Flaps In Rats Research Articles

Methacrylated hyaluronic acid/laponite photosensitive, sustained-release hydrogel loaded with bilobalide for enhancing random flap survival through mitigation of endoplasmic reticulum stress

Random flaps are extensively utilized in plastic surgery due to their flexibility compared to traditional axial vascular system arrangements and their resemblance to injured skin in color, thickness, and texture. Despite these advantages, they are susceptible to ischemia-reperfusion injuries and subsequent necrosis post-transplantation. Bilobalide (BB), a sesquiterpene compound derived from Ginkgo biloba, exhibits notable antioxidant and anti-inflammatory properties and is commonly used to treat ischemiareperfusion injuries. However, its short half-life restricts its sustained efficacy in random flaps. In this study, we synthesized a multi-crosslinked, photosensitive methacryloyl hyaluronic acid(HAMA)/laponite(Lap)/bilobalide (BB) hydrogel. This dualcrosslinked hydrogel demonstrates superior mechanical properties and biocompatibility while providing a stable release of bilobalide. In vitro experiments showed that it significantly reduces edema, promotes angiogenesis, and enhances the survival of random flaps. Further network pharmacology analysis and recovery experiments suggested that the hydrogel's beneficial effects are mediated by the regulation of endoplasmic reticulum stress and specifically identified the regulation of the PERK/TXNIP/NLRP3 signaling pathway as crucial to its anti-inflammatory effects. Therefore, this HAMA/Lap/BB hydrogel promotes the survival of random flaps in rats by alleviating endoplasmic reticulum stress, providing a novel intervention strategy for the treatment of random flaps injuries.

The Regulatory Effect of Remifentanil on JNK Signaling during Remission of Flap Ischemia-Reperfusion Injury.

The impact of remifentanil on hypogastric flap function following ischemia-reperfusion (I/R) injury remains largely unknown, limiting its potential clinical application in flap surgery. This study investigated the therapeutic effects of remifentanil on hypogastric flap I/R injury. Aortic endothelial cells were extracted from the hypogastric flap I/R injury models established in-house using Sprague-Dawley rats, and were treated under hypoxic conditions. The cells were treated with 0.1, 1, 10 and 100 ng/mL remifentanil and 10 ng/mL anisomycin (the activator of c-Jun N-terminal kinase [JNK]). Histopathological changes and tumor necrosis factor alpha (TNF-α) content of the flaps were observed after hematoxylin-eosin staining and immunohistochemistry. Immunofluorescence, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining and flow cytometry were employed for apoptosis evaluation. Western blotting, quantitative real-time polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA) were utilized to assess the protein and gene expression levels of TNF receptor 1 (TNFR1), JNK1, phosphorylated (p)-JNK1, malondialdehyde (MDA), superoxide dismutase (SOD), nitric oxide (NO) and TNF-α in the flaps and cells. The endothelial necrosis and cell apoptosis of rat flaps induced by I/R injury were ameliorated by remifentanil, and declining aortic endothelial cell viability and augmented apoptosis induced by hypoxia were reversed by remifentanil (10, 100 ng/mL) (p < 0.05). Remifentanil reversed the increased expressions of TNFR1, JNK1, p-JNK1, MDA and TNF-α induced by I/R injury or hypoxia in the flaps and cells (p < 0.05), and counteracted the decreased levels of NO and SOD induced by I/R injury in the flaps (p < 0.05). Anisomycin reversed the effects of remifentanil on suppressing TNFR1, JNK1 and p-JNK1 levels and apoptosis in the cells (p < 0.05). Remifentanil ameliorates cell apoptosis and vascular endothelial necrosis induced by I/R injury in the hypogastric flap, likely by downregulating the TNF-α/TNFR1 pathway and JNK1 signaling. These findings suggest that remifentanil may be a promising therapeutic agent for improving hypogastric flap survival in clinical settings.

Angiosome-Guided Perfusion Decellularization of Fasciocutaneous Flaps.

Tissue engineering based on whole-organ perfusion decellularization has successfully generated small-animal organs, including the heart and limbs. Herein, we aimed to use angiosome-guided perfusion decellularization to develop an acellular fasciocutaneous flap matrix with an intact vascular network. Abdominal flaps of rats were harvested, and the vascular pedicle (iliac artery and vein) was dissected and injected with methylene blue to identify the angiosome region and determine the flap dimension for harvesting. To decellularize flaps, the iliac artery was perfused sequentially with 1% sodium dodecyl sulfate (SDS), deionized water, and 1% Triton-X100. Gross morphology, histology, and DNA quantity of flaps were then obtained. Flaps were also subjected to glycosaminoglycan (GAG) and hydroxyproline content assays and computed tomography angiography. Histological assessment indicated that cellular content was completely removed in all flap layers following a 10-hour perfusion in SDS. DNA quantification confirmed 81% DNA removal. Based on biochemical assays, decellularized flaps had hydroxyproline content comparable with that of native flaps, although significantly fewer GAGs (p = 0.0019). Histology and computed tomography angiography illustrated the integrity and perfusability of the vascular system. The proposed angiosome-guided perfusion decellularization protocol could effectively remove cellular content from rat fasciocutaneous flaps and preserve the integrity of innate vascular networks.

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.

Bone Marrow Mesenchymal Stem Cells-derived Exosomes Promote Survival of Random Flaps in Rats through Nrf2-mediated Antioxidative Stress.

Random flaps are the most used defect repair method for head and neck tumors and trauma plastic surgery. The distal part of the flap often undergoes oxidative stress (OS), ultimately leading to flap necrosis. Stem cells' exosomes exhibit potential effects related to anti-inflammatory, regenerative, and antioxidant properties. Nuclear factor erythroid-2-related factor 2 (Nrf2) is an important factor in regulating oxidative balance. Exosomes have been reported to monitor its transcription to alleviate OS. This study examined the impacts and underlying mechanisms of antioxidant actions of exosomes derived from bone marrow mesenchymal stem cells (BMSCs-Exo) on random flaps. BMSCs-Exo were injected into the tail veins of rats on days 0, 1, and 2 after surgery of random flaps. The rats were euthanized on day 3 to calculate the survival rate. Immunohistochemical staining, western blotting, dihydroethidium probe, superoxide dismutase, and malondialdehyde assay kits were used to detect the OS level. Human umbilical vein endothelial cells were cocultured with BMSCs-Exo and ML385 (an inhibitor of Nrf2) in vitro. BMSCs-Exo may significantly improve the survival rate of the random flaps by reducing apoptosis, inflammation, and OS while increasing angiogenesis. Besides, BMSCs-Exo can also increase mitochondrial membrane potential and reduce reactive oxygen species levels in vitro. These therapeutic effects might stem from the activation of the Kelch-like enyol-CoA hydratase (ECH)-associated protein 1 (Keap1)/Nrf2 signaling pathway. BMSCs-Exo improved the tissue antioxidant capacity by regulating the Keap1/Nrf2 signaling pathway. BMSCs-Exo may be a new strategy to solve the problem of random flap necrosis.

Preconditioning Local Injection of Activated Platelet-Rich Plasma Increases Angiogenesis, VEGF Levels, and Viability of Modified McFarlane Flap in Diabetes-Induced Rats.

Background The risk of flap necrosis in tissue reconstruction surgery is elevated in patients with vascular disorders, such as diabetes mellitus. Chronic hyperglycemia causes endothelial cell dysfunction and increases inflammatory process, causing vascular insufficiency. Platelet-rich plasma (PRP) contains high levels of platelets, growth factors, and fibrinogens. Its regenerative properties spark interest in supporting flap survival in relation to diabetic complications. Methods Thirty Wistar rats were divided into three groups. The first group included diabetic rats without PRP injection, which underwent flap procedure. The second group included diabetes-induced rats receiving PRP subcutaneous injection 1 day prior to flap procedure. The third group included nondiabetic rats receiving PRP injection 1 day prior to flap procedure. Flap tissue samples were taken on the seventh day to measure vascular endothelial growth factor (VEGF) levels using enzyme-linked immunosorbent assay method; angiogenesis and collagen density were measured from histopathology examination, and flap viability was analyzed using digital measurements. Results Analysis showed that flap viability, angiogenesis, and VEGF levels were significantly higher in the PRP-injected diabetic rats compared with diabetic rats that did not receive PRP. The levels of VEGF, angiogenesis, and viability of flaps in diabetic rats given PRP did not differ significantly compared with nondiabetic rats that received PRP. Conclusion Flap preconditioning through local injection of activated PRP enhances flap viability, VEGF levels and angiogenesis, in random skin flaps in diabetic rats, to the level where it does not differ significantly to nondiabetic rats that were given PRP.

Experimental study of slow-released Angiogenin by silicon micro-needle in improving blood support to multiple-territory perforator flaps in rats.

This research aimed to investigate the effect of slow-released angiogenin by silicon micro-needle on angiogenesis in the Choke zone of dorsal multiple-territory perforator flap in rats, as well as its mechanism. Thirty-six adult Sprague-Dawley (SD) rats were randomly divided into control group, model group, and four experimental groups. In model group, slow-release saline through a silicon micro-needle was placed in choke II zone of the flap 7 days before the operation. For rats in four experimental groups, angiogenin was released via micro-needle in the choke I and choke II zones of the cross-zone flap 7 days before and 3 days before flap surgery, respectively. A 12 cm × 3 cm cross-zone perforator flap model was made on the back of all five groups. The flap survival rate in slow-release angiopoietin group was statistically higher than that in model group (P<0.05). Angiogenin in choke zone of the flap was increased in slow-release angiogenin group (P<0.05). In slow-release angiogenin group, the micro-vessel density was increased and the arteriovenous diameter was decreased, while the arteriovenous diameter was increased in model group (P<0.05). The levels of vascularendothelialgrowthfactorA (VEGF-A) and angiotensin 1 (ANG-1) in choke zone were both elevated in slow-release angiogenin group (P<0.05). The expression of CD31 was significantly elevated in flaps of experimental groups (P<0.05). Micro-needle to slow release Angiogenin can increase the drug concentration in the tissues of the choke zone, promote the vascularization of rat dorsal crossover area perforator flap, reduce the possibility of flap ischemic necrosis, and improve the flap survival rate.

In Vivo Engineering and Transplantation of Axially Vascularized and Epithelialized Flaps in Rats.

The arteriovenous loop (AVL) model allows the in vivo engineering of axially vascularized flaps, the so-called AVL flaps. Although AVL flaps can be transplanted microsurgically to cover tissue defects, they lack an epithelial layer on the surface. Therefore, the objective of this study was to engineer axially vascularized AVL flaps with an accompanying epithelial layer for local defect reconstruction. In this study, AVLs were established in 20 male Lewis rats. Minimally invasive injection of keratinocytes onto the surface of the AVL flaps was performed on postoperative day (POD) 21. AVL flaps were explanted from 12 rats on POD 24 or POD 30, then the epithelium formed by the keratinocytes on the surface of the flaps was evaluated using immunofluorescence staining. In six other rats, the AVL flap was locally transposed to cover a critical defect in the rats' leg on POD 30 and explanted for analysis on POD 40. In two control rats, sodium chloride was applied instead of keratinocytes. These control flaps were also transplanted on POD 30 and explanted on POD 40. Our results revealed that 3 days after keratinocyte application, a loose single-layered epithelium was observed histologically on the AVL flaps surface, whereas after 9 days, a multilayered and structured epithelium had grown. The epithelium on the transplanted AVL flaps showed its physiological differentiation when being exposed to an air-liquid interface. Histologically, a layered epithelium identical to the rats' regular skin was formed. In the sodium chloride control group, no epithelium had been grown. This study clearly demonstrates that axially vascularized AVL flaps can be processed in the subcutaneous chamber by minimally invasive injection of keratinocytes. Thus, AVL flaps with an intact epithelial layer were engineered and could be successfully transplanted for local defect coverage in a small animal model.

Thymosin β4 improves the survival of cutaneous flaps of rats and activates the Wnt/β-catenin pathway.

Thymosin β4 improves the survival of cutaneous flaps of rats and activates the Wnt/β-catenin pathway.

Effect of adipose tissue-derived stromal vascular fraction on the viability of random-pattern skin flaps: an experimental study

Aims: Random pattern skin flaps are still widely used in plastic surgery. However, necrosis in distal flap sections resulting from ischemia is a serious problem, increasing the cost of treatment and hospitalization. The aim of this study was to test the effects of adipose tissue derived stromal vascular fraction (SVF) on random pattern skin flaps in rats. Methods: In this experimental study conducted on Wistar rats, three groups were formed using the simple random sampling technique. Group 1 consisted of rats with a raised flap and a subcutaneous SVF injection. Group 2 comprised rats that underwent a flap operation with no additional treatment. Group 3 included rats with a raised flap and a subcutaneous saline injection. Tissue necrosis and level of survival area was detected with planimetric method and histopathologic examination was performed for detect of level of vascular density. On the 7th day post-operation, the viability assessment was calculated based on the ratio of the living flap area to the total flap area. Results: The mean viability rate in Group 1 was higher compared to other groups, while there was no significant difference between Group 2 and Group 3 (Group 1 = 79.2 ± 4.9 % vs. Group 2 = 41.0 ± 5.9 % vs. Group 3= 39.2 ± 2.7 %, p &lt; 0.001). The mean vascular densities of the flaps were higher in Group 1 compared to the other groups, while it were similar between Group 2 and Group 3 (Group 1 = 29.8 ± 1.2 vs. Group 2 = 8.4 ± 4.6 vs. Group 3= 9.3 ± 1.8, p &lt; 0.001). Conclusion: The use of fat tissue-derived SVF injections has been found to be advantageous in improving the survival of random pattern flaps, frequently utilized in plastic and reconstructive surgery.

Evaluate the effect of the metranidazole gel on healing of partial thickness flap in rats (serum TNF-a)

Background: Metronidazole is a broad-spectrum antimicrobial activity against protozoan infections and anaerobic bacteria. In the late 1950s, Metronidazole was first introduced for the treatment of trichomoniasis. At present, the antimicrobial metronidazole is one of the most widely used as antibacterial compounds in the treatment of periodontal disease 9. Beside the periodontal pocket debridement (subgingival scaling and curettage), topical application of metronidazole seems to be very efficacious. Metronidazole efficiently inhibited anaerobic microorganisms in the periodontal pockets 10.&#x0D; Objective: Evaluating the effect of metronidazole gel into surgically healing process of the partial thickness flap, throughout immunological study and comparing it with the chlorhexidine gel&#x0D; Animals and methods: The present study was carried out in Hawler Medical University, Medical research center, College of Dentistry&#x0D; Chemicals and Reagents:- (Rat TNF-a ELISA) kit for estimation of serum tumor necrosis factor (TNF-a), KOMA BIOTECH INC. USA)

Protective effect of bone marrow mesenchymal stem cells on the survival zone of the perforator flaps in rats.

Perforator flaps have recently been used in the field of plastic surgery. Skin defects can be reconstructed to reach functional and cosmetic goals. With the development of reconstructive approaches, utilizing stem cells is a hopeful approach to enhance wound healing and tissue recovery. In this study, we assessed the effect of bone marrow mesenchymal stem cells on the perforator flap's survival in rats. Perforator flaps (2.5 × 11 cm) were transplanted into rats and focused on the thoracodorsal, intercostal, and deep circumflex arteries, which were randomly divided into three groups: control, saline, and bone marrow mesenchymal stem cells (7 × 106 ml). Seven days after the surgery, tissue edema, inflammation, and discharge were observed and photographed. Histological analyses were performed to determine flap survival. Hematoxylin and eosin staining was performed to assess levels of microvascular density determined in skin flaps. Rats in the bone marrow mesenchymal stem cells group exhibited higher average flap survival area, and higher microvascular density levels at the dynamical regions of the flaps compared with the other two groups. Subdermal injection of bone marrow mesenchymal stem cells significantly increased ischemic perforator flap survival due to stimulated neovascularization in rats. Our findings suggest the potential usefulness of bone marrow mesenchymal stem cells in preventing skin flap perforator tissue necrosis.

Evaluation of enteral and parenteral hyaluronic acid in induced ischemic skin flaps in rats: a double-blinded and randomized study.

To evaluate exogenous hyaluronic acid (HA) derived from bacterial fermentation through enteral and parenteral routes in ischemic skin flaps induced in rats, using clinical and histological exams; and interleukins (IL) as tissue inflammatory biomarkers. Sixty-four male adults Wistar rats with ischemic skin flaps on the dorsum were randomized into four groups, based on the treatment protocol: subcutaneous administration of saline solution (0.9%) (GI); oral administration of distilled water (GII); subcutaneous administration of HA (0.3%) (GIII); and oral administration of HA (1%) (GIV). Flaps of all groups were comparable regarding clinical and macroscopic evaluation, histological examination, pro-inflammatory cytokines (IL-1β, IL-6, and tumor necrosis factor-α) and anti-inflammatory cytokine IL-10. A lower percentage of necrosis was identified in flaps treated with subcutaneous administration of HA (0.3%). The pro- and anti-inflammatory cytokines, epidermis thickness, blood vessels, and inflammatory cells showed statistically significant inter-group and intra-group differences (p < 0.05). High molecular HA (1,400 ~ 2,000 kDa) administrated by subcutaneous or oral route exhibited beneficial effects in ischemic skin flaps of rats. However, subcutaneous administration of HA (0.3%) showed better results in terms of the percentage of necrosis and epithelialization.

Systemic allopurinol administration reduces malondialdehyde, interleukin 6, tumor necrosis factor α, and increases vascular endothelial growth factor in random flap Wistar rats exposed to nicotine.

Smoking poses a risk to flap viability, with nicotine being a major contributor to the formation of free radicals. Allopurinol, known for its antioxidant properties, has been shown to enhance tissue survival in ischemic conditions by reducing the production of reactive oxygen species (ROS). This study aims to assess the impact of allopurinol on the viability and success of skin flaps in Wistar rats exposed to nicotine. This study examined skin flap survival in nicotine-exposed rats treated with allopurinol. Twenty-eight rats were separated into two groups. During 1 month of nicotine exposure, the treatment group received systemic allopurinol 7 days before and 2 days after the flap procedure, while the control group received no allopurinol. Pro-angiogenic factors, proinflammatory factors, anti-inflammatory factors, and oxidative markers were assessed on the 7th day after the flap procedure using enzyme-linked immunosorbent assay method. Macroscopic flap viability was evaluated on the 7th day using Image J photos. As an oxidative marker, malondialdehyde levels were significantly lower in rats given allopurinol than in controls (P &lt; 0.001). The levels of interleukin 6 and tumor necrosis factor α, as markers of inflammatory factors, were significantly lower in the group of rats given allopurinol compared to controls (P &lt; 0.001). The level of angiogenesis in rats given allopurinol, measured by vascular endothelial growth factor levels, was also higher in the treatment group compared to controls (P &lt; 0.001). Macroscopically, the percentage of distal flap necrosis in Wistar rats given allopurinol was lower and statistically significant compared to controls (P &lt; 0.001). Xanthine oxidoreductase is part of a group of enzymes involved in reactions that produce ROS. Allopurinol, as an effective inhibitor of the xanthine oxidase enzyme, can reduce oxidative stress by decreasing the formation of ROS. This reduction in oxidative stress mitigates the risk of ischemic-reperfusion injury effects and significantly increases the viability of Wistar rat flaps exposed to nicotine.

Protective effect of nitroglycerin ointment and dimethyl sulfoxide on necrosis of skin flaps in rats.

To compare the protective effect of nitroglycerin ointment 2% and Dimethylsulfoxide (DMSO) in dorsal flaps of the rat. A blind, experimental study was conducted in 24 male Wistar rats, with a mean weight of 320 (286-376) grams. Group 1: Control. Petrolatum jelly (Vaseline), n = 8, Group 2: Nitroglycerin (NTG) ointment 2% (Nitro-Bid, Altana Co.) n = 8, and Group 3: DMSO gel 90% (Neogen corp. Lexington KY, 40611), n = 8. A total of 24 rats were operated on in the 6-month period of this study. Using a non-parametric Mann-Whitney U-test analysis, a statistically significant p was obtained between the control group and 2% NTG ointment, both in the area of necrosis and in the healthy area (p = 0.026). In contrast, the comparison between DMSO [CH3) 2SO] and the control group (p = 0.180) and between both study groups, with a p = 0.18, was not significant. Our study concluded that there is a protective effect of 2% NTG ointment for flap survival in relation to the control group (petrolatum). DMSO administered topically did not show a protective effect, compared to the control group.

Ascorbic acid and calcitriol reduce TNF-α to improve the viability of modified McFarlane random skin flaps in Wistar rats

Link of Video Abstract: https://youtu.be/8UIEdUv8za8 Introduction: Distal flap necrosis is one of the most common complications in flap procedure. Ascorbic acid (vitamin C) is one of the most widespread antioxidants available, while calcitriol, a metabolite of vitamin D, has anti-inflammatory and antioxidant properties. The purpose of this study was to determine the effect of ascorbic acid and calcitriol on the viability of Modified McFarlane random skin flaps in Wistar rats and its mechanism through suppression of proinflammatory cytokine Tumor Necrosis Factor-α (TNF-α). Methods: An experimental study used 28 Wistar rats, by creating a caudally based 3 cm x 9 cm Modified McFarlane random skin flap and divided into four groups. The first group was injected with 200 mg/kg/day ascorbic acid, the second group with 2μg/kg/day calcitriol, and the third group with 200 mg/kg/day ascorbic acid combined with 2μg/kg/day calcitriol was injected two hours after flap elevation for seven days, respectively. The control group was not given any intraperitoneal injection. After seven days, the percentage of flap viability rate was measured and tissue sampling was performed to measure the amount of capillary density and TNF-α in all groups. Results: The higher percentage of viable flap area was found in all treatment groups, the highest in the ascorbic acid group 80.63% (p&lt;0.001). The highest capillary density was found in ascorbic acid combined with the calcitriol group (27/visual field, p&lt;0.001) compared to all groups. It was also found that the amount of TNF-α in the tissue was lowest in the group administered by ascorbic acid combined with calcitriol compared to all groups 57.38 ng/L and 0.62 nmol/mL respectively compared to all groups (p&lt;0.001). The higher percentage of viable flap area was correlated with a lower amount of TNF-α (p&lt;0.001), but not correlated with the amount of capillary density (p&gt;0.05). Conclusion: Ascorbic acid in combination with calcitriol improves the viability of Modified McFarlane random skin flaps by lowering TNF-α levels.

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.

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.

Effect of adipose derived stem cells on the survival rate of long random pattern skin flap in rats, and the underlying mechanism of action

Purpose: To investigate the effect of adipose-derived stem cells (ADSCs) on the survival rate of long random pattern skin flaps in rats and the likely underlying mechanism.&#x0D; Methods: Twenty (20) SPF-grade SD rats were randomly divided into control group and study group, with 10 rats in each group. Rats in the control group were given phosphate buffered saline (PBS), while rats in the study group received ADSCs. The survival rate of the skin flaps was compared between the 2 groups on day 7 after operation, while the levels of indices related to oxidative stress and inflammatory response were compared on the 7th and 14th days after operation.&#x0D; Results: Necrosis in the study group was milder (p &lt; 0.05). On the 7th post-operation day, the survival rate of rat skin flap in the study group was significantly higher than that in the control group (p &lt; 0.05), but the MDA level in the study group was lower than that of the control group (p &lt; 0.05). On the 14th day after the operation, the MDA level was decreased in the two groups (p &lt; 0.05), with a lower MDA level in the study group than in the control group (p &lt; 0.05).&#x0D; Conclusion: ADSCs inhibit inflammatory response and reduces the level of oxidative stress after long random pattern skin flap transplantation in rats, thereby enhancing blood supply to the flap transplantation area and improving its survival rate. Thus, ADSCs have a potential clinical application in enhancing blood supply in skin transplantation.

High-pressure infusion improves multi-territory perforator flap viability via choke artery dilation: A preliminary study in a rat model

Multi-territory perforator flaps have become the preferred option for the repair and reconstruction of large soft tissue defects. Although methods (e.g., pharmacological agents, mechanical stimulation, and thermal stimulation) were developed to open choke vessels to improve flap survival, the flap necrosis rate is still as high as 28.8%. The authors hypothesized that high-pressure infusion might enhance flap viability by dilating choke arteries intraoperatively in a rat model of multi-territory perforator flap. Two-month-old male Sprague-Dawley rats were randomized into two groups (n=32 each). During the multi-territory perforator flap elevation based on the right superficial epigastric angiosome, one group received continuous high-pressure infusion (mean pressure, 250mmHg; duration, 1min) of an isotonic heparin sodium solution (12,500U/L) via the artery in the pedicle, whereas the other group received no infusion. At 7 days postoperatively, arteriography was performed; endothelial nitric oxide synthase (eNOS) and vascular endothelial growth factor (VEGF) expression and microvascular density were evaluated by western blot and histology, respectively; and flap survival was compared. Moreover, intraluminal diameters were examined at 1day and 7 days postoperatively using hematoxylin and eosin staining, and coagulation function was assessed immediately postoperatively. High-pressure infusion significantly promoted the dilation of choke arteries at 1day and 7 days postoperatively. It also increased eNOS and VEGF expression, flap survival, and microvascular density. The coagulation function remained unaffected. High-pressure infusion allowed intraoperative and postoperative dilation of the choke arteries that enhanced the viability of multi-territory perforator flaps in rats.