Preoperative subcutaneous sildenafil injection increases random flap survival in rats

Serin, Merdan; Altınel, Dinçer; Leblebıcı, Cem; Biltekin, Burcu; Celikten, Mert; Irmak, Fatih; Yazar, Sevgi Kurt

doi:10.1590/s0102-865020180030000003

Cited by 10 publications

(10 citation statements)

References 21 publications

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“…This finding was in harmony with the results of Kaya et al 43 , Sarifakioglu et al 44 , Tsai et al 45 and Shah et al 8 who used sildenafil also as a treatment and concluded that sildenafil is able to improve skin flap survival in a dose-dependent manner. In contrast, Figueiredo et al 46 , Barral et al 47 , Serin et al 4 and Ayyildiz et al 11 had revealed that sildenafil does not affect skin viability. These negative data shown by those authors for sildenafil treatment may be due to the different doses or the different routes of administration that were used.…”

Section: Discussionmentioning

confidence: 94%

“…Despite its local application, NTG ointment exerts a systemic hypotensive effect 58 . Although previous publications have reported that sildenafil alone or NTG alone, as systemic vasodilator agents, could improve the viability rate of flaps, other publications suggest that most systemic vasodilators have no effect on the enhancement of skin flap survival, mostly because their systemic hypotensive effect results in decreased skin flap perfusion, leading to increased rates of necrosis 4,14,31,44,45,59,60 . Therefore, it is essential to adjust the doses, forms of application and duration of using the combination of sildenafil and NTG in patients undergoing skin flap reconstructive surgery to avoid the possible synergistic hypotensive effect of both agents on skin flaps.…”

Section: Discussionmentioning

confidence: 97%

“…Sildenafil is a phosphodiesterase type 5 enzyme inhibitor. Inhibition of this enzyme increases the cyclic guanosine monophosphate levels inside cells and the NO concentration in the surrounding environment, which in turn leads to vascular smooth muscle relaxation, vasodilatation, inhibition of platelet aggregation, an increased blood flow, stimulation of angiogenesis and a decreased severity of inflammatory reactions 4,41,42 .…”

Section: Discussionmentioning

confidence: 99%

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The Effects of Sildenafil and/or Nitroglycerin on Random-pattern Skin Flaps After Nicotine Application in Rats

Ellabban

Fattah

Kader

et al. 2020

Sci Rep

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Smoking aggravates skin necrosis as a complication of random-pattern flap ischaemia. Sildenafil and nitroglycerin (NTG) are vasodilator agents that may affect skin flap survival. Fifty rats were subjected to a dorsal random-pattern flap operation and randomly divided into 5 groups. The control group received no treatment. The ischaemic group were administered local nicotine injections. The sildenafil group were administered oral sildenafil treatment in addition to the same intervention as the ischaemic group. The NTG group received topical NTG ointment application instead of sildenafil. The combined group were given both sildenafil and NTG treatments. After 7 days, all rats were sacrificed for flap assessment. Flap survival percentages at the 3 rd and 7 th days were significantly higher in the combined group than in the other study groups. Histologically, the ischaemic group exhibited dermal disorganization and inflammatory cell infiltration, which were improved in the 3 treated groups; however, the combined group presented the most relevant effect. The epidermal thickness showed a decrease in the ischaemic group (23.1 μm) that was significantly increased in the sildenafil (28.4 μm), NTG (28.8 μm) and combined (35.8 μm) groups. Immunohistochemically, the combined group exhibited a significant decrease in the apoptotic index and an increase in the proliferative index (2.3 and 56.9%, respectively) compared to those in the ischaemic (63.2 and 3%), sildenafil (41.7 and 28.1%) and NTG (39.3 and 30.4%) groups. Transmission electron microscopy (TEM) showed that the combined group displayed improvement in most of the ischaemic changes. Our analyses suggest that the combined use of sildenafil and NTG is more efficacious than using only one of these treatments for skin flap survival.Random skin flaps are widely used options for the reconstruction of large acquired or congenital skin defects 1 . Survival of these flaps is highly reliant on oxygen delivery to their tissues 2 . The main challenge is that the distal parts of the flap suffer from a reduced blood supply, which can trigger skin necrosis 3 . This reduction in the blood supply is mainly caused by anatomical or haemodynamic factors 4 . During vascular regeneration, ischaemia/reperfusion injury occurs, promoting oxidative stress and apoptosis 3 . Additionally, other factors, such as inadequate angiogenesis and inflammatory reactions, play roles in the pathogenesis of flap necrosis 5 .Skin flap ischaemic necrosis and increased incidence of infection can be aggravated by nicotine, which endangers the results of plastic skin reconstruction 6 . Smoking increases the risk of skin flap complications, which has been observed in clinical and experimental studies in both rats and hamsters 7 . Smokers have a higher risk of developing skin flap necrosis, namely, 13 times higher than that of non-smokers, which can result in flap loss or secondary contractures that negatively affect the aesthetic outcomes 6,8 . The potential mechanisms of this increased risk in smokers are highly...

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Section: Discussionmentioning

confidence: 94%

Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

The Effects of Sildenafil and/or Nitroglycerin on Random-pattern Skin Flaps After Nicotine Application in Rats

Ellabban

Fattah

Kader

et al. 2020

Sci Rep

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“…28,30 PDE-5I have also been used to improve flap survival by improving vascularity in an animal study. 31 Kurt et al 11 used rat models to show urethral strictures could after urethral thermal injury be prevented with the use of tadalafil after urethral thermal injury. The study showed that, in the tadalafil group, the collagen deposition in submucosal connective tissue was significantly less, proving the protective effect against formation of urethral stricture.…”

Section: Type Of Redo Urethroplastymentioning

confidence: 99%

Redo pelvic fracture urethral injury repair: The case for tadalafil

Joshi¹,

Desai²,

Fuziwara³

et al. 2021

Turkish Journal of Urology

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Objective: To define the role of tadalafil in improving outcomes of redo urethroplasty for pelvic fracture urethral injury (PFUI). PFUI is common in developing countries, invariably as a result of road traffic trauma. Repair is complex, and redo cases are even more challenging.Material and methods: This was a longitudinal prospective nonrandomized study between 2017 and 2019. Men undergoing redo-urethroplasty were nonrandomized into two groups. Group 1 received tadalafil 5 mg the next day after surgery and continued for 3 months, and group 2 did not receive tadalafil. Inclusion criteria were patients undergoing redo-urethroplasty willing to trial low-dose tadalafil post-operatively. Exclusion criteria were <18 years, females, primary cases, and complex cases such as recto-urethral fistula. Average follow-up was 19.5 months.Results: Sixty patients were enrolled (29 in group 1 and 31 in group 2). Mean age was 31 years. These patients had 1-3 prior failed urethroplasties. Most required step 3 anastomotic urethroplasty (68.3%). Success was defined as absence of symptoms and no need for surgical intervention. Failure was defined as redo urethroplasty or >1 endoscopic intervention. Primary success was 83.3%. Success with tadalafil was 96.6%, compared to 71.0% in the non-Tadalafil group (P ¼ .0008). Only one patient on tadalafil failed, compared with nine in the non-tadalafil group. Secondary success rate was defined as the need for a single subsequent endoscopic intervention and was 93.3%. Conclusion:In our series, there was improved outcome with using tadalafil in patients having redo urethroplasty for PFUI. Further trials should be done to evaluate the use in all PFUI cases.

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“…Despite attempts to transfer tissue without damaging the blood supply, flaps may show signs of poor perfusion and venous congestion in sectioned vascular structures. Besides the complexity of the scarring process, flaps undergo a crucial phase in their viability due to the inherent changes during tissue transfer [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

Effects of sildenafil and tadalafil on skin flap viability

et al. 2021

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Vascular complication is one of the causes of skin flap healing failure. Sildenafil and tadalafil, a type-5 phosphodiesterase inhibitor, can improve flap viability, however, the action mechanisms involved in this process are still unclear. To assess the effects of orally administered sildenafil and tadalafil on the healing kinetics and skin flap viability, sixty-two Wistar rats were divided into three groups: control (n = 22), sildenafil (n = 20), and tadalafil (n = 20). The solutions were administered orally (dose: 10 mg/kg) immediately after the surgical procedure and then every 24 h. At postoperative days 7 and 14, the skin flap samples were collected, submitted to histological processing and evaluated under optical microscopy. In experimental groups (sildenafil and tadalafil), we found an increased vascularization (p < 0.05) on the 7th and 14th day associated with the ulcer size decrease on the 14th day, although it was not significant. There was a higher influx of neutrophils and a decrease of mononuclear population on the 7th day (p < 0.05). On the 14th day, these differences were observed only in the tadalafil group (p < 0.05). This study suggested positive results with the use of sildenafil and tadalafil as adjuvant drugs in skin flap viability.

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Preoperative subcutaneous sildenafil injection increases random flap survival in rats

Abstract: The subdermal high dose sildenafil has a positive effect on flap survival.

Cited by 10 publications

References 21 publications

The Effects of Sildenafil and/or Nitroglycerin on Random-pattern Skin Flaps After Nicotine Application in Rats

The Effects of Sildenafil and/or Nitroglycerin on Random-pattern Skin Flaps After Nicotine Application in Rats

Redo pelvic fracture urethral injury repair: The case for tadalafil

Effects of sildenafil and tadalafil on skin flap viability

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