The Effect of Postoperative Aspirin on Random Pattern Flaps in Rats

Our laboratory has been studying the effect of aspirin, given alone or in combination with other medications, on random pattern skin flaps. We have consistently found that preoperative aspirin in high doses (200 mg/kg) increases flap survival, apparently as a result of its ability to modify the inflammatory reaction and/or direct vasodilatation, and not as a consequence of antiaggregation of platelets. In an effort to further elucidate how this effect is modulated, we designed this experiment in which we gave aspirin after the operative procedure to simulate an acute clinical surgical problem such as a failing or ischemic flap. Our results failed to show any difference between the rats that received postoperative aspirin and the untreated control group. It would appear that aspirin given postoperatively is not able to counteract the noxious elements that affect flap survival. This work indicates an important relationship between the timing of administration and the beneficial effects of aspirin. By investigating fully the mechanism whereby aspirin is able to improve flap survival, we hope to isolate this mechanism so an alternative pharmacological agent, safer than aspirin, can be found for clinical use.

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Effects of natural and recombinant hirudin on superoxide dismutase, malondialdehyde and endothelin levels in a random pattern skin flap model

Journal of Hand Surgery (European Volume) ◽

10.1177/1753193411414628 ◽

2011 ◽

Vol 37 (1) ◽

pp. 42-49 ◽

Cited By ~ 5

Author(s):

Guo Ying-Xin ◽

Yin Guo-Qian ◽

Li Jia-Quan ◽

Xiao Han

Keyword(s):

Superoxide Dismutase ◽

Skin Flap ◽

Survival Rates ◽

Control Group ◽

Random Pattern ◽

Skin Flaps ◽

Recombinant Hirudin ◽

Flap Survival ◽

Treatment Groups ◽

Anti Inflammatory

We have assessed the anti-inflammatory, anti-oxidative and anti-coagulant effects of locally applied natural and recombinant hirudin in a random skin flap rat model. Thirty Wistar rats with venous congested skin flaps were randomly divided into two treatment groups and a control group to receive subcutaneous injections of natural hirudin (6 U), recombinant hirudin (6 U) or physiological saline, respectively. Superoxide dismutase, malondialdehyde and endothelin levels as well as flap survival rates of the skin flaps were measured after surgery. Compared to the control group, the treatment groups had significant higher superoxide dismutase levels and lower malondialdehyde and endothelin levels in the skin flaps. The surviving areas of the flaps were larger in the treatment groups than the control group. Our results demonstrated that hirudin could improve skin flap survival through its anti-inflammatory, anti-oxidative and anti-coagulant activities.

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

Cell Death and Disease ◽

10.1038/s41419-019-2105-0 ◽

2019 ◽

Vol 10 (12) ◽

Cited By ~ 2

Author(s):

Kailiang Zhou ◽

Huanwen Chen ◽

Jinti Lin ◽

Hui Xu ◽

Hongqiang Wu ◽

...

Keyword(s):

Signaling Pathways ◽

Nuclear Translocation ◽

Skin Flap ◽

Therapeutic Benefit ◽

Random Pattern ◽

Skin Flaps ◽

Flap Survival ◽

Ampk Signaling ◽

Flap Viability ◽

Mechanistic Investigation

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

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The Relationship of Hematocrit Levels to Skin Flap Survival Length in the Pig

Otolaryngology ◽

10.1177/019459988108900511 ◽

1981 ◽

Vol 89 (5) ◽

pp. 750-752 ◽

Cited By ~ 5

Author(s):

Jeffrey B. Alperstein ◽

Howard L. Levine ◽

Harvey M. Tucker

Keyword(s):

Human Skin ◽

Control Animal ◽

Skin Flap ◽

Random Pattern ◽

Skin Flaps ◽

Flap Survival ◽

Significant Difference ◽

Skin Flap Survival ◽

Relationship Of ◽

The Relationship

The work of several investigators suggests that anemia may increase the survival length of skin flaps in the dog and the rabbit. The following experiment was designed to study the survival of standardized skin flaps of varying lengths in normocythemic, polycythemic, and anemic pigs. The pig was chosen because of the similarity of its skin to that of human skin. Twenty-nine standardized random-pattern flaps and six standardized arterial flaps were studied in pigs with varying hematocrits. A statistically significant increase was found in the survival lengths of skin flaps in the polycythemic animal as compared with the anemic one. No significant difference was found when the flap survival lengths of the normocythemic control animal were compared with those of the polycythemic animal or with those of the anemic animal. These findings suggest that relative polycythemia may allow improved flap length-survival and, in contradistinction to the findings of previous investigators, that anemia does not result in improved survival length.

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

Acta Cirurgica Brasileira ◽

10.1590/s0102-86502010000500010 ◽

2010 ◽

Vol 25 (5) ◽

pp. 440-443 ◽

Cited By ~ 7

Author(s):

Gustavo Roberto de Godoy ◽

Richard Eloin Liebano ◽

Juliana Barbosa Corrêa ◽

Bernardo Hochman ◽

Lydia Masako Ferreira

Keyword(s):

Surgical Procedure ◽

Wistar Rats ◽

Skin Flap ◽

Donor Site ◽

Control Group ◽

Random Pattern ◽

Skin Flaps ◽

Flap Necrosis ◽

Group A

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

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Dimethyl Sulfoxide Increases the Survival of Primarily Ischemic Island Skin Flaps

Otolaryngology ◽

10.1177/019459989411000213 ◽

1994 ◽

Vol 110 (2) ◽

pp. 228-231 ◽

Cited By ~ 20

Author(s):

Ilsa Schwartz ◽

Robert J. Carpenter ◽

Michael F. Angel ◽

Raymond F. Morgan

Keyword(s):

Free Radical ◽

Dimethyl Sulfoxide ◽

Saline Solution ◽

Control Group ◽

Skin Flaps ◽

Ample Evidence ◽

Flap Survival ◽

Group 4 ◽

Significant Difference ◽

Group 3

There is ample evidence of the involvement of free radicals in mediating skin flap necrosis. Dimethyl sulfoxide (DMSO) is a well-tolerated, safe drug that is a powerful scavenger of the hydroxyl free radical. The current study investigated the effect of DMSO on the survival of 9 × 4 cm skin flaps based on the epigastric vessels subjected to primary venous occlusion. Forty-seven skin flaps were elevated and the epigastric vein was occluded by a microvascular clamp for 8 hours. Group 1 received DMSO (1.5 gm/kg) intraperitoneally at reperfusion. Group 2 received saline solution, group 3 received DMSO at reperfusion and every day for 5 days, group 4 received DMSO preoperatively and then as in group 3, and group 5 was the saline solution control for groups 3 and 4. DMSO did not increase percent flap survival when given as a single dose at reperfusion (40.6% ± 42.7%) compared with saline solution (33.7% ± 41.2%). When DMSO was continued in the postoperative period, group 3 (86.2% ± 25.8%) and group 4 (78.0% ± 32.5%) had significantly better survival than the saline solution control group (32.6% ± 39.8%) ( p < 0.01 and p < 0.03, respectively). There was no significant difference between groups 3 and 4. DMSO administered at reperfusion and postoperatively for 5 days significantly increased flap survival. It is hypothesized that this occurs through scavenging deleterious free radical species. This effect may have clinical significance.

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Gastrodin Promotes the Survival of Random-Pattern Skin Flaps via Autophagy Flux Stimulation

Oxidative Medicine and Cellular Longevity ◽

10.1155/2021/6611668 ◽

2021 ◽

Vol 2021 ◽

pp. 1-16

Author(s):

Hongyu Chen ◽

Baoxia Chen ◽

Baolong Li ◽

Xiaobin Luo ◽

Hongqiang Wu ◽

...

Keyword(s):

Oxidative Stress ◽

Underlying Mechanism ◽

Random Pattern ◽

Skin Flaps ◽

Common Complication ◽

Autophagy Flux ◽

Chinese Medicinal Herb ◽

Flap Survival ◽

Tissue Edema ◽

Easy Operation

The random-pattern flap has a significant application in full mouth restoration (reconstructive surgery) and plastic surgery owing to an easy operation with no axial vascular restriction. However, distal necrosis after flap operation is still considered the most common complication which makes it the Achilles heel in the clinical application of random-pattern flaps. A Chinese medicinal herb named gastrodin is an effective active ingredient of Gastrodia. Herein, the existing study explored the significant potential of gastrodin on flap survival and its underlying mechanism. Our obtained results show that gastrodin will significantly improve flap survival, reduce tissue edema, and increase blood flow. Furthermore, our studies reveal that gastrodin can promote angiogenesis and reduce the apoptotic process as well as oxidative stress. The results of immunohistochemistry and immunoblotting revealed that gastrodin has a role in the elevation of autophagy flux which results in induced autophagy. The use of 3MA (3-methyladenine) for the inhibition of induced autophagy significantly weakened the underlying benefits of gastrodin treatment. Taken together, our obtained results confirmed that gastrodin is an effective drug that can considerably promote the survival rate of flaps (random pattern) via enhancing autophagy. Enhanced autophagy is correlated with the elevation of angiogenesis, reduced level of oxidative stress, and inhibition of cell apoptosis.

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Assessment of Survival and Microscopic Changes in Porcine Skin Flaps Undergoing Immediate Intraoperative Tissue Expansion

Otolaryngology ◽

10.1177/019459989310900523 ◽

1993 ◽

Vol 109 (5) ◽

pp. 926-932 ◽

Cited By ~ 8

Author(s):

Roberta Guida ◽

James I. Cohen ◽

Ted A. Cook ◽

Neil A. Swanson ◽

Robert Burgeson ◽

...

Keyword(s):

Electron Microscopy ◽

Tissue Expansion ◽

Constant Load ◽

Ultrastructural Changes ◽

Random Pattern ◽

Elastic Tissue ◽

Skin Flaps ◽

Flap Survival ◽

Flap Viability ◽

Microscopic Change

The technique of rapid Intraoperative tissue expansion has been used with increasing frequency in the clinical setting over the last several years. This technique takes advantage of the skin's ability to immediately stretch and increase in surface area when expanded under a constant load. Sixteen random-pattern, rapidly expanded skin flaps on 10 domestic male pigs were studied to assess the predictive value of the fluorescein test for flap viability after rapid intraoperative tissue expansion. Partial fluorescence was found to be a more accurate predictor of flap survival in the experimental rapidly expanded flaps when compared to full fluorescence. Partial fluorescence was found to under-predict flap survival by 0.3 to 0.5 cm, whereas full fluorescence was found to under-predict flap survival by 2.5 cm. Additionally, histologic and ultrastructural changes were examined in rapidly expanded skin from the hip region in three pigs. The only microscopic change noted between control and experimental flaps was dilated capillaries in the dermis of expanded skin, which was noted by electron microscopy. Collagen and elastic tissue changes were not demonstrated in rapidly expanded pig skin by electron microscopy, direct immunoflurescence, collagen, and elastic tissue stains.

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Effects of Natural and Recombinant Hirudin on VEGF Expression and Random Skin Flap Survival in a Venous Congested Rat Model

International Surgery ◽

10.9738/cc171.1 ◽

2013 ◽

Vol 98 (1) ◽

pp. 82-87 ◽

Cited By ~ 10

Author(s):

Guo Yingxin ◽

Yin Guoqian ◽

Li Jiaquan ◽

Xiao Han

Keyword(s):

Rat Model ◽

Messenger Rna ◽

Skin Flap ◽

Survival Rates ◽

Control Group ◽

Skin Flaps ◽

Vegf Expression ◽

Recombinant Hirudin ◽

Flap Survival ◽

Skin Flap Survival

Abstract We aim to investigate the effects of locally injected natural and recombinant hirudin on vascular endothelial growth factor (VEGF) expression and flap survival in venous congested skin flaps using a rat model. A dorsal random skin flap (10 × 3 cm) was prepared on each of 30 Wistar rats to establish a venous congested model. The rats were randomly divided into 2 treatment groups [receiving subcutaneous injection of either natural hirudin (6 U) or recombinant hirudin (6 U)] and a control group, which received subcutaneous injection of physiologic saline. After treatment, skin flap survival rates were calculated. VEGF messenger RNA levels and VEGF-positive vessel density as a marker for VEGF levels were measured in the flaps during and after treatment. The skin flap VEGF messenger RNA levels increased in the natural hirudin-treated group. The VEGF-positive vessel density was increased in all 3 groups. Statistically significant increases of VEGF levels were observed in the natural and recombinant hirudin-treated groups compared with the control group (P < 0.05). The skin flap survival rates were improved in both hirudin treated groups. Natural and recombinant hirudin can increase VEGF expression in random skin flaps, which can potentially improve random skin flap survival in rats through angio genic mechanisms. Our results showed that hirudin treatment led to an increase in VEGF expression in the congested skin flaps. Natural hirudin demonstrated more pronounced effects than recombinant hirudin. Further studies are needed to understand the specific mechanisms.

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

Frontiers in Pharmacology ◽

10.3389/fphar.2021.653035 ◽

2021 ◽

Vol 12 ◽

Author(s):

Jingtao Jiang ◽

Jie Jin ◽

Junsheng Lou ◽

Jiafeng Li ◽

Hongqiang Wu ◽

...

Keyword(s):

Oxidative Stress ◽

Skin Flap ◽

Random Pattern ◽

Skin Flaps ◽

Flap Necrosis ◽

Tissue Samples ◽

Flap Survival ◽

Flap Viability ◽

Skin Flap Survival ◽

Positive Effect

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

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

Cell Death and Disease ◽

10.1038/s41419-019-1704-0 ◽

2019 ◽

Vol 10 (7) ◽

Cited By ~ 6

Author(s):

Hongqiang Wu ◽

Huanwen Chen ◽

Zhilong Zheng ◽

Jiafeng Li ◽

Jian Ding ◽

...

Keyword(s):

Oxidative Stress ◽

Nuclear Translocation ◽

Skin Flap ◽

Random Pattern ◽

Skin Flaps ◽

Major Pathway ◽

Flap Survival ◽

Flap Viability ◽

Tissue Edema ◽

Skin Flap Survival

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

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