Effects of sildenafil and tadalafil on skin flap viability

Abstract

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.

Use of Phosphodiesterase Inhibitors in the Postoperative Period of Skin Flaps: A Systematic Review

“…1 The dose of sildenafil or tadalafil used in most studies was 5 mg/kg daily. 2,11 There are studies that applied tadalafil 10 mg/d in a single daily dose on the day of the procedure and on the next two subsequent days, resulting in three doses in total, and were successful in reducing flap necrosis rates. 3 On the other hand, another study with groups comparing 10 mg/kg of sildenafil, 10 mg/kg of tadalafil, and 10 mg/kg of vardenafil, administered 2 days before and 2 days after flap surgery, showed that although there were rates of minor necrosis compared with the control group, there was no statistically significant difference (P = 0.077).…”

“…12 Some studies on the use of medications may even improve flap circulation in smokers. 11,13 By administering PDE-V inhibition twice daily, animals exposed to nicotine show a reduction of more than 50% in skin flap necrosis when compared with the nicotine control group, in a statistically significant way. 10 Even with the dosage of 5 mg/d of tadalafil for 3 postoperative days, with the first dose after the procedure, a protective effect of flap necrosis was observed in smokers.…”

“…8 U-74389G is a chemical compound of the lazaroid class, and they are synthetic aminoacids, without glucocorticoid and mineralocorticoid activity, exerting a lipid membrane with peroxidation action and functioning as oxygen-free radical protectors. 8 Regarding the time of use of these drugs for the potential effect of flap optimization, vascularization was observed, with evidence of a single dose in the postoperative period, 10 treatment for 3 days, 11 and studies highlighting the importance of using them for 7 days after performing the procedure. 12 Some studies on the use of medications may even improve flap circulation in smokers.…”

The efficacy of PDE5 inhibitors in diabetic patients

“…The effect was more pronounced in non-diabetic rats PDE5i-treated group demonstrated increased regional blood flow in the sciatic nerve tissue, improved motor and sensory conduction velocities and peripheral thermal sensitivity effects on microcirculation through reduced local degradation of NO. Some preclinical studies evaluated the effects of commonly used PDE5i's on the survival of skin flaps, including vascularisation, decrease in wound size and necrosis, yielding conflicting results [85][86][87] (see Table 1).…”

“… 83 , 84 Therefore, there has been an increased interest in the role of PDE5i in wound healing given their indirect dilatory effects on microcirculation through reduced local degradation of NO. Some preclinical studies evaluated the effects of commonly used PDE5i's on the survival of skin flaps, including vascularisation, decrease in wound size and necrosis, yielding conflicting results 85 , 86 , 87 (see Table 1 ).…”