Short- and Long-Term Effects of Sildenafil on Skin Flap Survival in Rats

Abstract

Distal ischemic necrosis of the flap remains an unsolved, challenging problem. Phosphodiesterase (PDE) inhibitors, which include the drug sildenafil, are a relatively new class of U.S. Food and Drug Administration-approved medications whose effect on tissue viability has not been widely explored. The vasodilatory effects of these drugs have the potential to enhance blood flow to flaps and increase their survivability. The purpose of this study was to examine the short- and long-term effects of sildenafil, administered intraperitoneally at a dose of 9 mg/kg per day, on the survival of surgical skin flaps in rats. A McFarlane-type random pattern skin (3 x 10-cm) flap model was used to evaluate the effect of sildenafil on necrosis at multiple time points. Rats were assigned to sildenafil-treated (9 mg/kg per day intraperitoneally; n = 34), vehicle control (n = 35), or sham (no injection; n = 40) groups. In each group, caudally based, dorsal, rectangular (3 x 10-cm) flaps were created. Flap necrosis was determined using orthogonal polarization spectral imaging and digital photography analysis on days 1, 3, 5, and 7 postsurgery. Orthogonal polarization spectral imaging results showed a significant decrease in necrosis and stasis in rats treated with sildenafil on days 1 and 3. Although reductions observed at days 5 and 7 were not as dramatic as days 1 and 3, digital photography analysis confirmed a decrease in the area of necrosis at all time points evaluated. These results suggest that PDE 5 inhibitors may play a more important role in early postoperative skin flap viability rather than at later time points and may be beneficial for skin flap viability as shown in the rat model. PDE 5 inhibitors may reduce the extent of necrosis after reconstructive surgeries.