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

Abstract

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...

Comparative effect of administration and discontinuation of sildenafil and/or clomipramine on the hepatic, cardiac and testicular tissues of male rats

“…It is used for the treatment of angina and ED in males. Sildenafil is a specific inhibitor of type 5 cyclic guanosine monophosphate (cGMP)‐specific phosphodiesterases (PDE), the main isozyme that metabolises cGMP in the corpus cavernosum (Ayyildiz et al., 2007; Ellabban et al., 2020). It enhances the effects of nitric oxide (NO)‐mediated smooth muscle relaxation by suppressing cGMP degradation by PDE5, thereby promoting penile erection (Ramani & Park, 2010).…”

Pseudoginsenoside F11 Enhances the Viability of Random-Pattern Skin Flaps by Promoting TFEB Nuclear Translocation Through AMPK-mTOR Signal Pathway

“…Random-pattern skin flaps are commonly used in clinical practice to repair skin injury and cover wounds because of its high efficiency and convenience ( Yu et al, 2013 ; Park et al, 2015 ). However, several post-operative complications limit its clinical application, the most serious of which was the flap necrosis ( Ellabban et al, 2020 ). Lack of axial vasculature and insufficient oxygen supplement in the distal part of the flap are the main causes of necrosis ( Namazi, 2014 ; Chang et al, 2017 ).…”

The secretome of stressed peripheral blood mononuclear cells increases tissue survival in a rodent epigastric flap model

“…10 Experimental therapies including the use of antioxidants, vasodilators, anti-inflammatory drugs, and hyperbaric oxygen led to a decrease in necrosis rates. [11][12][13][14][15][16] Alternatively, therapeutic angiogenesis through the application of pro-angiogenic factors, such as Platelet-derived growth factor (PDGF), and Vascular Endothelial Growth Factor (VEGF) has been demonstrated to improve the survival of compromised flaps by improving tissue perfusion. 10,[17][18][19][20][21] The use of platelet-rich plasma (PRP) resulted in an increase in flap survival of 20% by inducing angiogenesis and reducing the inflammatory response.…”