regulating mitophagy. We explored whether ALDH2 activated by N-(1,3-benzodioxol-5-ylmethyl)-2,6-dichlorobenzamide (Alda-1) could reduce the risk of ischemic random skin flap necrosis, and the possible mechanism of action. Modified McFarlane flap models were established in 36 male Sprague-Dawley rats assigned randomly to three groups: a low-dose Alda-1 group (10 mg/kg/day), a high-dose Alda-1 group (20 mg/kg/day) and a control group. The percentage surviving skin flap area, neutrophil density and microvessel density (MVD) were evaluated on day 7. Oxidative stress was quantitated by measuring the superoxide dismutase (SOD) and malondialdehyde (MDA) levels. Blood perfusion and skin flap angiogenesis were assessed via laser Doppler flow imaging and lead oxide-gelatin angiography, respectively. The expression levels of inflammatory cytokines (IL-1β, IL-6, and TNF-α), vascular endothelial growth factor (VEGF), ALDH2, PTEN-induced kinase 1 (PINK1), and E3 ubiquitin ligase (Parkin) were immunohistochemically detected. Indicators of mitophagy such as Beclin-1, p62, and microtubule-associated protein light chain 3 (LC3) were evaluated by immunofluorescence. Alda-1 significantly enhanced the survival area of random skin flaps. The SOD activity increased and the MDA level decreased, suggesting that Alda-1 reduced oxidative stress. ALDH2 was upregulated, and mitophagy-related proteins (PINK1, Parkin, Beclin-1, p62, and LC3) were downregulated, indicating that ALDH2 inhibited mitophagy through the PINK1/Parkin signaling pathway. Treatment with Alda-1 reduced neutrophil infiltration and expressions of inflammatory cytokines. Alda-1 significantly upregulated VEGF expression, increased the MVD, promoted angiogenesis, and enhanced blood perfusion. ALDH2 activation can effectively enhance random skin flap viability via inhibiting PINK1/Parkin-dependent mitophagy. Moreover, enhancement of ALDH2 activity also exerts anti-inflammatory and angiogenic properties.

THE EFFECT OF ORALLY ADMINISTERED COENZYME Q10 ON THE VIABILITY OF RANDOM SKIN FLAP IN NICOTINE EXPOSED WISTAR RATS

Introduction : Nicotine was assumed to be the cause of compromised flap. The administration of antioxidants can eliminate such effect, and one of the most promising antioxidants is Coenzyme Q10. The research aims to find the effect of orally administered Coenzyme Q10 on the viability of random skin flaps in nicotine-exposed wistar rats. Method : Twenty-seven white rats (Rattus norvegicus) were assigned in three groups. The first group received no nicotine, while the other two groups were nebulized with nicotine for 4 consecutive weeks, and treated as random skin flaps. In third group, Coenzyme Q10 was administered for 7 days. Then, a standard histopathological staining and vascular endothelial growth factor (VEGF) measurement were performed on flap sample to examine the extent of neovascularization and VEGF cell expression. Result : The average number of capillaries in group I was 5.33 ± 1.323, in group II was 5.89 ± 0.782, and in group III was 7.78 ± 2.587. There was no significant difference (p = 0.317, 95% CI) in groups I and II of VEGF expression. However, significant differences were found in the intensity of VEGF (p = 0.009, 95% CI) in groups I and group III, and in groups II and group III (p = 0.011, 95% CI). Thus, the intensity was stronger on the subject with coenzyme Q10 compared with the other two groups. Conclusion: Coenzyme Q10 increases the viability of random flaps by increasing the number of capillaries and VEGF expression.

Edaravone promotes viability of random skin flaps via activating PI3K/Akt/mTOR signalling pathway-mediated enhancement of autophagy.

Random skin flap transplantation is a commonly used technique. However, ischemia and ischemia-reperfusion injury always impair its therapeutic effectiveness through acclerating oxidative stress, apoptosis and suppressing angiogenesis. To survive, cells rely on mediating autophagy, DNA repair, immunoregulation to resist these cellular injuries. Thus, mediating autophagy may affect the survival of random skin flaps. The edaravone (EDA), a oxygen radicals scavenger, also possesses autophagy mediator potential, we investigated the effects of EDA on skin flap survival and its autophagy-related mechanisms. In vivo, mice were administered EDA or saline intraperitoneally for 7 days postoperatively. We found that EDA ameliorated the viability of random skin flaps, promoted autophagy and angiogenesis, attenuated apoptosis and oxidative stress. In vitro, mouse umbilical vascular endothelial cells (MUVECs) were administered EDA or 3-methyladenine (3-MA, an autophagy inhibitor) or rapacymin (Rapa, an autophagy activator) at the beginning of oxygen glucose deprivation (OGD). We found that EDA promoted cell viability, activated autophagy, enhanced angiogenesis, alleviated apoptosis and oxidative stress. On one hand, 3-MA reversed the effects of EDA on cell viability, oxidative stress and apoptosis via inhibiting autophagy. On the other hand, Rapa had the similar effects of EDA. Furthermore, EDA-induced autophagy was mediated through downregulating PI3K/Akt/mTOR signalling pathway. The findings showed that EDA ameliorated viability of random skin flaps by promoting angiogenesis, suppressing oxidative stress and apoptosis, which may be mediated by autophagic activation through downregulating PI3K/AKT/mTOR signalling pathway.

Berberine promotes the viability of random skin flaps via the PI3K/Akt/eNOS signaling pathway.

Random skin flaps are often used in reconstruction operations. However, flap necrosis is still a common postoperative complication. Here, we investigated whether berberine (C20 H19 NO5 , BBR), a drug with antioxidant activity, improves the survival rate of random flaps. Fifty-four rats were divided into three groups: control, BBR and BBR +L -NAME groups (L -NAME, L -NG -Nitro-arginine methyl ester). The survival condition and the percentage of survival area of the flaps were evaluated on the seventh day after surgery. After animals were sacrificed, angiogenesis, apoptosis, oxidative stress and inflammation levels were assessed by histological and protein analyses. Our findings suggest that berberine promotes flap survival. The level of angiogenesis increased; the levels of oxidative stress, inflammation and apoptosis decreased; the levels of phosphoinositide 3-kinase (PI3K), phospho-Akt (p-Akt) and phospho-endothelial nitric oxide synthase (p-eNOS) increased in the flap tissue; and L -NAME reversed the effects of berberine on random skin flaps. Statistical analysis showed that the BBR group results differed significantly from those of the control and the BBR +L -NAME groups (p< .05). Our results confirm that berberine is an effective drug for significantly improving the survival rate of random skin flaps by promoting angiogenesis, inhibiting inflammation, attenuating oxidative stress, and reducing apoptosis through the PI3K/Akt/eNOS signaling pathway.

Catalpol Enhances Random-Pattern Skin Flap Survival by Activating SIRT1-Mediated Enhancement of Autophagy.

Random-pattern skin flap necrosis limits its application in the clinic. It is still a challenge for plastic surgeons. Catalpol is an effective ingredient extracted from Rehmannia glutinosa, which is reported to promote angiogenesis and protect against ischemic cerebral disease. The aim of our experiment is to assess whether catalpol can facilitate random flap survival and the underlying mechanisms. Male “McFarlane flap” rat models were employed to explore the protective effects of catalpol. The range of necrosis in the flap was calculated 7 days after the models were established. The flap specimens were harvested for further experiments, including angiogenesis, apoptosis, oxidative stress, and autophagy evaluation. Catalpol-treated group promoted the average survival area of the flap than that in the control group. Based on immunohistochemical staining, Western blotting, and ROS detection, we found that catalpol significantly reduces oxidative stress and apoptosis and increases angiogenesis. Hematoxylin and eosin (H&E) staining and laser Doppler images further clarified the enhancement of angiogenesis after catalpol treatment. The impact of catalpol in flap was switched by using 3-methyladenine (3MA), proving the important role of autophagy in curative effect of catalpol on skin flaps. Importantly, the ability of catalpol to regulate autophagy is mediated by the activation of sirtuin 1 (SIRT1) based on its high affinity for SIRT1. Our findings revealed that catalpol improved the viability of random skin flaps by activating SIRT1-mediated autophagy pathway.

Photobiomodulation effect in tumoral necrosis factor-alpha(TNF-α) on the viability of random skin flap in rats.

The aim of this study was to investigate the effect of red laser (660 nm) photobiomodulation (PBM) with different energies on tumor necrosis factor-alpha(TNF-α) expression for random skin flap viability in rats. Twenty-four Wistar rats were divided into three groups: sham group (SG), PBM laser group with an energy dose of 0.29 J (0.29G), and PBM laser group with an energy dose of 7.30 J (7.30G). A cranially based dorsal skin flap measuring 10 × 4 cm was raised and a plastic barrier was placed between the flap and its bed. PBM was applied in 3 timepoints: in the immediate postoperative period, in the 1st and in the 2nd postoperative days; the animals were euthanized on the 7th postoperative day. The assessments included: TNF-α expression of 3 different flap areas (proximal, medial and distal), by immunohistochemistry; percentage of skin flap necrosis area, by the paper template method. The statistical analysis was performed through the Kruskal-Wallis and Mann-Whitney tests, the level of significance adopted was 5% (p < 0.05). TNF-α expression was significantly lower for 7.30G in the proximal area, reduced for SG in the medial point, and larger for 7.30G in the distal area. The percentage of flap necrosis area was significantly reduced for 7.30G. Higher energy doses are more efficacious than lower energy doses for modulating TNF-α expression. PBM with an energy dose of 7.30 J was effective in reducing the expression of TNF-α and increase skin flap viability.

Blood Perfusion of Random Skin Flaps in Humans-In Vivo Assessment by Laser Speckle Contrast Imaging.

The viability of random skin flaps (RSFs) depends on an adequate perfusion pressure to avoid necrosis. Laser speckle contrast imaging is a new method to monitor skin flap microcirculation. The authors aimed to use laser speckle contrast imaging in evaluating the correlation between the perfusion pressure and the length-to-width ratio (LTWR) of RSFs. Sixty patients submitted to flaps were included: 20 advancement, 20 rotation, and 20 transposition flaps. Laser speckle contrast imaging measurements of perfusion were obtained-after the flaps were planned, dissected, and sutured-from the base to the tip of the flaps, allowing the creation of plot charts and calculation of linear regression equations. Perfusion consistently and significantly decreased with the dissection of all flaps. A significant correlation between LTWR and perfusion was observed in undermined and sutured stages; a mathematical model was then delineated, explaining objectively the drop of perfusion along LTWR, with statistical significance, in all flaps. Laser speckle contrast imaging allows accurate, rapid, reproducible, and noncontact measurements of skin blood perfusion over RSF, ultimately leading to an optimization of skin flap planning. This study proves that variation of perfusion pressure along the flap is dependent on the LTWR in a linear decreasing function.

Apigenin enhances viability of random skin flaps by activating autophagy.

Random skin flap is widely used in plastic surgery. However, flap necrosis caused by ischemia-reperfusion injury limits its clinical applications. Apigenin, a naturally occurring flavonoid mainly derived from plants, facilitates flap survival. In this study, we explored the effects of apigenin on flap survival and the underlying mechanisms. A total of 54 mice having a dorsal random flap model were randomly divided into control, apigenin, and apigenin +3-methyladenine groups. These groups were treated with dimethyl sulfoxide solution, apigenin, and apigenin +3-methyladenine, respectively. The animals were then euthanized to assess angiogenesis, apoptosis, oxidative stress, and autophagy levels through histological and protein analyses. Apigenin promotes survival of the skin flap area and reduces tissue edema. In addition, apigenin enhanced angiogenesis, attenuated apoptosis, alleviated oxidative stress, and activated autophagy. Interestingly, 3-methyladenine reversed the effects of apigenin on flap survival, angiogenesis, apoptosis, and oxidative stress through inhibition of autophagy. The findings of this study show that apigenin promotes angiogenesis, inhibits cell apoptosis, and lowers oxidative stress by mediating autophagy, thus the improving survival rate of random skin flaps.

Positive Effect of Andrographolide Induced Autophagy on Random-Pattern Skin Flaps Survival.

Random-pattern skin flap replantation is generally used in the reconstruction of surgical tissues and covering a series of skin flap defects. However, ischemia often occurs at the flap distal parts, which lead to flap necrosis. Previous studies have shown that andrographolide (Andro) protects against ischemic cardiovascular diseases, but little is known about the effect of Andro on flap viability. Thus, our study aimed to building a model of random-pattern skin flap to understand the mechanism of Andro-induced effects on flap survival. In this study, fifty-four mice were randomly categorized into the control, Andro group, and the Andro+3-methyladenine group. The skin flap samples were obtained on postoperative day 7. Subsequently, the tissue samples were underwent a series of evaluations such as changes in the appearance of flap tissue, the intensity of blood flow, and neovascularization density of skin flap. In our study, the results revealed that Andro enhanced the viability of random skin flaps by enhancing angiogenesis, inhibiting apoptosis, and reducing oxidative stress. Furthermore, our results have also demonstrated that the administration of Andro caused an elevation in the autophagy, and these remarkable impact of Andro were reversed by 3-methyladenine (3-MA), the most common autophagy inhibitor. Together, our data proves novel evidence that Andro is a potent modulator of autophagy capable of significantly increasing random-pattern skin flap survival.

Effectiveness of Pre PRP Injection and Post Elevation Flap at Extended Random Flap Rat Skin

Background:Closure of the defect with a random skin flap is constrained by the extent of the defect area. Several studies have shown the benefits of administration of PRP (Platelet Rich Plasma) in random skin flap. The purpose of this study is to compare the effect of PRP injection given before flap elevation, after flap elevation and control on the extended random skin flap procedures in rats.Methods: This research is experimental with randomized post test only control group design (n = 27, divided into 3 treatment groups) that compare the effectiveness of PRP injection 24 hours prior to the elevation of the flap, after the elevation of the flap, and control in the extended random skin flap in rats. Random skin flap is made in the ratio 1: 5 on the rat skin. Measurement of viable area were observed on days 1, 7 and 14.Results: There were significantly increased viability of random skin flap on the group with PRP injection 24 hours prior flap elevation compared to other group of treatment. The average of viability on day first 39%±13% ;42%±34%; 62%±14%. On day 7th24%±13%; 36%±26%; 62%±12%.On day 14th16%±15%; 28%±22%; 60%±11%.Conclusion: Injection of PRP on extended random skin flap on rat 24 hours before flap elevationincrease viability of the flap compared to control group and group which receive PRP injection on extended random flap on rat skin after elevation of the flap. Viability increased due to angiogenesis stimulation after PRP injection.

Exenatide improves random-pattern skin flap survival via TFE3 mediated autophagy augment.

Random-pattern skin flaps are widely applied to rebuild and restore soft-tissue damage in reconstructive surgery; however, ischemia and subsequent ischemia-reperfusion injury lead to flap necrosis and are major complications. Exenatide, a glucagon-like peptide-1 analog, exerts therapeutic benefits for diabetic wounds, cardiac injury, and nonalcoholic fatty liver disease. Furthermore, Exenatide is a known activator of autophagy, which is a complex process of subcellular degradation that may enhance the viability of random skin flaps. In this study, we explored whether exenatide can improve skin flap survival. Our results showed that exenatide augments autophagy, increases flap viability, enhances angiogenesis, reduces oxidative stress, and alleviates pyroptosis. Coadministration of exenatide with 3-methyladenine and chloroquine, potent inhibitors of autophagy, reversed the beneficial effects, suggesting that the therapeutic benefits of exenatide for skin flaps are due largely to autophagy activation. Mechanistically, we identified that exenatide enhanced activation and nuclear translocation of TFE3, which leads to autophagy activation. Furthermore, we found that exenatide activates the AMPK-SKP2-CARM1 and AMPK-mTOR signaling pathways, which likely lead to exenatide's effects on activating TFE3. Overall, our findings suggest that exenatide may be a potent therapy to prevent flap necrosis, and we also reveal novel mechanistic insight into exenatide's effect on flap survival.

Effectiveness of Pre PRP Injection and Post Elevation Flap at Extended Random Flap Rat Skin

Closure of the defect with a random skin flap is constrained by the extent of the defect area. Several studies have shown the benefits of administration of PRP (Platelet Rich Plasma) in random skin flap. The purpose of this study is to compare the effect of PRP injection given before flap elevation, after flap elevation and control on the extended random skin flap procedures in rats. This was an experimental study with randomized posttest-only control group design (n=27, divided into 3 treatment groups) that compare the effectiveness of PRP injection 24 hours prior to the elevation of the flap, after the elevation of the flap, and control in the extended random skin flap in rats. Random skin flap is made in the ratio 1: 5 on the rat skin. Measurement of viable area were observed on days 1, 7 and 14. There were significantly increased viability of random skin flap on the group with PRP injection 24 hours prior flap elevation compared to other group of treatment. The average of viability on day first 39%±13% ;42%±34%; 62%±14%. On day 7th 24%±13%; 36%±26%; 62%±12%. On day 14th 16%±15%; 28%±22%; 60%±11%. Injection of PRP on extended random skin flap on rat 24 hours before flap elevation increase viability of the flap compared to control group and group which receive PRP injection on extended random flap on rat skin after elevation of the flap. Viability increased due to angiogenesis stimulation after PRP injection.

Exenatide Improves the Survival of Random-Pattern Skin Flap &lt;i&gt;via&lt;/i&gt; TFE3 Mediated Autophagy Augment

Background: Random skin flaps are widely applied to rebuild and restore soft-tissue damage in reconstructive surgery. Nevertheless, severe ischemia and ischemia/reperfusion injury lead to flap necrosis, a major complication after operation occurring in reconstructive surgery. Exenatide exert therapeutic role in diabetic wounds, cardiac injury, and nonalcoholic fatty liver disease. However, whether Exenatide has a protective effect against flap necrosis remains unknown, and the underlying mechanism should be explored further. Methods: One hundred and forty-four mice were stochastically divided into the Control (n=30), Exe(n=30), Exe + 3 methyladenine (3MA) (n=24), Exe + chloroquine (CQ) (n=24), Exe + Scramble control (n=18), and Exe + TFE3 shRNA groups (n = 18). Flap tissues were obtained on postoperative day 7 to evaluate tissue vitality, angiogenesis, pyroptosis, oxidative stress, and autophagy using Immunohistochemistry, Immunofluorescence staining and western blotting. Findings: We found Exenatide increased the flap vitality, enhanced angiogenesis, reduced oxidative stress and alleviated pyroptosis and activate autophagy in random skin flap. Inhibition of autophagy by 3MA and CQ reversed the above effects of Exenatide in random skin flap, suggesting that autophagy exert a major role in pro-survival effect in skin flap. In mechanistic investigation, activation and nuclear translocation of TFE3 was found to mediate Exenatide – induced autophagy. Besides, nuclear translocation of TFE3 may result from activation of AMPK-SPK2-CARM1 and AMPK-mTOR signaling axis. Interpretation: Our findings revealed that Exenatide boosted the viability, enhanced angiogenesis, reduced oxidative stress, alleviated pyroptosis via upregulation of autophagy. These indicated that Exenatide is a potent autophagy enhancer and capable for promoting the viability of random skin flap, providing a promising novel therapeutic strategy. Funding Statement: Financial supports from Public Welfare Technology Research Project of Natural Science Foundation of China (No. 81601705 to Kailiang Zhou, No.81873942 to Weiyang Gao, No. 81801930 to Jian Ding, No. 81572227 and No. 81873992 to Huazi Xu); Zhejiang Provincial Medicine and Health Technology Project (No. 2017KY472 to Kailiang Zhou); Wenzhou Science and Technology Bureau Foundation (No.2016Y0350 to Jian Ding). Declaration of Interests: The author states that there is no conflict of interest. Ethics Approval Statement: Experimental steps involving animals strictly abided by the Guide for the Care and Use of Laboratory Animals of the China National Institutes of Health, which were approved of the Animal Care and Use Committee of Wenzhou Medical University (wydw2017–0022).

FGF21 augments autophagy in random-pattern skin flaps via AMPK signaling pathways and improves tissue survival

Random-pattern skin flap is commonly used for surgical tissue reconstruction due to its ease and lack of axial vascular limitation. However, ischemic necrosis is a common complication, especially in distal parts of skin flaps. Previous studies have shown that FGF21 can promote angiogenesis and protect against ischemic cardiovascular disease, but little is known about the effect of FGF21 on flap survival. In this study, using a rat model of random skin flaps, we found that the expression of FGF21 is significantly increased after establishment skin flaps, suggesting that FGF21 may exert a pivotal effect on flap survival. We conducted experiments to elucidate the role of FGF21 in this model. Our results showed that FGF21 directly increased the survival area of skin flaps, blood flow intensity, and mean blood vessel density through enhancing angiogenesis, inhibiting apoptosis, and reducing oxidative stress. Our studies also revealed that FGF21 administration leads to an upregulation of autophagy, and the beneficial effects of FGF21 were reversed by 3-methyladenine (3MA), which is a well-known inhibitor of autophagy, suggesting that autophagy plays a central role in FGF21’s therapeutic benefit on skin flap survival. In our mechanistic investigation, we found that FGF21-induced autophagy enhancement is mediated by the dephosphorylation and nuclear translocation of TFEB; this effect was due to activation of AMPK-FoxO3a-SPK2-CARM1 and AMPK-mTOR signaling pathways. Together, our data provides novel evidence that FGF21 is a potent modulator of autophagy capable of significantly increasing random skin flap viability, and thus may serve as a promising therapy for clinical use.

Intra-arterial injection of human adipose-derived stem cells improves viability of the random component of axial skin flaps in nude mice

Skin flap necrosis is a common postoperative complication in reconstructive surgery. Recent evidence suggests that subcutaneously injected adipose-derived stem cells (ASCs) increase the viability of random skin flaps. Here, we examined whether intra-arterial human ASC administration could improve random component survival of axial skin flaps in nude mice. Human ASCs isolated from a healthy volunteer by liposuction were injected into nude mice through the right femoral artery at a low (1 × 103 cells), medium (1 × 104 cells), or high (1 × 105 cells) dose. After ASC infusion, right superficial inferior epigastric vessels were ligated to create unipedicled superficial inferior epigastric artery (SIEA) flap with random extension. Flap survival was higher in mice from all three ASC-treated groups, and particularly the medium-dose group was 30% better, than in the control group. Histological examination demonstrated a significantly higher vascular density in the axial skin flap in nude mice treated with the medium ASC dose than in control mice. PKH26-labeled ASCs were identified in skin flaps of ASC-treated mice; some endothelial cells exhibited positive staining for human HLA-A. Compared to the control group, mice in ASC-treated groups had higher vascular endothelial growth factor levels and lower tumor necrosis factor α, interferon γ, and interleukin-6 levels. Intra-arterial human ASC administration increased the survival of axial skin flaps by attenuating inflammatory reactions and enhancing neovascularization. Intra-arterial ASC administration might yield a higher rate of these cells and of engraftment in the skin flaps. This approach may have a therapeutic role in increasing flap survival.

Trehalose promotes the survival of random-pattern skin flaps by TFEB mediated autophagy enhancement

Random-pattern skin flaps are commonly used and valuable tools in reconstructive surgery, however, post-operative random skin flap necrosis remains a major and common complication. Previous studies have suggested that activating autophagy, a major pathway for degradation of intracellular waste, may improve flap survival. In this study, we investigated whether trehalose, a novel and potent autophagy activator, improves random skin flap viability. Our results demonstrated that trehalose significantly improves viability, augments blood flow, and decreases tissue edema. Furthermore, we found that trehalose leads to increased angiogenesis, decreased apoptosis, and reduced oxidative stress. Using immunohistochestry and western blot, we demonstrated that trehalose augments autophagy, and that inhibition of autophagy augmentation using 3MA significantly blunted the aforementioned benefits of trehalose therapy. Mechanistically, we showed that trehalose’s autophagy augmentation is mediated by activation and nuclear translocation of TFEB, which may be due to inhibition of Akt and activation of the AMPK-SKP2-CARM1 signaling pathway. Altogether, our results established that trehalose is a potent agent capable for significantly increasing random-pattern skin flap survival by augmenting autophagy and subsequently promoting angiogenesis, reducing oxidative stress, and inhibiting cell death.

The Effect of Topical Vitamin A and E on Ischemic Random Skin Flap Survival.

BACKGROUNDIschemia of skin flaps is an important complication in reconstructive surgery. This study evaluated the efficacy of topical vitamins A and E on improving flap survival. METHODSTwenty-four white-albino male rats were randomly divided into two groups of treatment and control. Standard rectangular, distally based dorsal random pattern skin flap was elevated. Intra-peritoneal cephazoline was administered to prevent any unexpected infection. No pharmaceutical agent was administered for the control group, but pure vaseline ointment. In treatment group, vaseline plus vitamins A and E were administrated daily after surgery for 10 days. The rats were evaluated on the 10th day after surgery for viable and necrotic portions of the flaps. RESULTSThe mean values of necrosis in the flaps were 625±189.56 and 920.00±247.31 in the treatment and control groups, respectively. Vaseline plus vitamins increased flap survival significantly.CONCLUSIONTopical vitamins A and E may be effective pharmaceutical agents to increase viability of random skin flaps in rats. They can be added to vasoactive topical agents to reach better results.

Effects of Morroniside on the Viability of Random Skin Flaps in Rats

ABSTRACTObjective: The purpose of our experiment was to determine whether morroniside can improve the survival of ischemic skin flaps in rats. Methodology: A total of 40 male Sprague-Dawley rats were randomly divided into two groups (control group and treatment group). Modified McFarlane flaps were performed (causally based, 9 cm × 3 cm). The percentage of survival of each flap was calculated. Flap blood flows were measured by Laser-Doppler flowmeter. Flap vasculature was assessed by angiography after Lead oxide-gelatin injection. Vascular endothelial growth factor (VEGF) was evaluated by immunochemistry. Superoxide Dismutase (SOD) level and malondiadehyde (MDA) content were determined using assay kits. Results: At the seventh postoperative day, the morroniside-treated rats showed a higher percentage of flap survival than the control rats. Flap perfusion and the level of vascular endothelial growth factor were significantly elevated in the morroniside-treated group. In the treatment group, the distal section of the flap was nearly saturated with contrast agent, while in the control group, the contrast agent perfused only half of the flap. In the treatment group, morroniside administration significantly increased SOD level and reduced MDA content. Conclusion: Morroniside can enhance ischemic flap survival.

Effects of Clopidogrel and Low-Molecular-Weight Heparin on Viability of Random Skin Flaps in Rats

Background The viability of skin flaps is critical and greatly affects patient's quality of life. Effects of anticoagulant use on focal skin flap necrosis were explored, administering clopidogrel or low-molecular-weight heparin (LMWH) singly and in combination. Methods Adult male rats ( N = 40) were randomly assigned to one of four equally divided groups, raising a random dorsal flap (10 × 4 cm) on each animal and delivering either no drug (control group) or daily applications of LMWH (4 mg/kg), clopidogrel (20 mg/kg), or both agents (LMWH–Clop) for a 7-day period. Thereafter, area and the percentage of flap necrosis (NP) were individually determined. Results Average NP values were as follows: controls, 51.61%; LMWH, 49.50%; clopidogrel, 27.70%; and LMWH–Clop, 29.71%. Conclusion Clopidogrel significantly enhanced the viability of random skin flap in rats, whereas single-agent LMWH or its combined usage conferred no significant benefits in this setting.

Inhibitory effects of low-level laser therapy on skin-flap survival in a rat model

Although several studies have demonstrated the effects of low-level laser therapy (LLLT) on skin flap viability, the role of higher doses has been poorly investigated. To investigate the inhibitory effect of the LLLT (λ=670 nm) on the viability of random skin flaps in a rat model using an irradiation energy of 2.79 J at each point. Sixteen Wistar rats were randomly assigned into two groups: sham laser irradiation (n=8); and active laser irradiation (n=8). Animals in the active laser irradiation group were irradiated with a 670 nm diode laser with an energy of 2.79 J/point, a power output 30 mW, a beam area of 0.028 cm(2), an energy density of 100 J/cm(2), an irradiance of 1.07 W/cm(2) for 93 s/point. Irradiation was performed in 12 points in the cranial skin flap portion. The total energy irradiated on the tissue was 33.48 J. The necrotic area was evaluated on postoperative day 7. The sham laser irradiation group presented a mean (± SD) necrotic area of 47.96±3.81%, whereas the active laser irradiation group presented 62.24±7.28%. There was a significant difference in skin-flap necrosis areas between groups (P=0.0002). LLLT (λ=670 nm) increased the necrotic area of random skin flaps in rats when irradiated with an energy of 2.79 J (100 J/cm(2)).