J Reconstr Microsurg 2016; 32(09): 643-649
DOI: 10.1055/s-0036-1584808
Original Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

The Effect of Inducible Nitric Oxide Synthase on Multiterritory Perforator Flap Survival in Rats

Xian-Yao Tao
1   Department of Hand and Plastic Surgery, The Second Affiliated Hospital of Wenzhou Medical University, The Second Clinical Medical College of Wenzhou Medical University, Wenzhou, China
,
Long Wang
1   Department of Hand and Plastic Surgery, The Second Affiliated Hospital of Wenzhou Medical University, The Second Clinical Medical College of Wenzhou Medical University, Wenzhou, China
,
Wei-Yang Gao
1   Department of Hand and Plastic Surgery, The Second Affiliated Hospital of Wenzhou Medical University, The Second Clinical Medical College of Wenzhou Medical University, Wenzhou, China
,
Jian Ding
1   Department of Hand and Plastic Surgery, The Second Affiliated Hospital of Wenzhou Medical University, The Second Clinical Medical College of Wenzhou Medical University, Wenzhou, China
,
Xiao-Liang Feng
1   Department of Hand and Plastic Surgery, The Second Affiliated Hospital of Wenzhou Medical University, The Second Clinical Medical College of Wenzhou Medical University, Wenzhou, China
,
Zong-Wei Zhou
1   Department of Hand and Plastic Surgery, The Second Affiliated Hospital of Wenzhou Medical University, The Second Clinical Medical College of Wenzhou Medical University, Wenzhou, China
,
Liang-Hui Yang
1   Department of Hand and Plastic Surgery, The Second Affiliated Hospital of Wenzhou Medical University, The Second Clinical Medical College of Wenzhou Medical University, Wenzhou, China
› Author Affiliations
Further Information

Publication History

13 December 2015

20 May 2016

Publication Date:
01 July 2016 (online)

Abstract

Background Inducible nitric oxide synthase (iNOS) plays an important role in vasodilation, angiogenesis, and ischemia–reperfusion injury. We investigated the effects of iNOS on the survival and choke vessels of multiterritory perforator flaps in rats.

Methods In this study, 84 rats were divided into two groups of 42 rats each and subjected to multiterritory perforator flap operations. Rats in group A received daily intraperitoneal doses of 100 mg per kg of aminoguanidine (AG) and rats in group B received daily intraperitoneal injections of the same volume of saline solution. On postoperative day 7, the surviving flap area was calculated as a percentage of the total flap dimensions using DP2-BSW software. The diameter and density of microvessels in the second choke zone of the flap were calculated from histology studies. The nitric oxide (NO) content was measured using NO concentration assay kits, and the levels of vascular endothelial growth factor (VEGF) and iNOS were assessed using western blotting. Superoxide dismutase (SOD) activity and malondialdehyde (MDA) content were measured using test kits. Laser Doppler imaging was used to evaluate flap perfusion in the second choke zone for 7 days after surgery.

Results The flap survival area, diameter and density of microvessels, iNOS and VEGF levels, NO content, blood perfusion, and MDA content were significantly higher in the control group compared with the AG group, whereas SOD activity was significantly lower in the control group.

Conclusions iNOS has a beneficial effect on the survival of multiterritory perforator flaps.

 
  • References

  • 1 Miyamoto S, Minabe T, Harii K. Effect of recipient arterial blood inflow on free flap survival area. Plast Reconstr Surg 2008; 121 (2) 505-513
  • 2 Gao ZM, Lin DM, Wang Y, Li JJ, Chen S, Gao WY. Role of the NO/cGMP pathway in postoperative vasodilation in perforator flaps. J Reconstr Microsurg 2015; 31 (2) 107-112
  • 3 Wang Y, Chen SY, Gao WY , et al. Experimental study of survival of pedicled perforator flap with flow-through and flow-end blood supply. Br J Surg 2015; 102 (4) 375-381
  • 4 Zhuang Y, Hu S, Wu D, Tang M, Xu C. A novel in vivo technique for observations of choke vessels in a rat skin flap model. Plast Reconstr Surg 2012; 130 (2) 308-317
  • 5 Cormack GC, Lamberty BG. A classification of fascio-cutaneous flaps according to their patterns of vascularisation. Br J Plast Surg 1984; 37 (1) 80-87
  • 6 Williams BA, Currie RW, Morris SF. Impact of arteriogenesis in plastic surgery: choke vessel growth proceeds via arteriogenic mechanisms in the rat dorsal island skin flap. Microcirculation 2009; 16 (3) 235-250
  • 7 El-Sabbagh AH. Skin perforator flaps: an algorithm for leg reconstruction. J Reconstr Microsurg 2011; 27 (9) 511-523
  • 8 Taylor GI, Palmer JH. The vascular territories (angiosomes) of the body: experimental study and clinical applications. Br J Plast Surg 1987; 40 (2) 113-141
  • 9 McDonald WS, Lo Jr TP, Thurmond M , et al. Role of nitric oxide in skin flap delay. Plast Reconstr Surg 2004; 113 (3) 927-931
  • 10 Gribbe O, Samuelson UE, Wiklund NP. Effects of nitric oxide synthase inhibition on blood flow and survival in experimental skin flaps. J Plast Reconstr Aesthet Surg 2007; 60 (3) 287-293
  • 11 Rozen WM, Whitaker IS, Ashton MW, Grinsell D. Changes in vascular anatomy following reconstructive surgery: an in vivo angiographic demonstration of the delay phenomenon and venous recanalization. J Reconstr Microsurg 2012; 28 (6) 363-365
  • 12 Dawson DA. Nitric oxide and focal cerebral ischemia: multiplicity of actions and diverse outcome. Cerebrovasc Brain Metab Rev 1994; 6 (4) 299-324
  • 13 Kane AJ, Barker JE, Mitchell GM , et al. Inducible nitric oxide synthase (iNOS) activity promotes ischaemic skin flap survival. Br J Pharmacol 2001; 132 (8) 1631-1638
  • 14 Zhang F, Oswald T, Holt J, Gerzenshtein J, Lei MP, Lineaweaver WC. Regulation of inducible nitric oxide synthase in ischemic preconditioning of muscle flap in a rat model. Ann Plast Surg 2004; 52 (6) 609-613
  • 15 Ozturk A, Fırat C, Parlakpınar H, Bay-Karabulut A, Kirimlioglu H, Gurlek A. Beneficial effects of aminoguanidine on skin flap survival in diabetic rats. Exp Diabetes Res 2012; 2012: 721256
  • 16 Ren H, Lin D, Mou Z, Dong P. The adverse effect of selective cyclooxygenase-2 inhibitor on random skin flap survival in rats. PLoS ONE 2013; 8 (12) e82802
  • 17 Ozkan F, Senayli Y, Ozyurt H, Erkorkmaz U, Bostan B. Antioxidant effects of propofol on tourniquet-induced ischemia-reperfusion injury: an experimental study. J Surg Res 2012; 176 (2) 601-607
  • 18 Yuan GJ, Zhou XR, Gong ZJ, Zhang P, Sun XM, Zheng SH. Expression and activity of inducible nitric oxide synthase and endothelial nitric oxide synthase correlate with ethanol-induced liver injury. World J Gastroenterol 2006; 12 (15) 2375-2381
  • 19 Tarpey MM, Wink DA, Grisham MB. Methods for detection of reactive metabolites of oxygen and nitrogen: in vitro and in vivo considerations. Am J Physiol Regul Integr Comp Physiol 2004; 286 (3) R431-R444
  • 20 Ogawa R, Oki K, Hyakusoku H. Skin perforator freeways and pathways: understanding the role of true and choke anastomoses between perforator angiosomes and their impact on skin flap planning and outcomes. Plast Reconstr Surg 2014; 133 (5) 719e-720e
  • 21 Callegari PR, Taylor GI, Caddy CM, Minabe T. An anatomic review of the delay phenomenon: I. Experimental studies. Plast Reconstr Surg 1992; 89 (3) 397-407 , discussion 417–418
  • 22 Gigliofiorito P, Iacob S, Pendolino AL, Piombino L, Segreto F, Persichetti P. True and “choke” anastomoses between perforator angiosomes: part I. Anatomical location. Plast Reconstr Surg 2014; 133 (6) 890e-891e
  • 23 Taylor GI, Corlett RJ, Dhar SC, Ashton MW. The anatomical (angiosome) and clinical territories of cutaneous perforating arteries: development of the concept and designing safe flaps. Plast Reconstr Surg 2011; 127 (4) 1447-1459
  • 24 Jia YC, Chen HH, Kang QL, Chai YM. Stimulation of nitric oxide production contributes to the antithrombotic effect of stromal cell-derived factor-1α in preventing microsurgical anastomotic thrombosis. J Reconstr Microsurg 2016;
  • 25 Ignarro LJ. Endothelium-derived nitric oxide: actions and properties. FASEB J 1989; 3 (1) 31-36
  • 26 Lineaweaver WC, Zhang F. Effects of CB-VEGF-A injection in rat flap models for improved survival. Plast Reconstr Surg 2014; 133 (3) 423e-424e
  • 27 Fang T, Lineaweaver WC, Chen MB, Kisner C, Zhang F. Effects of vascular endothelial growth factor on survival of surgical flaps: a review of experimental studies. J Reconstr Microsurg 2014; 30 (1) 1-13
  • 28 Fichter AM, Borgmann A, Ritschl LM , et al. Perforator flaps—how many perforators are necessary to keep a flap alive?. Br J Oral Maxillofac Surg 2014; 52 (5) 432-437
  • 29 Gözü A, Poda M, Taşkin EI , et al. Pretreatment with octreotide modulates iNOS gene expression, mimics surgical delay, and improves flap survival. Ann Plast Surg 2010; 65 (2) 245-249
  • 30 Taleb S, Moghaddas P, Rahimi Balaei M , et al. Metformin improves skin flap survival through nitric oxide system. J Surg Res 2014; 192 (2) 686-691
  • 31 Kelahmetoglu O, Demir R, Okten G, Demir A, Alpaslan Pinarli F, Diraman E. The effect of mesenchymal stem cells and sildenafil on flap viability in perforator-based flaps for ischemia/reperfusion injury: an experimental study. Microsurgery 2015; (e-pub ahead of print). doi: 10.1002/micr.22396
  • 32 Schmucker RW, Mendenhall SD, Reichensperger JD, Yang M, Neumeister MW. Defining the salvage time window for the use of ischemic postconditioning in skeletal muscle ischemia reperfusion injury. J Reconstr Microsurg 2015; 31 (8) 597-606
  • 33 Yazici S, Karahan O, Oral MK , et al. Comparison of renoprotective effect of dabigatran with low-molecular-weight heparin. Clin Appl Thromb Hemost 2016; 22 (4) 361-365
  • 34 Topp SG, Zhang F, Chatterjee T, Lineaweaver WC. Role of nitric oxide in surgical flap survival. J Am Coll Surg 2005; 201 (4) 628-639