PDE-5 inhibition improves skin flap viability in rats that are exposed to nicotine

Shah, Ajul; Pfaff, Miles J.; Assi, Roland; Wu, Wei; Steinbacher, Derek M.

doi:10.1002/micr.22237

Cited by 9 publications

(11 citation statements)

References 45 publications

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“…1). Mauad et al 18 , Eskitascioglu and Gunay 40 , and Shah et al 8 also reported that nicotine administration decreases random flap survival rate to a range between 77.7% and 50.4%. These different percentages may be due to the difference in flap size, nicotine doses used, site of nicotine injection or species of the rats, but in general nicotine showed a deleterious effect on skin flaps.…”

Section: Discussionmentioning

confidence: 97%

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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: 97%

“…Nicotine (Sigma Chemical, St Louis, MO, USA) was given at a dose of 4 mg/kg by daily SC injections in 1 ml normal saline for 40 days before surgery and 7 days after 18 . Nicotine was injected at the site of the base of the future flap 8 . SC injections were used for slower absorption rates to overcome the high toxicity of nicotine.…”

Section: Methodsmentioning

confidence: 99%

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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“…These observations are corroborated by preliminary laboratory results from our group demonstrating enhanced flap tissue survival after administration of sildenafil in the setting of nicotine exposure in a rodent flap model. 41 On the basis of these beneficial vascular and perfusion effects, we sought to investigate the role of PDE-5 inhibitor on a clinical series of tobacco cigarette smoker undergoing facial flap reconstruction with the hypothesis that PDE-5 inhibitors would reverse the damaged and suboptimal vascular environment present in a tobacco user's skin flap. Before administration of sildenafil, we paid critical attention to characteristics of robust flap design.…”

Section: Discussionmentioning

confidence: 99%

Does Phosphodiesterase Inhibition Lessen Facial Flap Necrosis in Tobacco Cigarette Users?

2014

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Tobacco cigarette smoking remains a serious risk factor for necrosis of local facial skin flaps. To date, no pharmacological therapies exist for cigarette smoke-induced impairment of skin flap tissue survival. Accumulating evidence suggest that phosphodiesterase-5 (PDE-5) inhibitor therapy may counteract the negative effects of cigarette smoke on flap survival. Here, we evaluate skin flap survival in a series of consecutive tobacco cigarette users treated with the PDE-5 inhibitor, sildenafil, who underwent local flap facial reconstruction. We included 11 patients (5 females; median age: 64) with a significant smoking history. Seventeen facial flaps were performed for 14 defects. All patients received sildenafil in the postoperative setting. One complication of necrosis of the flap distal margin was encountered. Follow-up was available for all patients. Our results demonstrate that facial reconstruction in tobacco cigarette smokers can be performed with improved success and that sildenafil therapy may mitigate the deleterious effects of smoking on flap survival.

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“…The drug inhibits PDE5, elevating the intracellular cGMP level, in turn increasing blood flow, triggering vasodilation, and inhibiting thrombus formation by virtue of an effect on platelets. Sildenafil has been used to increase the viable areas of randomly patterned flaps . Experimentally, sildenafil has been shown to protect against I/R injury .…”

Section: Discussionmentioning

confidence: 99%

“…Sildenafil has been used to increase the viable areas of randomly patterned flaps. 7,8,26 Experimentally, sildenafil has been shown to protect against I/R injury. 27 Gori et al 28 showed that sildenafil opens K ATP -sensitive channels, reducing I/R injury and endothelial dysfunction.…”

Section: Discussionmentioning

confidence: 99%

The effect of mesenchymal stem cells and sildenafil on flap viability in perforator‐based flaps for ischemia/reperfusion injury: An experimental study

et al. 2015

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In this rat pedicled perforator based abdominal flap, we found that after primary ischemia, application of MSCs and SC, either individually or in combined form, significantly enhanced antioxidant enzyme levels compared with those in the control group, and provided protection against ischemia/reperfusion injury. The two treatments acted synergistically to protect against damage after 4 hours of ischemia, but either treatment alone more effectively enhanced viable flap area after 8 hours of ischemia, although some flap damage was apparent. © 2015 Wiley Periodicals, Inc. Microsurgery 36:402-409, 2016.

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PDE-5 inhibition improves skin flap viability in rats that are exposed to nicotine

Abstract: PDE-5 inhibition exhibits a dose-dependent reduction in skin flap necrosis in rats exposed to nicotine. This suggests that PDE-5 inhibition may mitigate the ill effects of smoking on skin flaps.

Cited by 9 publications

References 45 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

Does Phosphodiesterase Inhibition Lessen Facial Flap Necrosis in Tobacco Cigarette Users?

The effect of mesenchymal stem cells and sildenafil on flap viability in perforator‐based flaps for ischemia/reperfusion injury: An experimental study

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