Improved Flap Viability With Site-Specific Delivery of Sildenafil Citrate Using Fibrin Glue

Abstract

Sildenafil is a cyclic guanosine-specific phosphodiesterase type 5 (PD-5) inhibitor that is widely used for erectile dysfunction. Potent and competitive inhibition of PD-5 enhances levels of cyclic guanosine monophosphate (cGMP). Fibrin glue-apart from tissue fixation-has been used for slow release of drugs. In this study, local delivery of Sildenafil citrate with fibrin glue was accomplished to improve random flap survival. Fifty Wistar rats were randomized into 5 groups, and a standardized dorsal random-pattern skin flap was elevated in each rat. In Group I (n = 10), the base of the flap was divided, making it a "graft" control to study the graft effect. In Group II (n = 10), a thin Silastic sheet was used to separate the flap from the underlying vascular bed, and no pharmacologic treatment was given. In Group III (n = 10), only 0.5 mL of fibrin glue was applied to the flap donor site. In Group IV (n = 10), 2.5 mg of sildenafil citrate mixed in 0.5 mL of fibrin glue was applied to donor site of the flap, whereas 10 mg of sildenafil citrate mixed in 0.5 mL of fibrin glue was applied in Group V (n = 10). Area of flap survival was evaluated on postoperative seventh day. Total necrosis of all of the flaps was observed in "graft" control group (Group I). Sildenafil and fibrin glue groups (Group IV and V) resulted in a statistically significant decrease in flap necrosis compared with Groups II and III (P < 0.0001). A statistically significant difference could not be documented between Group II and Group III (P > 0.0001). The decrease in skin necrosis was statistically significant in Group V compared with Group IV (P < 0.0001). Histologic examination revealed significantly increased vascular density in Groups IV and V compared with Groups II and III (P < 0.0001), whereas a significant difference could not be documented between Groups IV and V (P > 0.0001) and between Groups II and III (P > 0.0001). In view of these results, topical sildenafil application seems to improve flap survival in random-pattern skin flaps in dose-dependent manner.

Phosphodiesterase inhibitors in vascular ischemia: A case report and review of their use in ischemic conditions

“…Using a rat dorsal random-pattern skin flap, administration of sildenafil in fibrin glue resulted in a significant decrease in flap necrosis, suggesting that topical sildenafil application improves flap survival in rat models (30). In a similar study (31), distally based dorsal skin flaps investigating sildenafil showed dose-dependent effects on random flap survival in rats, with higher doses and shorter intervals increasing efficacy.…”

Effects of Vardenafil on Testicular Torsion/Detorsion Damage: An Experimental Study in Pigs

“…Although the main indication of PDE-5 inhibitors is ED, the effectiveness of sildenafil in hypertensive cardiomyopathy [15] , pulmonary hypertension [16] , and renal damage via the NO pathway [17] has been reported previously. The favorable effects of PDE-5 usage on several tissues and organs, such as in flap survival and trans- planted and other organs, have been recently reported [18][19][20] . These new indications and the usage profile of these drugs led us to investigate their efficacy on I/R injury of the testis.…”

Effect of sildenafil citrate on secondary healing in full thickness skin defects in experiment

“…Omiderm accelerates the keratinocyte proliferation process by accumulating under the exsudate and thereby upregulating the epithelisation process as well as protecting the wound from being infected by the environment (16). Nitric oxide (NO) has been discovered in 1980's and it's effects on wound healing has been extensively studied over the past decades (29)(30)(31). NO is synthetized by many types of cells and acts in neurotransmission, regulating the immune system, vessel smooth muscle relaxation and decreasing platelet aggregation to name a few of the properties.…”