Flap Survival In Rats Research Articles

Dietary nitrate maintains homeostasis of oxidative stress and gut microbiota to promote flap survival in type 2 diabetes mellitus rats

BackgroundRandom-pattern skin flaps are commonly used to repair skin tissue defects in surgical tissue reconstruction. However, flap necrosis in the distal area due to ischemia injury is still challenging for its applications in plastic surgery. The complications of diabetes will further increase the risk of infection and necrosis.MethodsThis study induced type 2 diabetes mellitus (T2DM) rats with a high-fat diet and STZ. The survival rate of the skin flap was observed by adding inorganic sodium nitrate to drinking water. Histology and immunohistochemistry were used to detect the damage to the skin flap. The nitrate content was measured by total nitric oxide and nitrate/nitrite parameter assay. Dihydroethidium and malondialdehyde (MDA) assays were used to value oxidative stress. Rat colon feces were collected for 16s rRNA gene sequence.ResultsOur studies showed that nitrate administration leads to anti-obesity and anti-diabetic effects. Nitrate directly increased the survival area of skin flaps in diabetic rats and mean blood vessel density by enhancing angiogenesis, inhibiting apoptosis, and reducing oxidative stress. The 16s rRNA sequence revealed that nitrate may regulate the homeostasis of the gut microbiota and re-store energy metabolism.ConclusionDietary nitrate has been shown to maintain the homeostasis of oxidative stress and gut microbiota to promote flap survival in rats with T2DM.

Enhancing Skin Flap Survival with Preoperative Carbon Dioxide Fractional Laser Treatment: A Novel Approach in Reconstructive Surgery

Background: Skin flap necrosis remains a significant challenge in reconstructive surgery, predominantly due to insufficient blood supply. Traditional methods like the surgical delay procedure, while effective, are invasive and associated with considerable patient discomfort and health care costs. This study explores the efficacy of Carbon Dioxide Fractional Laser (CDFL) treatment as a novel, less invasive alternative to enhance skin flap survival. Methods: Twenty-nine adult male Sprague-Dawley rats were divided into 2 groups: a CDFL treatment group (n=14) and a control group (n=15). The CDFL group received laser pretreatment 1 week before flap surgery, whereas the control group underwent flap surgery without pretreatment. Flap survival was assessed 7 days postsurgery using indocyanine green fluorescence angiography. In addition, histological analysis was conducted to evaluate tissue integrity, capillary density, and VEGF expression. Results: The CDFL-treated flaps showed significantly increased survival areas compared with controls (P<0.01). Histological evaluation revealed enhanced capillary dilation and increased VEGF expression in the CDFL group (P<0.05). Although capillary density was higher in the CDFL group, it did not reach statistical significance (P=0.052). Conclusion: CDFL pretreatment significantly improves skin flap survival in rats, suggesting potential as a minimally invasive alternative to traditional surgical delay techniques. This approach could offer substantial benefits in reconstructive surgery, reducing patient morbidity and associated costs. Further studies are warranted to confirm these findings in clinical settings.

Spermidine Exerts Protective Effects in Random-Pattern Skin Flap Survival in Rats: Possible Involvement of Inflammatory Cytokines, Nitric Oxide, and VEGF.

Distal necrosis and inflammation are two of the most common health consequences of random-pattern skin flaps survival (SFS). Anti-inflammatory effects of spermidine have been identified in various studies. On the other hand, considering the involvement of the nitric oxide molecule in the spermidine mode of action and also its role in skin tissue function, we analyzed the possible effects of spermidine on the SFS and also, potential involvement of nitrergic pathway and inflammatory cytokine in these phenomena. Each rat was pretreated with either a vehicle (control) or various doses of spermidine (0.5, 1, 3, 5, 10 and 30 mg/kg) and then was executed a random-pattern skin flap paradigm. Also, spermidine at the dose of 5 mg/kg was selected and one group rats received spermidine 20 min prior to surgery and one additional dose 1 day after operation. Then, 7 days after operations, interleukin (IL)-6, tumor necrosis factor (TNF)-α, interferon-gamma (IFN-γ), and nitrite levels were inquired in the tissue samples by ELIZA kit. Vascular endothelial growth factor expression was assessed by DAPI staining and fluorescent microscopes. The concentrations of three polyamines, including spermidine, spermine, and cadaverine, were analyzed using HPLC. Pretreatment with spermidine 5 mg/kg improved SFS considerably in microscopic skin H&E staining analysis and decreased the percentage of necrotic area. Moreover, spermidine exerted promising anti-inflammatory effects via the modulation of nitric oxide and reducing inflammatory cytokines. Spermidine could improve skin flaps survival, probably through the nitrergic system and inflammation pathways. This preclinical study provides level III evidence for the potential therapeutic effects of spermidine on SFS in rats, based on the analysis of animal models. Further studies are needed to confirm these findings in clinical settings. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Effects of systemically administered tramadol hydrochloride on random pattern skin flap survival in rats

Aim: Tramadol is a weak centrally acting opioid analgesic with µ-opioid receptor agonist effects. It has been explored for its analgesic efficacy through various in-vitro and in-vivo studies. The skin, as the body’s largest organ and the protector barrier, is vulnerable to injuries and wounds that can cause significant challenges due to pain, economic burdens and psychological implications. Successful healing of wound involves complex processes and it is influenced by factors such as angiogenesis and nitric oxide levels. This study investigates the effects of tramadol on wound healing in experimental ischemic wound models in rats. Material and Methods: Two 6 mm ischemic wound models were created on the backs of 30 male Wistar Albino rats, with wound areas cut along the long edges and a sterile silicone material placed between the panniculus carnosus fascia and paraspinosus muscle. Rats were randomized into Tramadol, Control, and Sham groups. The wounds were imaged using a "SONY ILCE-7" camera on days 0, 3, 6, 10, and 14. Wound areas and healing percentages were calculated from the images and recorded for statistical purposes. After 14 days, the animals were sacrificed under general anesthesia for histopathological examination of tissue samples. CD31 and VEGF antibodies were used to evaluate the density and morphology of vascular structures. Results: Tramadol administration accelerated the healing of wound surface area. Significant differences were found between groups in terms of inflammation, and data recorded in CD34, CD31, and VEGF-stained preparations. Conclusion: The study found that tramadol positively contributes to wound healing in the acute phase of ischemic wounds by affecting various processes.

Tetrahydropalmatine promotes random skin flap survival in rats via the PI3K/AKT signaling pathway

Ethnopharmacological relevanceFlap necrosis is the most common complication after flap transplantation, but its prevention remains challenging. Tetrahydropalmatine (THP) is the main bioactive component of the traditional Chinese medicine Corydalis yanhusuo, with effects that include the activation of blood circulation, the promotion of qi, and pain relief. Although THP is widely used to treat various pain conditions, its impact on flap survival is unknown. Aim of the studyTo explore the effect and mechanism of THP on skin flap survival. Materials and methodsIn this study, we established a modified McFarlane flap model, and the flap survival rate was calculated after 7 days of THP treatment. Angiogenesis and blood perfusion were evaluated using lead oxide/gelatin angiography and laser Doppler, respectively. Flap tissue obtained from zone II was evaluated histopathologically, by hematoxylin and eosin staining, and in assays for malondialdehyde content and superoxide dismutase activity. Immunofluorescence was performed to detect interleukin (IL)-6, tumor necrosis factor (TNF)-α, hypoxia-inducible factor (HIF)-1α, Bcl-2, Bax, caspase-3, caspase-9, SQSTM1/P62, Beclin-1, and LC3 expression, and Western blot to assess PI3K/AKT signaling pathway activation and Vascular endothelial growth factor (VEGF) expression. The role played by the autophagy pathway in flap necrosis was examined using rapamycin, a specific inhibitor of mTOR. ResultsExperimentally, THP improved the survival rate of skin flaps, promoted angiogenesis, and improved blood perfusion. THP administration reduced the inflammatory response, oxidative stress, and apoptosis in addition to inhibiting autophagy via the PI3K/AKT/mTOR pathway. Rapamycin partially reversed these effects. ConclusionTHP promotes skin flap survival via the PI3K/AKT signaling pathway.

Chronic Cinacalcet improves skin flap survival in rats: the suggested role of the nitric oxide pathway.

Cinacalcet is a calcimimetic medicine that has been used to treat secondary hyperparathyroidism and parathyroid cancer. Various studies have proposed the positive role of calcium and its receptor in skin wound healing. Furthermore, Cinacalcet interacts with other skin repair-related mechanisms, including inflammation and nitric oxide pathways. The present study evaluated the effect of Cinacalcet on the random-pattern skin flap survival. Eighty-four Wistar male rats were used. Multiple doses of Cinacalcet (30, 3, 1, 0.3, and 0.05 mg/kg) were used in 3 different routes of administration before the surgery. Histopathological evaluations, quantitative assessment of IL-6, TNF-α, and nitric oxide (NO), and the expression of calcium-sensing receptor (CaSR) and E-cadherin were evaluated in the skin tissue. To assess the role of NO, a NO synthase inhibitor, N-nitro-L-arginine methyl ester hydrochloride (L-NAME), was used, and histopathological effects were investigated. Cinacalcet pretreatment at the IP chronic 1 mg/kg dose significantly increased the skin flap survival rate and enhanced the NO tissue level compared to the control. However, the administration of L-NAME abolished its protective effects. IP Chronic 1 mg/kg of Cinacalcet could also decline the levels of IL-6 and TNF-α and also increase the expression of CaSR and E-cadherin in the flap tissue compared with the control group. Chronic Cinacalcet at 1 mg/kg could improve skin flap survival, probably mediated by the CaSR, NO, and inflammation-related pathways.

Effects of Intramuscular Epinephrine Injection and Systemic Sildenafil Citrate on Rat Transverse Rectus Abdominis Musculocutaneous Flap Survival

Background and Objectives Flaps are commonly employed for reconstruction, and many studies have sought to improve flap survival. In this study, we determined whether sildenafil and epinephrine synergistically improve the survival rate of transverse rectus abdominis musculocutaneous (TRAM) flaps.Materials and Method Twenty-four Sprague-Dawley rats were divided into four groups of six rats each: a control group, an epinephrine group, a sildenafil group, and an epinephrineplus- sildenafil group. TRAM flaps were elevated on the upper abdomen.Results The average flap survival area and number of blood vessels differed significantly between the control and experimental groups; however, the various experimental groups did not differ significantly. The level of vascular epithelial growth factor was higher in the experimental groups than in the control group.Conclusion Both epinephrine and sildenafil citrate significantly improve TRAM flap survival in rats. However, whether effects are better when the drugs are combined rather than when used alone remains unclear. Further research is required.

Nesfatin-1 regulates the HMGB1-TLR4-NF-κB signaling pathway to inhibit inflammation and its effects on the random skin flap survival in rats

ObjectiveRandom skin flaps are often placed by plastic surgeons to treat limb deformities and dysfunction. Nesfatin-1 (NES) is a peptide that exerts angiogenic, anti-inflammatory, and anti-oxidant effects. We assessed the impact of NES on flap survival and the underlying mechanism. MethodsWe modified the McFarlane random skin flap rat model. Thirty-six male Sprague-Dawley rats were randomly divided into a control group (corn oil solution with DMSO), low-dose group (NES-L at 10 µg/kg/day), and high-dose group (NES-H at 20 µg/kg/day). On day 7 after surgery, average flap survival areas were calculated. Laser Doppler blood flow monitoring and lead oxide/gelatin angiography were used to evaluate blood perfusion and neovascularization, respectively. Flap histopathological status was evaluated by hematoxylin and eosin (H&E) staining. The levels of superoxide dismutase (SOD) and malondialdehyde (MDA) were determined. Immunohistochemical techniques were used to evaluate the expression of angiogenetic and inflammatory factors. ResultsIn the experimental groups, the mean skin flap survival areas and blood perfusion increased considerably. The SOD activities in the experimental groups increased and the MDA contents decreased. Immunohistochemically, VEGF expression was upregulated in the experimental groups and the expression levels of inflammatory factors decreased markedly. ConclusionNES inhibited ischemic skin flap necrosis, promoted angiogenesis, and reduced ischemia-reperfusion injury and inflammation. Inhibition of the inflammatory HMGB1-TLR4-NF-κB signal pathway, which reduced flap inflammation and oxidative stress, may explain the enhanced flap survival.

Effects of pharmacological delay with roxadustat on multi-territory perforator flap survival in rats.

Roxadustat (FG-4592) is a specific hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitor. We investigated the effects of FG-4592 pretreatment on survival and second choke vessels of multi-territory perforator flaps in rats. In total, 72 rats were divided into two groups (n = 36 each): the experimental (FG-4592) group and the control group. FG-4592 was administered orally as a single dose of 60 mg/kg every other day; the first drug solution was administered to the animals 7 days before the surgical procedure. On postoperative day 7, the surviving flap area was calculated. At 12 h post-surgery, in the second choke zone in the flaps, macrovascular hinges were compared by angiography and imaging, and microvascular changes were assessed by histology. Laser Doppler imaging was used to evaluate flap perfusion at the second choke zone at 12 h and 7 days after surgery. At 7 days after surgery, the flap survival area and perfusion were significantly greater in rats given FG-4592 compared with controls. At 12 h after surgery, the diameter of macrovascular and microvascular vessels, nitric oxide content, perfusion, and the protein levels of HIF-1α and inducible nitric oxide synthase were also significantly greater in FG-4592-treated rats than controls. In conclusion, pretreatment with roxadustat may improve initial flap survival and dilate the second choke zone vessels in a multi-territory perforator flap.

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.

Roxadustat promotes hypoxia-inducible factor-1α/vascular endothelial growth factor signalling to enhance random skin flap survival in rats.

Random skin flaps have limited clinical application as a broad surgical reconstruction treatment because of distal necrosis. The prolyl hydroxylase domain-containing protein inhibitor roxadustat (RXD) enhances angiogenesis and reduces oxidative stress and inflammation. This study explored the function of RXD in the survival of random skin flaps. Thirty-six male Sprague-Dawley rats were randomly divided into low-dose RXD group (L-RXD group, 10 mg/kg/2 day), high-dose RXD group (H-RXD group, 25 mg/kg/2 day), and control group (1 mL of solvent, 1:9 DMSO:corn oil). The proportion of surviving flaps was determined on day 7 after surgery. Angiogenesis was assessed by lead oxide/gelatin angiography, and microcirculation blood perfusion was evaluated by laser Doppler flow imaging. Specimens in zone II were obtained, and the contents of superoxide dismutase (SOD) and malondialdehyde (MDA) were measured as indicators of oxidative stress. Histopathological status was evaluated with haematoxylin and eosin staining. The levels of hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF), and the inflammatory factors interleukin (IL)-1β, IL-6, and tumour necrosis factor-α (TNF-α) were detected by immunohistochemistry. RXD promoted flap survival and microcirculatory blood perfusion. Angiogenesis was detected distinctly in the experimental group. SOD activity increased and the MDA level decreased in the experimental group. Immunohistochemistry indicated that the expression levels of HIF-1α and VEGF were increased while the levels of IL-6, IL-1β, and TNF-α were decreased after RXD injection. RXD promoted random flap survival by reinforcing vascular hyperplasia and decreasing inflammation and ischaemia-reperfusion injury.

The effect of Ranolazine on random pattern skin flap survival in rats

Objective: Flap surgery is widely used in the field of plastic surgery for defect reconstruction. The most important problem of this surgery is ischemic necrosis which may occur in the distal of the flap. For this reason, studies have been conducted to develop many treatment methods to solve this problem. Our study aimed to investigate the effects of different doses of ranolazine, a selective late sodium current blocker, on the viability of skin flaps prepared from the back of the rat. Material and Methods: A total of 32 rats, including 8 rats in each group, were included in the study. A random patterned caudal base 3x9 cm width : length modified McFarlane skin flap was elevated from the backs of all rats and adapted back to its place For 7 days postoperatively, 1 cc of saline was added to the control group (Group A), and 45 mg/kg, 90 mg/kg, and 180 mg/kg of ranolazine were added to the study groups (Group B, C, D), respectively, and administered daily with gastric lavage On the 7th postoperative day, photographs were taken to evaluate the viability of the flaps and scintigraphic evaluations were made. After the rats were sacrificed, the flaps were separated from their bases and evaluated histopathologically. Results: As a result of the evaluations, the viable flap area was calculated as 12.7548 cm2 for Group A, 14.9533 cm2, 16.494 cm2 and 16.7599 cm2 for Groups B, C and D, respectively, and a statistically significant difference was found between the groups (P = 0.00 <0.05 ). The viable flap area percentages were calculated as 57.486% for Group A, 68.908% for Group B, 70.174% for Group C and 74.603% for Group D, and a statistically significant difference was found between the groups (P = 0.00 <0.05). As a result of scintigraphic evaluation, the viable flap area was found to be 61.57% for Group A, 71.04% for Group B, 70.21% for Group C and 73.85% for Group D, and a statistically significant difference was found between the groups (P = 0.03 <0.05). Histopathological evaluation revealed a decrease in the flaps' inflammation, edema and necrosis scores with the increasing drug dose. Conclusion: As a result, although flap viability increased with increasing doses in the group given ranolazine, more detailed studies are needed before it can be used clinically.

Impact of Diameter of Perforator in Pedicle and Different Managements of Intermediate Non-Pedicle Perforator on Flap Survival in Rats

Backgrounds The quantified relationship between perforator diameter and flap length can be supported, and the impact of different strategies of managements of a non-pedicled perforator with two major subfascial divisions on flap survival has never been explored. Materials and methods This study was divided into two parts. In Part I, 48 Sprague-Dawley rats underwent flap harvesting based on six perforators with a diameter gradient. Then, the flap length and perforator diameter were measured for establishment of an equation. In Part II, 32 rats underwent harvest of a transverse flap based on the right superficial epigastric perforator. In 16 rats the right intermediate iliolumbar perforator was severed in a distal-to-division approach, whereas, in the other 16 rats, it was severed with in a proximal-to-division approach. Necrosis rates and blood perfusion were also compared. Results The equation y = 13.02 × x + 2.29 could be established between the perforator diameter in the pedicle (x) and the flap length (y) that could be supported with R2=0.8963 and P < 0.001.The transverse flap with a distal-to-division management of the intermediate iliolumbar perforasome was weaker in perfusion and had a necrosis rate of 49±4%, whereas the flap with a proximal-to division management had a significantly stronger perfusion and a lower necrosis rate of 21±2% (P<0.001). Conclusions The safe flap length that can be estimated based on a perforator with a known diameter can be calculated using y=13.02× x +2.29. A short segment of the stem of an intermediate perforator with two major subfascial branches should be preserved to augment flap survival.

Post-treatment with metformin improves random skin flap survival through promoting angiogenesis in rats.

Skin flap necrosis has been remained as an unsolved problem in plastic and reconstructive surgeries. Here, we explored the effects of metformin post-treatment on random skin flap survival in rats. An 8.00 × 2.00 cm dorsal skin flap was created in 24 rats and they were then divided into three groups (n = 8) including Control, metformin (Met) 50.00 mg kg-1 and Met 100 mg kg-1. All animals were administrated orally until seven days after flap surgery. Flap survival, the number of blood vessels and mast cells in the flap tissues were analyzed. Vascular endothelial growth factor (VEGF) expression levels in flap tissues was also determined using immunohistochemical methods. The percentage of survival area in Met 50.00 mg kg-1 and Met 100 mg kg-1 groups were significantly higher compared to control. The blood vessel density and the VEGF positive cells in the viable areas of flaps showed a significant increase in Met 50.00 mg kg-1 group compared to control group. The results of this study suggested that treatment with metformin, especially with low dose following skin flap surgery was effective in improving the flap survival and increasing the neovascularization in the flaps tissues of rats.

The Effect of Presurgical and Postsurgical Topical Tacrolimus on Pedicled Flap Survival in Rats: A Pilot Study.

Our previous rodent studies demonstrated significantly decreased full-thickness necrosis in pedicled dorsal skin flaps with topical tacrolimus as compared with petroleum jelly. Histologically, we found that topical tacrolimus was correlated with increased vascular growth in areas more susceptible to ischemic damage. The purpose of this study was to investigate the potential benefits of pretreatment with tacrolimus. By applying tacrolimus in advance of raising the dorsal skin flaps, we hoped to increase vascularity and thus increase the overall viability of the flaps. Twenty Sprague-Dawley rats were initially randomized to 4 groups based on timing of tacrolimus treatment (presurgical/postsurgical treatment): control/control (C/C), control/tacrolimus (C/T), tacrolimus/control (T/C), and tacrolimus/tacrolimus (T/T). Treatments consisted of 0.2 g of the control (topical petroleum jelly) and 0.1% topical tacrolimus to the rat dorsum twice per day. After 7 days of presurgical treatment, a cranially based dorsal skin flap measuring 3 × 10 cm was created. Two rats perished during surgery and were excluded for further analysis. Each rat was treated for a further 7 days and sacrificed. Two blinded reviewers marked the total skin flap area as well as areas of viable tissue, reversible ischemia, and full-thickness necrosis. Percentage areas were calculated using Fiji/ImageJ, and statistical analysis was performed in R. The average viable areas for C/C, C/T, T/C, and T/T were 31.4%, 31.9%, 35.6%, and 22.6%, respectively. The average reversible ischemic area for C/C, C/T, T/C, and T/T was 53.1%, 54.0%, 54.1%, and 71.5%, respectively. The average necrotic area for C/C, C/T, T/C, and T/T was 15.4%, 14.0%, 10.2%, and 5.9%, respectively. For areas of reversible ischemia, T/T arm had higher areas compared with C/T (P = 0.004) and T/C (P = 0.044). There was no significance between treatment arms for areas of viable and necrotic tissue. We observed higher areas of reversible ischemia for continuous tacrolimus treatment compared with only pre-tacrolimus application or post-tacrolimus application. This suggests that tacrolimus application before and after surgical insult may be associated with improved ischemic survival of the skin. Although we did not observe decreased areas of necrosis for tacrolimus treatment compared with control, this was likely due to the limited number of rats available in each arm to reach significance. Further study is needed to fully elucidate the encouraging trends that were observed.

Effects of Distal Arterial Supercharging and Distal Venous Superdrainage on the Survival of Multiterritory Perforator Flaps in Rats

Background Which one of the two measures, distal arterial supercharging (DAS) and distal venous superdrainage (DVS), is better to enhance flap survival? No consistent conclusions have been reached. Methods All flaps were pedicled on the deep circumflex iliac vessels. Seventy-two healthy male rats were distributed to four groups randomly: DAVS group (distal arteriovenous supercharging group), the thoracodorsal (TD) artery and TD vein were preserved; DAS group (distal arterial supercharging group), the TD vein was ligated; DVS group (distal venous superdrainage group), the TD artery was ligated; control group, the TD artery and TD vein were ligated. Flap survival rate was evaluated on postoperative day 7. Flap angiography was performed to assess vascular changes of the flap. Microvascular density (MVD) was evaluated by hematoxylin and eosin staining, and CD34-positive microvessel density was measured by immunohistochemistry. Vascular endothelial growth factor (VEGF) level was measured by western blot. The levels of superoxide dismutase (SOD) and malondialdehyde (MDA) were evaluated using specialized commercial kits. Results The mean flap survival rate was increased significantly in DAVS and DAS groups than in DVS and control groups. DAVS and DAS groups had higher flap vascularization, MVD, CD34-positive microvessel density, VEGF expression and SOD level compared to DVS and control groups. DAVS and DAS groups also had lower MDA level relative to DVS and control groups. Conclusion DAS is more conducive to improving the survival rate of the multiterritory perforator flap compared to DVS, mainly by enhancing angiogenesis and preventing ischemia-reperfusion (I/R) injury.

Involvement of Cannabinoid Type 2 Receptors in the Favorable Effects of Sumatriptan on the Random-Pattern Skin Flap Survival in Rats: A Novel Potential Target

Introduction: Recent investigations have indicated the potential therapeutic role of cannabinoid type 2 (CB2) receptors in various inflammatory-related disorders. However, the role of these receptors has not been studied in skin flap models to date. In this study, we aimed to evaluate the possible involvement of CB2 receptors in the anti-inflammatory effects of sumatriptan, improving the random-pattern skin flap survival in rats. Methods: In a controlled experimental study, 36 male Wistar rats were randomly divided into 6 study groups (n = 6 per group). Two doses of sumatriptan (0.1 and 0.3 mg/kg) were administered intraperitoneally 30 min before harvesting the flap tissue. In a separate group, SR144528 (a selective CB2 receptor inverse agonist) was injected before the most effective dose of sumatriptan to determine the possible involvement of CB2 receptors in its action. Histopathological examinations, the expression level of CB2 receptors (Western blot analysis), and IL-1β and TNF-α concentrations (ELISA) were explored in the skin flap sampled tissues. Results: Sumatriptan 0.3 mg/kg remarkably enhanced the skin flap survival in all macroscopic and microscopic investigations compared to the control group (p < 0.001). IL-1β and TNF-α levels were significantly attenuated (p < 0.001), and the expression of CB2 receptors in skin cells was amplified in rats treated with sumatriptan 0.3 mg/kg (p < 0.05) compared to the control group. However, the administration of SR144528 (2 mg/kg) nullified all the protective effects of sumatriptan 0.3 mg/kg. Conclusion: We discovered that CB2 receptors play a crucial role in the favorable effects of sumatriptan on skin flap survival as a novel mechanism of action. So, targeting these receptors seems to be a dependable method in skin flap surgeries to ensure its survival and prevent tissue necrosis. Further experimental and clinical investigations are needed to ensure the safe clinical application of this method.

The Effect of Pre- and Postsurgical Topical Tacrolimus on Pedicled Flap Survival in Rats: A Pilot Study

The Effect of Pre- and Postsurgical Topical Tacrolimus on Pedicled Flap Survival in Rats: A Pilot Study

The effect of different modes of microneedling technique on random flap survival in rats

The investigation and practice of physical therapy in flap surgery are still scare. The purpose of this study is to evaluate the impact of different microneedling interventions on survival of random pattern flaps in rats, attempting to determine the optimal microneedling protocols for improvement of flap survival. Eighty male Sprague-Dawley rats were randomly divided into four groups, with 20 in each group (group A, B, C, and D). A 3 cm×9 cm rectangular random flap as the McFarlane flap was adopted in each group. In groups A and B, microneedling treatment was performed before and after surgery, respectively. While animals in group C were received both pre- and postoperative microneedling treatment. Group D was used as a control group, which was only exposed to surgery. Flap survival, flap blood flow, number of capillary formations, the expressions of CD31, CD34, HIF-1α, and vascular endothelial growth factor (VEGF) were detected in each group and compared. On the 7th day postoperatively, significant improvements with microneedling treatment were found in flap survival rate (p = 0.007), blood flow (p = 0.024), the expression levels of CD34 (p = 0.005), and the VEGF (p<0.01). Furthermore, the VEGF expression level was significantly higher in group B when compared with the other three groups (all p<0.01). However, there was no significant difference in the number of new blood vessels and other immunohistochemical indicators among the four groups (all p>0.05). Microneedling treatment especially postoperative intervention can significantly improve the survival of random flaps in rats.

Effects of Apigenin Treatment on Random Skin Flap Survival in Rats.

Random skin flaps are often used in plastic surgery, but the complications of marginal flap ischemia and necrosis often limit their wider clinical application. Apigenin (Api) is a flavonoid found in various fruits and vegetables. Api has been shown to promote angiogenesis, as well as reduce oxidative stress, membrane damage, and inflammation. In this study, we assessed the effects of Api treatment on random skin flap survival. Dorsal McFarlane skin flaps were transplanted into rats, which were randomly divided into three groups: control (normal saline), low-dose Api (20 mg/kg), and high-dose Api (50 mg/kg). Seven days after the surgery, the activity of superoxide dismutase (SOD) and the level of malondialdehyde (MDA) were measured. Histological analyses were performed to determine flap survival and tissue edema. H&E staining was performed to assess the histopathological changes in skin flaps, and the levels of microvascular density (MVD) were determined. Laser doppler flowmetry was used to assess microcirculation blood flow. Flap angiography was performed by injection of lead oxide/gelatin. The expression levels of vascular endothelial growth factor (VEGF), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interlukin-1β (IL-lβ) were evaluated by immunohistochemistry. Rats in the high-dose Api group exhibited higher average flap survival area, microcirculatory flow, increased SOD activity, and higher VEGF expression levels compared with the other two groups. Furthermore, the levels of MDA and pro-inflammatory cytokines were significantly decreased in rats treated with high-dose Api. Our findings suggest the potential usefulness of Api in preventing skin flap tissue necrosis.