Plastic Surgery Research Council
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PDE-5 INHIBITION IMPROVES SKIN FLAP VIABILITY IN RATS THAT ARE EXPOSED TO NICOTINE
Presenter: Ajul Shah, MD
Co-Authors: Pfaff M; Wu W; Steinbacher D
Yale University

Introduction: Smoking is a significant risk factor for skin flap necrosis. To date, no pharmacologic therapies exist to mitigate the negative effect of nicotine on skin flap perfusion and survival. Phosphodiesterase-5 inhibitors are shown to promote vessel dilation and be pro-angiogenic. The purpose of this study is to assess the effect of PDE-5 inhibition on skin flap survival in rats exposed to nicotine. We hypothesize that when animals exposed to nicotine are treated with PDE-5 inhibitors, the rate of skin flap necrosis will be decreased.

Materials and Methods: This study was approved by Yale University IACUC #2011-11427. A total of 50 male rats,12 weeks old, were studied. Groups were treated for 28 days pre-operatively with either 1) normal saline control 2) nicotine only 3) sildenafil only 4) nicotine + sildenafil BID. Modified McFarlane flaps were then created (measuring 3 x 7 cm), silicone sheets were interposed between the flap and wound bed, and the flaps sutured back into place. Photographs were taken at 1, 3, and 7 days post-operatively. On day 7, rats were euthanized and flaps were harvested. VEG-F Western Blot analysis and histologic vessel density was measured.

Results: ImageJ software was used for analysis. Necrotic index (necrotic area divided by total flap area) was measured at post-operative day 1,3, and 7. Average NI for saline control group was .101 and .162 for post operative day 3 and 7 respectively. Nicotine only - .0928 and .1770. Sildenafil QD only - .0711 and .1630. Sildenafil BID and nicotine - .0726 and .107. Twice daily dosing of Sildenafil demonstrated a 40% reduction in necrosis of skin flaps exposed to nicotine. These results were statistically significant (p = 0.035).

Conclusion: This study demonstrates that PDE-5 inhibition exhibits a dose dependent improvement in the skin flap viability of rats exposed to nicotine. Our research suggests that PDE-5 Inhibition is protective against the potential detriments of smoking on skin flaps.


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