Skin Flap Survival Research Articles

Increased survivability of ischemic skin flap tissue in Flk-1+/- mice by Pellino-1 intervention.

Reduced skin flap survival due to ischemia is a serious concern during reconstructive cosmetic surgery. The absence of VEGF and its receptors during ischemia may lead to flap failure. We identified Peli1, a 46-kDa protein, as a proangiogenic molecule and is directly regulated by VEGF. Therefore, we hypothesized that Peli1 acts downstream of Flk-1/VEGFR2 and aids in skin flap survival during ischemia. Scratch and matrigel assays were performed to observe cell proliferation, migration, and tube formation in vitro. Western blot analysis was carried out to detect the phosphorylation of Akt (p-Akt) and MAPKAPK2 (p-MK2) in HUVECs. The translational potential of Peli1 pretreatment in the rescue of skin flap tissue was studied in vivo using Flk-1+/- mice. Animals underwent dorsal ischemic skin flap surgery, and the tissue was collected on day 12 for analysis. Western blot analysis revealed a direct relationship between Peli1 and VEGF, as demonstrated by loss-of-function and gain-of-function studies. In addition, pretreatment with Ad.Peli1 restored the phosphorylation of Akt and MK2 and improved the migration potential of Flk-1-knockdown cells. Ad.Peli1 pretreatment salvaged the ischemic skin flap of Flk-1+/- mice by increasing blood perfusion and reducing the inflammatory response and the extent of necrosis. Our findings reveal that Peli1 is a proangiogenic molecule that acts downstream of VEGF-Flk-1 and restores angiogenesis and enhances skin flap survivability.

Effects of gamma-low dose irradiation on skin flap survival in rats

PurposeSkin flap necrosis due to inadequate blood supply has remained a common postoperative problem in constructive surgery. As low-dose irradiation (LDI) has been shown to promote the wound-healing process, this study aims to investigate whether LDI could increase neovascularization and skin flap survival in rats. MethodsMcFarlane flaps were created in 21 male rats, which were divided into one control and two treatment groups (Ta and Tb). The treatment groups received a whole body single dose of 100cGy gamma ray irradiation before (Tb) and after (Ta) flap surgery. The flap survival area was evaluated after seven days. The skin samples were collected for histological analysis and determining the vascular endothelial growth factor (VEGF) using the immunohistochemical method. Serum malondialdehyde (MDA) was examined with the kit. ResultsThe mean areas of flap survival were 56.7±3.24, 61.7±2.6, and 66.5±3.82 in the control, Tb, and Ta groups, respectively. There were significant differences between the Tb and Ta groups in comparison with the control group (P<0.05 and P<0.01, respectively). Compared with the control group (8.0±0.73), the mean numbers of the blood vessels in the Ta group (22±1.24) and the Tb group (14±1.29) were significantly higher (P<0.001 and P<0.01). Moreover, the mean numbers of the VEGF-positive cells in the Ta group (4.5±1.04) were significantly higher (P<0.05) than the control group (2.5±0.83). However, no significant differences in the MDA levels were observed among the groups. ConclusionThe findings of this study suggest that LDI has the potential to promote neovascularization to improve flap survival.

Effects and related mechanism of bivalirudin on the survival of random skin flap on the back of rat

Objective: To investigate the effects and related mechanism of bivalirudin on the survival of random skin flap on the back of rat. Methods: Thirty SD rats were divided into bivalirudin group and normal saline group according to the random number table, with 15 rats in each group. The random flap model with size of 9 cm×3 cm was reproduced on the back of rats in two groups. Immediately post injury, rats in bivalirudin group were intraperitoneally injected with 5 mg/mL bivalirudin (0.8 mL/kg), while rats in normal saline group were intraperitoneally injected with normal saline (0.8 mL/kg) once a day. The continuous injection lasted for 7 days. The flap was divided into distal area, middle area and proximal area averagely based on the flap blood supply. On post injury day (PID) 1, 3, and 7, the overall survival of each area of flap was observed with naked eyes. On PID 7, the survival rate of flap was calculated, and then the morphology of skin tissue at the center of the three areas of flap was observed by HE staining, the microvessel density (MVD) of the middle area of flap was calculated, and the expression of vascular endothelial growth factor (VEGF) of the middle area of flap was detected with immunohistochemical staining. Data were processed with t test. Results: (1) On PID 1, flaps of rats in two groups had different degrees of swelling, mainly concentrated in distal area, but there was no obvious necrosis. The middle area and proximal area of flaps in two groups were survived. On PID 3, the necrosis of flaps of rats in two groups was concentrated in the middle area, while the proximal area of flap was still in survival state, and most distal area of flap was necrosis with a little scab. On PID 7, the necrosis of middle area of flaps of rats in two groups was gradually fused, and the survival area of flap of rats in bivalirudin group was larger than that in normal saline group. The distal area of flap was almost necrotic, and the proximal area of flap was almost survived. (2) On PID 7, the survival rate of flap of rats in bivalirudin group was (64±4)%, significantly higher than that in normal saline group [(45±3)%, t=13.49, P<0.01]. (3) On PID 7, the histological morphology of distal area of flap of rats in two groups was similar, the inflammatory cells were infiltrated abundantly, and tissue edema was obvious. A large number of new blood vessels appeared in the middle area of flap of rats in bivalirudin group, with the formation of collateral vessels, and basic dilation of new blood vessels was seen. There were fewer new blood vessels appeared in the middle area of flap of rats in normal saline group, and dilation of new blood vessels was not obvious. There was little inflammatory cells infiltration in the proximal area of flap of rats in two groups. Compared with that in normal saline group, tissue edema extent of proximal area of flap of rats in bivalirudin group was less, and expansion was observed in more blood vessels. (4) The MVD of middle area of flap of rats in bivalirudin group was (26±5)/mm(2,) significantly higher than that in normal saline group [(18±3)/mm(2,) t=5.43, P<0.05]. (5) The expression of VEGF of middle area of flap of rats in bivalirudin group was 6 534±384, significantly higher than that in normal saline group (4 659±448, t=12.31, P<0.05). Conclusions: Bivalirudin can promote the survival of random skin flap in rats, and the mechanisms may include reducing the formation of thrombosis, improving the blood supply of flap, and increasing the expression of VEGF, promoting the formation of new blood vessels.

Effects of Shen-Fu injection on random skin flap survival in rats

ObjectiveThe aim of this study was to determine the effects of Shen-Fu injection treatment on skin flap survival in an experimental random pattern skin flap model in rats. Materials and methodsNinety male Sprague–Dawley (SD) rats were randomly assigned to the SFI-treated groups and normal saline-treated (control) group. SFI (10 or 20ml/kg) or normal saline (10ml/kg) were administered intraperitoneally once daily. On postoperative day 2, malondialdehyde (MDA), superoxide dismutase (SOD), tumor necrosis factor α (TNF-α) and IL-6 were evaluated. Besides, flap survival rate, tissue edema, mean vessel densities, number of neutrophil, flap angiography and vascular endothelial growth factor (VEGF) expression were examined on day 7. ResultsCompared with the control group, the mean survival area in SFI groups were significantly larger showing a possible dose-dependent effect of SFI. SOD activity was increased significantly, as well as the VEGF expression. MDA level, in the test group, however, was decreased. The hematoxylin and eosin (H&E) stained slices revealed that SFI had the angiogenesis promotion effect, meantime inflammation was clearly inhibited in the SFI groups. ConclusionThis study showed that intraperitoneally administered SFI significantly improved random skin flap survival in rats.

Inflammatory response associated with choke vessel remodeling in the extended perforator flap model.

Ischemic necrosis of the surgical flap is a common complication. The behavior of choke vessels has an important role in skin flap survival. However, the mechanism of choke vessel remodeling has remained elusive. The purpose of the present study was to investigate the possible association between inflammatory responses and choke vessel remodeling in the extended perforator flap model in rats. After flap elevation, the animals were randomly divided into three groups (n=6 in each) for tissue analysis at three, five or seven days after flap surgery. Six additional rats served as a control group (no flap elevation). Tissue samples were collected from the choke zone for histological, western blot and PCR analyses. Monocyte chemoattractant protein-1 (MCP-1) and tumor necrosis factor-α (TNF-α) as inflammatory cytokines were examined in the present study. Histopathological analysis showed that dilation of choke vessels and increased vessel wall thickness was obvious after flap elevation. It also showed edema, inflammation cell aggregation after the operation. Compared with the control group, the protein and mRNA expression levels of MCP-1 and TNF-α were significantly increased at days 3, 5 and 7 after flap elevation, while reaching a maximum at day 5. These findings indicated that inflammatory responses may have an important role in choke vessel remodeling. MCP-1 and TNF-α may be considered as potential targets for modulating the behavior of choke vessels.

Novel Injury Site Targeted Fusion Protein Comprising Annexin V and Kunitz Inhibitor Domains Ameliorates Ischemia-Reperfusion Injury and Promotes Survival of Ischemic Rat Abdominal Skin Flaps

The effects of ANV-6L15 on survival of rat abdominal fasciocutaneous flaps subjected to 10 hours of critical ischemia were assessed on day 5. Near-IR imaging was applied to evaluate the distribution of ANV-6L15 and flap perfusion. The rat cremaster muscle island flap was used to evaluate the effect of ANV-6L15 on IRI-induced leukocyte-endothelial interactions via intravital microscopy. 2,3,5 triphenyl-tetrazolium chloride assay was used to determine the ratio between live-versus-dead tissue. ANV-6L15 significantly increased the ratio of viable tissue (68.5 ± 9.79% vs 84.8 ± 5.14%, P < 0.05), and promoted survival of rat pedicled abdominal flaps (59.3 ± 6.86 vs. 47.0 ± 8.67, P < 0.05). Intravital microscopy demonstrated a significant decrease in the number of adhesive leukocytes (1.8 ± 1.64 vs. 10.0 ± 6.32, P < 0.05), and the percentage change of functional capillaries (16.4 ± 15.1 vs. 47.3 ± 18.3, P < 0.05) in ANV-6L15-treatment group. ANV-6L15 promoted survival of ischemic rat cremaster muscle and abdominal fasciocutaneous flaps and ameliorated leukocyte-related IRI. Future evaluation of potential clinical application of ANV-6L15 is warranted as a flap treatment adjunct.

Blood Congestion Can Be Rescued by Hemodilution in a Random-Pattern Skin Flap.

There is no standard method to ensure survival of random-pattern skin flaps. The authors developed a rat anemia model to observe survival of random-pattern skin flaps after blood transfusion and hemodilution. Anemia was induced by withdrawal of 35 percent blood volume followed by compensation with the same amount of blood (blood transfusion model) or plasma equivalent (normovolemic hemodilution). Control rats were subjected to a sham procedure. Subsequently, a random-pattern skin flap (1.5 × 6 cm) was elevated on the back of each rat. Physiologic assessments of flap vascularity/viability were performed using laser Doppler spectrophotometry before and after flap elevation. The normovolemic hemodilution group showed anemia (hemoglobin, 9.5 ± 0.8 g/dl) but less flow occlusion and greater flap survival (72.8 ± 8.6 percent) compared with control (57.4 ± 9.6 percent; p < 0.01) and blood transfusion (62.1 ± 6.5 percent; p < 0.089) groups. In control and blood transfusion groups but not the normovolemic hemodilution group, blood flow was decreased and relative quantity of hemoglobin was increased toward the flap tip, indicating congestion. In control and blood transfusion groups, blood flow and tissue oxygen saturation dropped after flap elevation, but recovered by day 7; congestion gradually improved by day 7. The authors determined that congestion promoted necrosis and hemodilution reduced microcirculatory occlusion and increased blood flow and oxygenation in skin flaps. It was suggested that perioperative hemodilution is superior to blood transfusion in any flap operations unless there is a critical systemic need for blood transfusion.

Effects of Traditional Chinese Medicine, Dilong Injection, on Random Skin Flap Survival in Rats

ABSTRACTBackground: Dilong injection as a medicinal preparation extracted from earthworm in traditional Chinese medicine, is used to activate blood circulation and remove blood stasis. In this research, we aim to investigate its potential effect on random skin flap survival in rat models. Materials and methods: McFarlane flaps were established in 60 male Sprague–Dawley rats randomly divided into two groups: the control group and the Dilong injection group. Diong injection group was injected with the Diong injection (4 mL/kg) once a day for seven days, and the control group was given an equal volume of saline solution. After seven days, flaps were obtained and stained with Hematoxylin and Eosin. Histological examination was done to determine changes in histology such as thickness of granulation tissue, tissue edema, neutrophil infiltration, and the microvascular density (MVD). In addition, immunohistochemical detection was carried out to show vascular endothelial growth factor (VEGF) expression level. Results: Compared with the control group, the Dilong group exhibited more fibroblastic proliferation, thinner neutrophil infiltration with less edema through histological examination. The MVD and the VEGF expression of flaps were significantly higher. The mean superoxide dismutase activity was evidently higher in the Dilong group than in the control group, while the mean MDA level was lower. Conclusions: According to the comparison made between the two groups for histological and immunohistochemical evaluation, the Dilong injection group has potential effects on the survival of random skin flaps in rat models.

Effect of botulinum toxin A on vasoconstriction and sympathetic neurotransmitters in a murine random pattern skin flap model

Blood supply is the most important factor determining the survival of a skin flap. Botulinum toxin-A (Botox-A) is used as pharmacologic agent not only for aesthetic purposes, but also for its vasomotor actions. This study was conducted to establish whether local application of Botox-A increased survival of random pattern skin flaps in rats by changing the expression of neurotransmitters. Forty adult Sprague-Dawley rats with a caudally-based random pattern skin flap were divided into two groups: Botox-A group and saline group. Surviving flap area and cutaneous blood flow in the flap were evaluated on postoperative days 3 and 7. After injection of Botox-A, changes in vessels were analyzed using immunohistochemical staining. Levels of norepinephrine, neuropeptide-Y, nitric oxide, and endothelial nitric oxide synthase were analyzed quantitatively by high performance liquid chromatography, Western blot, and colorimetric assay. The survived area in the Botox-A group was significantly higher than that in the control group on postoperative days 3 and 7. Blood flow in the Botox-A group was significantly high in the proximal and middle areas immediately after the operation. The number of CD31-positive vessels in the Botox-A group was significant greater than that in the control group. Norepinephrine level in the Botox-A group decreased significantly immediately after flap elevation and at postoperative day 3. There were no significant differences in neuropeptide-Y level between the two groups. Nitric oxide level did not change significantly in either group despite the increase in endothelial nitric oxide synthase immediately after flap elevation and at 3 days postoperatively. In conclusion, Botox-A increased vascular blood flow and viable flap area in rats by reducing norepinephrine level. In contrast, neuropeptide-Y, another vasoconstrictor, was not affected by Botox-A. Nitric oxide, a vasodilator, was also not affected by Botox-A, despite the significant increase in endothelial nitric oxide synthase expression in the flaps.

Effect of Systemic Antioxidant Allopurinol Therapy on Skin Flap Survival.

It has been reported that systemic administration of allopurinol improves cell survival. This study was aimed to evaluate effects of allopurinol on skin flaps in dogs.Twenty dogs underwent one skin flap surgery with a 2-week interval. The first procedure was performed according to the standard protocols. The second phase was started by a 1-week pretreatment with allopurinol. Length of the necrotic zone was measured and recorded daily. At each phase, flaps were removed and sent for histopathological study after 1 week observation.Mean length of the necrotic zone in allopurinol treated skin flaps has been significantly less than normal flaps over all 7 days of observation (p<0.0001). Histopathology study showed less inflammation and more normal tissue structure in the allopurinol treated skin flaps.It was demonstrated that systemic administration of allopurinol significantly improved skin flap survival.

Comparing the Effect of Hirudoid on Random Skin Flap Survival in Rats Based on Different Application Times

Objectives: The objective of the present study was to compare the use of Hirudoid immediately after surgery with its use 6 hours post-operatively when probable thrombosis was formed but tissue damage was still reversible. Methods: After preparing 3 × 11 cm dorsal flap in all rats, one group of 8 rats received Hirudoid topically immediately after surgery during 9 post-operative days. Another group received it 6 h after surgery during 9 post-operative days. The control group received Vaseline immediately after surgery on a daily basis during 9 post-operative days. Results: The mean area of flap survival in the control group was 8.75 ± 3.32 cm2 (mean ± SD) and it was 12.38±1.93 cm2 and 14.36 ± 3.51 cm2 in Hirudoid immediately after surgery and 6 hours after surgery groups, respectively. Conclusions: It was found that Hirudoid can be effective in improving flap viability; although its effect was not statistically significant when used immediately after surgery (P > 0.05), it significantly increased flap survival when used 6 h after surgery (P = 0.003).

Effect of propofol anesthesia on skin flap survival in rat; comparison with ketamine

Effect of propofol anesthesia on skin flap survival in rat; comparison with ketamine

Effectiveness of improved interosseous dorsal arteryisland flap cutting method to repair of hand trauma

Objective To research the clinical effect of the improved forearm interosseous dorsal flap cutting method to repair hand trauma. Methods Thirty-one cases patients with hand trauma who were treated in Dongfeng Hospital Affiliated to Hubei Medicine University from April 2014 to October 2015 were selected as study objects.Based on the improved interosseous artery after of the forearm interosseous dorsal flap cutting method to repair hand trauma, the skin flap survival after treatment and wound healing was observe. Results (1)Seven days after treatment, 2 cases of volar skin was defected flaps in patients with distal necrosis, and healed after the two phase of skin grafting, all the other flap issue of survival after the first phase, and the wounds were good, but there was 1 cases partial necrosis for skin grafting then healed after expectant treatment.(2)After 3-16 months follow-up, there were 4 cases of skin flap, and the appearance of the skin flap was over, and then the skin flap was repaired.The rest of the flap was good in appearance, and the two point discrimination was 5-8mm.(3)According to a 1994 Zhao Shuqiang improvements such as the luxury institute of Chinese medical association of functional trial evaluation standard of upper limb parts: 29 cases in excellent, 2 cases in good.All patients with hand trauma, skin color, appearance and perception function recovered satisfactorily. Conclusion The improved forearm interosseous dorsal flap cut operation is simple, flap survival situation better and wound healing, at the same time can also repair patients with hand perception function, is a kind of functional repair plan and worth promoting in clinic. Key words: Forearm interosseous dorsal skin flap; Hand trauma; Perceptive function; Functional reparation

Use of Systemic Rosmarinus Officinalis to Enhance the Survival of Random-Pattern Skin Flaps.

Skin flaps are commonly used in soft-tissue reconstruction; however, necrosis can be a frequent complication. Several systemic and local agents have been used in attempts to improve skin flap survival, but none that can prevent flap necrosis have been identified. This study aims to determine whether the use of systemic Rosmarinus officinalis (R. officinalis) extract can prevent flap necrosis and improve skin flap recovery. Animal experimentation. Thirty-five Wistar albino rats were divided in five groups. A rectangular random-pattern flaps measuring 8×2 cm was elevated from the back of each rat. Group I was the control group. In Group II, 0.2 ml of R. officinalis oil was given orally 2h before surgery. R. officinalis oil was then applied orally twice a day for a week. In Group III, R. officinalis oil was given orally twice a day for one week before surgery. At the end of the week, 0.2 mL of R. officinalis oil was given orally 2 h before surgery. In Group IV, 0.2 mL of R. officinalis oil was injected subcutaneously 2 h before surgery. After the surgery, 0.2 mL R. officinalis oil was injected subcutaneously twice a day for one week. In Group V, 0.2 mL R. officinalis oil was injected subcutaneously twice a day for one week prior to surgery. At the end of the week, one last 0.2 mL R. officinalis oil injection was administered subcutaneously 2 h before surgery. After the surgery, 0.2 mL R. officinalis oil was injected subcutaneously twice a day for one week. The mean percentage of viable surface area was significantly greater (p<0.05) in Groups II, III, IV, and V as compared to Group I. Mean vessel diameter was significantly greater (p<0.05) in Groups II, III, IV, and V as compared to Group I. We have determined that, in addition to its anti-inflammatory and anti-oxidant effects, R. officinalis has vasodilatory effects that contribute to increased skin flap survival.

Effects of the order of individual liquid on the survival of skin flap in patients after free flap transplantation

Objective To investigate the effects of the order of individual liquid on the survival of skin flap in patients after free flap transplantation. Methods From March 2013 to March 2016, 102 patients with trauma in extremities and underwent free flap transplanation in our hospital were randomly assigned to the study groupand the control group, with 51 cases in each group. Patients in the study group were treated with adjusted liquid order according to physiological and biochemical indexes. Patients in the control group were treated according to the order of medical orders. The occurrence of vascular crisis 48 h after operation and flap necrosis that 10 days after free flap transplantation were compared. Results 48 h after operation, there were 6 cases of postoperative vessel thrombosis and 3 cases of necrosis in the study group(χ2=5.795, P<0.05). 10 d after operation, there were 11 cases of postoperative vessel thrombosis and 3 cases of necrosis in the control group (χ2=5.299, P<0.05). Conclusions The individualized order liquid infusion can effectively reduce the occurance rate of vascular crisis and necrosis after free flap transplantation. Key words: Graft survival; Free flap; Vascular crisis; Necrosis; Order of individual liquid

Electrospun Photocrosslinkable Hydrogel Fibrous Scaffolds for Rapid In Vivo Vascularized Skin Flap Regeneration

Distal necrosis of random skin flap is always clinical problematic in plastic surgery. The development of 3D functional vascular networks is fundamental for the survival of a local random skin flap. Herein, an effective technique on constructing 3D fibrous scaffolds for accelerated vascularization is demonstrated using a photocrosslinkable natural hydrogel based on gelatin methacryloyl (GelMA) by electrospinning. It is found that the ultraviolet (UV) photocrosslinkable gelatin electrospun hydrogel fibrous membranes exhibit soft adjustable mechanical properties and controllable degradation properties. Furthermore, it is observed that the optimized hydrogel scaffolds can support endothelial cells and dermal fibroblasts adhesion, proliferation, and migration into the scaffolds, which facilitates vascularization. Importantly, a rapid formation of tubes is observed after 3 d seeding of endothelial cells. After GelMA fibrous scaffold implantation below the skin flap in a rat model, it is found that the flap survival rate is higher than the control group, and there is more microvascular formation, which is potentially beneficial for the flap tissue vascularization. These data suggest that GelMA hydrogels can be used for biomedical applications that require the formation of microvascular networks, including the development of complex engineered tissues.

Favorable effects of progesterone on skin random flap survival in rats.

The aim of this study is to determine the effects of progesterone treatment on the survival of random skin flaps. McFarlane flaps were established and 40 male rats were randomly assigned to the progesterone-treated as the test group or normal saline-treated as the control group. Progesterone or normal saline (10 mg/kg) was administered intraperitoneally once daily. On postoperative day 2, malondialdehyde (MDA) and superoxide dismutase (SOD) were detected using test kits. Flap survival rates were evaluated with transparent graph paper under direct visualization, the levels of inflammation were examined by haematoxylin and eosin (H&E) staining, and the expression of vascular endothelial growth factor (VEGF) was immunohistochemically evaluated on day 7. Compared to that in the control group, the mean survival area was significantly larger in the progesterone group. SOD activity was increased significantly, but the MDA levels in the test group were decreased. H&E-stained slices revealed that inflammation was inhibited in the test group. VEGF expression markedly increased in the progesterone group. This study showed that progesterone administered intraperitoneally significantly improved random skin flap survival in rats.

The Nipple-Areola Preserving Mastectomy: The Value of Adding a Delay Procedure.

Background:Conservative mastectomy procedures, such as the nipple-sparing mastectomy (NSM), present appealing options for patients with small invasive or noninvasive malignancies and those needing prophylactic mastectomies. Despite outstanding postoperative cosmetic results, nipple–areola complex (NAC) and mastectomy skin flap (MSF) survival remains a concern. We present our two-stage nipple–areola preserving (NAP) mastectomy, which aims to decrease the rate of NAC loss and MSF necrosis after conservative mastectomies.Material and Methods:Seventy patients who underwent NSM because of malignant and benign conditions were divided into 2 groups: those who underwent our two-stage NAP mastectomy were matched to the group of mastectomy patients without preservation techniques. Demographic data and postoperative results were retrospectively assessed.Results:The NAP group comprised 45 flaps (24 patients), and the NSM group comprised 75 flaps (46 patients). None were actively smoking. The mean time between the delay of the flap and breast reconstruction was 17.6 days (range, of 10–35 days) in the NAP group. No signs of NAC vascular compromise were observed in the NAP group. Nipple necrosis rates were significantly greater (P = 0.0136) in the NSM group: 9 cases in the NSM group versus none within the NAP group. Two patients within the NAP group required nipple excision at the time of their mastectomies after biopsies performed at the time of the NAC delay were positive for malignancy or atypia.Conclusions:Vascular delay techniques favor the blood supply of a tissue after a surgical wound, effectively improving the survival of the NAC and MSF after nipple-sparing mastectomies.

EFFECTS OF Tempol ON SURVIVAL OF RANDOM PATTERN SKIN FLAPS IN RATS

To study the effects of the new small molecular oxygen free radical scavenger Tempol on the survival and vasculogenesis of the long random pattern skin flap (LRPSF) and its mechanism. Eighty-four male Sprague Dawley rats were randomly divided into control and Tempol groups (42 rats in each group). LRPSF of 9 cm×3 cm in size were prepared on the backs of rats in two groups based on the Mcfarlane flap. Rats were administered with Tempol (100 mg/kg) in the Tempol group and with normal saline in the control group by intraperitoneal injection at 15 minutes before operation and at 1-7 day after operation. The rat and the skin flap survival conditions were observed after operation; the survival rate of skin flap was measured, and the vascular structure, vascular volume, and total length of blood vessels were analyzed with Micro-CT three-dimensional imaging after 7 days; HE staining was used to observe the structure of the skin flaps and inflammation, immumohistochemical staining to observe vascular endothelial growth factor (VEGF) expression; water-soluble tetrazolium-1 method was used to measure the content of superoxide dismutase (SOD) and malondialdehyde (MDA), and ELISA to detect the expressions of tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6) after 1, 3, and 7 days. All of rats survived after operation, without hemorrhage, edema, and infection. With the extension of time, necrosis occurred in the distal part of the skin flaps in 2 groups, but the necrosis degree of the Tempol group was lower than that of control group; meanwhile, the blood vessel distribution and continuity were better than those of control group. The skin flaps survival rate, vascular volume, and total length of blood vessels of Tempol group were significantly higher than those of control group after 7 days (P<0.05). The clearer skin flaps structure, lighter inflammation reaction and inflammation cell infiltration, and higher VEGF staining intensity were observed in the Tempol group than the control group after 7 days. There was no significant difference in SOD, MDA, and TNF-α, and IL-6 contents between the 2 groups at immediate after operation. SOD significantly increased, but MDA, TNF-α, and IL-6 contents significantly decreased in the Tempol group when compared with control group after 1, 3, and 7 days (P<0.05). Tempol can significantly promote the LRPSF survival rates, its mechanism is closely related to the promotion of vasculogenesis and reduction of oxidative stress and inflammation.

Role of the p38 mitogen-activated protein kinase signaling pathway in estrogen-mediated protection following flap ischemia-reperfusion injury.

Ischemia-reperfusion (I/R) injury often occurs during skin flap transplantation and results in tissue damage. Although estrogen treatment significantly alleviates this I/R injury-induced damage, the detailed molecular mechanism is not clear. In this study, a superficial epigastric artery flap I/R injury model was created in adult Wistar rats. Severe necrosis was observed in skin tissue after I/R injury. Histological examination of skin tissue revealed that I/R injury damages skin structure and results in neutrophil infiltration. Inflammation-related parameters, including neutrophil count, tumor necrosis factor-α, and interleukin-10 levels, were increased due to I/R injury. These pathological phenomena were reduced by estradiol treatment. Further investigation found that I/R injury triggers the p38 mitogen-activated protein kinase (p38-MAPK) pathway. The expression levels of p38-MAPK and phosphorylated p38-MAPK were increased after I/R injury. Estradiol increased the expression level of MAPK phosphatase-2, a putative phosphatase of p38, and reduced the levels of p38-MAPK and phosphorylated p38-MAPK. These results suggest that estradiol can improve skin flap survival, possibly by inhibiting neutrophil infiltration and the expression of p38-MAPK. This study provides an explanation for how estrogen alleviates I/R injury-induced damage that occurs during skin flap transplantation. In a rat pathological model, I/R injury leads to skin necrosis, skin structure damage, neutrophil infiltration, and inflammatory cytokine secretion, which are probably downstream effects of activation of the p38-MAPK pathway. On the other hand, estradiol treatment triggers the expression of MAPK phosphatase-2, a putative phosphatase of p38-MAPK, and reduced all examined pathological phenomena. Therefore, estrogen may reduce the deleterious effect of I/R injury on skin flap transplantation through modulating the p38-MAPK pathway.