Short- and long-term effects of sildenafil on skin flap survival in rats.
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Department of Oral and Maxillofacial Surgery, Dwight David Eisenhower Army Medical Center, Fort Gordon, Georgia 30905, USA.
Kristopher
K
Hart
Dale
D
Baur
Jason
J
Hodam
Leslie
L
Lesoon-Wood
Mary
M
Parham
Karen
K
Keith
Raymond
R
Vazquez
Edward
E
Ager
Jose
J
Pizarro
D015106:3',5'-Cyclic-GMP Phosphodiesterases / Q000037:antagonists & inhibitors; D000818:Animals; D001783:Blood Flow Velocity / Q000187:drug effects; D062109:Dermatologic Surgical Procedures; D004195:Disease Models, Animal; D005500:Follow-Up Studies; D008297:Male; D008833:Microcirculation / Q000187:drug effects*; D009336:Necrosis / Q000473:pathology / Q000517:prevention & control; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology*; D011687:Purines; D051381:Rats; D017207:Rats, Sprague-Dawley; D000068677:Sildenafil Citrate; D013450:Sulfones; D013524:Surgical Flaps / Q000098:blood supply* / Q000473:pathology; D013997:Time Factors; D016896:Treatment Outcome
D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D000068677:Sildenafil Citrate; D015106:3',5'-Cyclic-GMP Phosphodiesterases