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Facial Plast Surg 2014; 30(01): 084-090
DOI: 10.1055/s-0033-1363758
Rapid Communication
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Does Phosphodiesterase Inhibition Lessen Facial Flap Necrosis in Tobacco Cigarette Users?

Miles Pfaff
1   Section of Plastic Surgery, Yale University, New Haven, Connecticut
,
Ajul Shah
1   Section of Plastic Surgery, Yale University, New Haven, Connecticut
,
Derek Steinbacher
1   Section of Plastic Surgery, Yale University, New Haven, Connecticut
› Author Affiliations
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Publication History

Publication Date:
31 January 2014 (online)

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Abstract

Tobacco cigarette smoking remains a serious risk factor for necrosis of local facial skin flaps. To date, no pharmacological therapies exist for cigarette smoke-induced impairment of skin flap tissue survival. Accumulating evidence suggest that phosphodiesterase-5 (PDE-5) inhibitor therapy may counteract the negative effects of cigarette smoke on flap survival. Here, we evaluate skin flap survival in a series of consecutive tobacco cigarette users treated with the PDE-5 inhibitor, sildenafil, who underwent local flap facial reconstruction. We included 11 patients (5 females; median age: 64) with a significant smoking history. Seventeen facial flaps were performed for 14 defects. All patients received sildenafil in the postoperative setting. One complication of necrosis of the flap distal margin was encountered. Follow-up was available for all patients. Our results demonstrate that facial reconstruction in tobacco cigarette smokers can be performed with improved success and that sildenafil therapy may mitigate the deleterious effects of smoking on flap survival.

Keywords

phosphodiesterase-5 inhibitor - PDE-5 inhibitor - facial flap - local flap - flap necrosis - flap failure - tobacco - smoking - sildenafil
 

  • References

  • 1 Ridgway EB, Pribaz JJ. The reconstruction of male hair-bearing facial regions. Plast Reconstr Surg 2011; 127 (1) 131-141
    PubMedGoogle Scholar
  • 2 Rapstine ED, Knaus II WJ, Thornton JF. Simplifying cheek reconstruction: a review of over 400 cases. Plast Reconstr Surg 2012; 129 (6) 1291-1299
    CrossrefPubMedGoogle Scholar
  • 3 Kerrigan CL. Skin flap failure: pathophysiology. Plast Reconstr Surg 1983; 72 (6) 766-777
    CrossrefPubMedGoogle Scholar
  • 4 Chang DW, Reece GP, Wang B , et al. Effect of smoking on complications in patients undergoing free TRAM flap breast reconstruction. Plast Reconstr Surg 2000; 105 (7) 2374-2380
    CrossrefPubMedGoogle Scholar
  • 5 Goodwin SJ, McCarthy CM, Pusic AL , et al. Complications in smokers after postmastectomy tissue expander/implant breast reconstruction. Ann Plast Surg 2005; 55 (1) 16-19 , discussion 19–20
    CrossrefPubMedGoogle Scholar
  • 6 Padubidri AN, Yetman R, Browne E , et al. Complications of postmastectomy breast reconstructions in smokers, ex-smokers, and nonsmokers. Plast Reconstr Surg 2001; 107 (2) 342-349 , discussion 350–351
    CrossrefPubMedGoogle Scholar
  • 7 Kinsella JB, Rassekh CH, Wassmuth ZD, Hokanson JA, Calhoun KH. Smoking increases facial skin flap complications. Ann Otol Rhinol Laryngol 1999; 108 (2) 139-142
    CrossrefPubMedGoogle Scholar
  • 8 Rees TD, Liverett DM, Guy CL. The effect of cigarette smoking on skin-flap survival in the face lift patient. Plast Reconstr Surg 1984; 73 (6) 911-915
    CrossrefPubMedGoogle Scholar
  • 9 Mosely LH, Finseth F. Cigarette smoking: impairment of digital blood flow and wound healing in the hand. Hand 1977; 9 (2) 97-101
    PubMedGoogle Scholar
  • 10 Eckardt A, Fokas K. Microsurgical reconstruction in the head and neck region: an 18-year experience with 500 consecutive cases. J Craniomaxillofac Surg 2003; 31 (4) 197-201
    CrossrefPubMedGoogle Scholar
  • 11 Parikh SS, Jacono AA. Deep-plane face-lift as an alternative in the smoking patient. Arch Facial Plast Surg 2011; 13 (4) 283-285
    CrossrefPubMedGoogle Scholar
  • 12 Campanile G, Hautmann G, Lotti T. Cigarette smoking, wound healing, and face-lift. Clin Dermatol 1998; 16 (5) 575-578
    CrossrefPubMedGoogle Scholar
  • 13 Raij L, DeMaster EG, Jaimes EA. Cigarette smoke-induced endothelium dysfunction: role of superoxide anion. J Hypertens 2001; 19 (5) 891-897
    CrossrefPubMedGoogle Scholar
  • 14 Jaimes EA, DeMaster EG, Tian RX, Raij L. Stable compounds of cigarette smoke induce endothelial superoxide anion production via NADPH oxidase activation. Arterioscler Thromb Vasc Biol 2004; 24 (6) 1031-1036
    CrossrefPubMedGoogle Scholar
  • 15 Csiszar A, Podlutsky A, Wolin MS, Losonczy G, Pacher P, Ungvari Z. Oxidative stress and accelerated vascular aging: implications for cigarette smoking. Front Biosci (Landmark Ed) 2009; 14: 3128-3144
    PubMedGoogle Scholar
  • 16 Bivalacqua TJ, Sussan TE, Gebska MA , et al. Sildenafil inhibits superoxide formation and prevents endothelial dysfunction in a mouse model of secondhand smoke induced erectile dysfunction. J Urol 2009; 181 (2) 899-906
    CrossrefPubMedGoogle Scholar
  • 17 Senthilkumar A, Smith RD, Khitha J , et al. Sildenafil promotes ischemia-induced angiogenesis through a PKG-dependent pathway. Arterioscler Thromb Vasc Biol 2007; 27 (9) 1947-1954
    CrossrefPubMedGoogle Scholar
  • 18 Sahara M, Sata M, Morita T, Nakajima T, Hirata Y, Nagai R. A phosphodiesterase-5 inhibitor vardenafil enhances angiogenesis through a protein kinase G-dependent hypoxia-inducible factor-1/vascular endothelial growth factor pathway. Arterioscler Thromb Vasc Biol 2010; 30 (7) 1315-1324
    CrossrefPubMedGoogle Scholar
  • 19 Pyriochou A, Zhou Z, Koika V , et al. The phosphodiesterase 5 inhibitor sildenafil stimulates angiogenesis through a protein kinase G/MAPK pathway. J Cell Physiol 2007; 211 (1) 197-204
    CrossrefPubMedGoogle Scholar
  • 20 Taibi G, Carruba G, Miceli V, Cocciadiferro L, Cucchiara A, Nicotra CM. Sildenafil protects epithelial cell through the inhibition of xanthine oxidase and the impairment of ROS production. Free Radic Res 2010; 44 (2) 232-239
    CrossrefPubMedGoogle Scholar
  • 21 Koupparis AJ, Jeremy JY, Muzaffar S, Persad R, Shukla N. Sildenafil inhibits the formation of superoxide and the expression of gp47 NAD[P]H oxidase induced by the thromboxane A2 mimetic, U46619, in corpus cavernosal smooth muscle cells. BJU Int 2005; 96 (3) 423-427
    CrossrefPubMedGoogle Scholar
  • 22 Gur S, Sikka SC, Hellstrom WJ. Novel phosphodiesterase-5 (PDE5) inhibitors in the alleviation of erectile dysfunction due to diabetes and ageing-induced oxidative stress. Expert Opin Investig Drugs 2008; 17 (6) 855-864
    CrossrefPubMedGoogle Scholar
  • 23 Sarifakioglu N, Gokrem S, Ates L, Akbuga UB, Aslan G. The influence of sildenafil on random skin flap survival in rats: an experimental study. Br J Plast Surg 2004; 57 (8) 769-772
    CrossrefPubMedGoogle Scholar
  • 24 Hart K, Baur D, Hodam J , et al. Short- and long-term effects of sildenafil on skin flap survival in rats. Laryngoscope 2006; 116 (4) 522-528
    CrossrefPubMedGoogle Scholar
  • 25 Bandera BC, Pham T, Hill-Pryor C , et al. Role of growth factors in improved skin flap viability caused by phosphodiesterase-5 inhibitor. Am Surg 2010; 76 (6) 614-617
    PubMedGoogle Scholar
  • 26 Powell JT. Vascular damage from smoking: disease mechanisms at the arterial wall. Vasc Med 1998; 3 (1) 21-28
    CrossrefPubMedGoogle Scholar
  • 27 Aronow WS. Editorial: smoking, carbon monoxide, and coronary heart disease. Circulation 1973; 48 (6) 1169-1172
    CrossrefPubMedGoogle Scholar
  • 28 Leite MT, Gomes HC, Percário S, Russo CR, Ferreira LM. Dimethyl sulfoxide as a block to the deleterious effect of nicotine in a random skin flap in the rat. Plast Reconstr Surg 2007; 120 (7) 1819-1822
    PubMedGoogle Scholar
  • 29 Mosely LH, Finseth F, Goody M. Nicotine and its effect on wound healing. Plast Reconstr Surg 1978; 61 (4) 570-575
    CrossrefPubMedGoogle Scholar
  • 30 Black CE, Huang N, Neligan PC , et al. Effect of nicotine on vasoconstrictor and vasodilator responses in human skin vasculature. Am J Physiol Regul Integr Comp Physiol 2001; 281 (4) R1097-R1104
    PubMedGoogle Scholar
  • 31 Cardoso JF, Souza BR, Amadeu TP, Valença SS, Porto LC, Costa AM. Effects of cigarette smoke in mice wound healing is strain dependent. Toxicol Pathol 2007; 35 (7) 890-896
    CrossrefPubMedGoogle Scholar
  • 32 Talukder MA, Johnson WM, Varadharaj S , et al. Chronic cigarette smoking causes hypertension, increased oxidative stress, impaired NO bioavailability, endothelial dysfunction, and cardiac remodeling in mice. Am J Physiol Heart Circ Physiol 2011; 300 (1) H388-H396
    CrossrefPubMedGoogle Scholar
  • 33 Little SC, Hughley BB, Park SS. Complications with forehead flaps in nasal reconstruction. Laryngoscope 2009; 119 (6) 1093-1099
    CrossrefPubMedGoogle Scholar
  • 34 Paddack AC, Frank RW, Spencer HJ, Key JM, Vural E. Outcomes of paramedian forehead and nasolabial interpolation flaps in nasal reconstruction. Arch Otolaryngol Head Neck Surg 2012; 138 (4) 367-371
    CrossrefPubMedGoogle Scholar
  • 35 Riefkohl R, Wolfe JA, Cox EB, McCarty Jr KS. Association between cutaneous occlusive vascular disease, cigarette smoking, and skin slough after rhytidectomy. Plast Reconstr Surg 1986; 77 (4) 592-595
    CrossrefPubMedGoogle Scholar
  • 36 Dardour JC, Pugash E, Aziza R. The one-stage preauricular flap for male pattern baldness: long-term results and risk factors. Plast Reconstr Surg 1988; 81 (6) 907-912
    PubMedGoogle Scholar
  • 37 Davies BW, Lewis RD, Pennington G. The impact of vasodilators on random-pattern skin flap survival in the rat following mainstream smoke exposure. Ann Plast Surg 1998; 40 (6) 630-636
    CrossrefPubMedGoogle Scholar
  • 38 Aker JS, Mancoll J, Lewis B, Colen LB. The effect of pentoxifylline on random-pattern skin-flap necrosis induced by nicotine treatment in the rat. Plast Reconstr Surg 1997; 100 (1) 66-71
    PubMedGoogle Scholar
  • 39 Mauad Jr RJ, Shimizu MH, Mauad T, de Tolosa EM. Buflomedil and pentoxifylline in the viability of dorsal cutaneous flaps of rats treated with nicotine. J Plast Reconstr Aesthet Surg 2006; 59 (4) 387-392
    CrossrefPubMedGoogle Scholar
  • 40 Park JW, Mrowietz C, Chung N, Jung F. Sildenafil improves cutaneous microcirculation in patients with coronary artery disease: a monocentric, prospective, double-blind, placebo-controlled, randomized cross-over study. Clin Hemorheol Microcirc 2004; 31 (3) 173-183
    PubMedGoogle Scholar
  • 41 Shah A, Pfaff MJ, Wu W, Steinbacher DM. PDE-5 inhibition improves skin flap viability in rats that are exposed to nicotine. Plastic Surgery Research Council, Santa Monico, CA, May 2–4, 2013
    PubMedGoogle Scholar