Eur J Pediatr Surg 2012; 22(06): 460-464
DOI: 10.1055/s-0032-1315808
Original Article
Georg Thieme Verlag KG Stuttgart · New York

Effect of VEGF on Angiogenesis in Pedicle Penile Skin Flaps: An Experimental Study of Urethral Reconstruction in Rabbits

Elefteria Efstathiou
1   Alexandroupolis University Hospital, Laboratory of Experimental Surgery and Surgical Research, Alexandroupolis, Greece
,
Stefanos Gardikis
2   Department of Pediatric Surgery, Alexandroupolis University Hospital, Alexandroupolis, Greece
,
Alexandra Giatromanolaki
3   Department of Pathology, Alexandroupolis University Hospital, Alexandroupolis, Germany
,
Katerina Kambouri
2   Department of Pediatric Surgery, Alexandroupolis University Hospital, Alexandroupolis, Greece
,
Efthimios Sivridis
3   Department of Pathology, Alexandroupolis University Hospital, Alexandroupolis, Germany
,
Constantinos Simopoulos
1   Alexandroupolis University Hospital, Laboratory of Experimental Surgery and Surgical Research, Alexandroupolis, Greece
,
George Vaos
2   Department of Pediatric Surgery, Alexandroupolis University Hospital, Alexandroupolis, Greece
› Author Affiliations
Further Information

Publication History

12 February 2012

21 April 2012

Publication Date:
10 July 2012 (online)

Abstract

Introduction The aim of this study was to investigate the expression of vascular endothelial growth factor (VEGF) in pedicle penile skin flaps (PPSFs) used for urethral reconstruction in rabbits and the effect of exogenous VEGF on the angiogenesis process in the PPSFs.

Methods We randomly divided 28 male New Zealand rabbits into two sets of animals. A ventral urethral defect was created in all animals. In the first set of animals (first experiment, n = 10), a PPSF was used for the repair and VEGF expression in the flap was estimated on days 1, 2, 3, 5, and 7 postoperatively. The second set of animals (second experiment, n = 18) included three groups: control, untreated, and VEGF groups. In control group (n = 6), the defect was repaired by simple closure. In untreated (n = 6) and VEGF (n = 6) groups, a PPSF was used for the reconstruction. In VEGF group, exogenous VEGF was injected subdermally on the postoperative day corresponding to the peak endogenous VEGF expression (first experiment results). The animals were sacrificed on the 21st postoperative day and the angiogenic activity was assessed. A p < 0.05 was considered statistically significant.

Results The highest expression of endogenous VEGF in PPSFs was noted on postoperative day 3. Angiogenesis in control, untreated, and VEGF groups was 23.06 ± 4.1, 30.00 ± 6.9, and 34.7 ± 6.9 (mean values ± standard deviation) vessels per optical field, respectively. There were statistically significant differences between control–untreated groups (p = 0.04) and untreated–VEGF groups (p < 0.0001), and indicative difference between untreated and VEGF groups (p = 0.064).

Conclusions VEGF is expressed in PPSFs, used for urethral reconstruction in rabbits. Flap angiogenesis is much higher than angiogenesis in simple wound closure. VEGF injection on postoperative day 3 seems to enhance angiogenesis in flaps.

 
  • References

  • 1 Baskin LS. Hypospadias. In: Grosfeld JL, O'Neill JA, Coran AG, Fonkalsrud EW, eds. Pediatric Surgery. 6th ed. Philadelphia: Mosby; 2006: 1870-1898
  • 2 Snodgrass WT. Hypospadias urethroplasty. In: Wilcox DT, Godbole PP, Koyle MA, , eds. Pediatric Urology: Surgical Complications and Management. 1st ed. West Sussex: Wiley-Blackwell; 2008: 201-211
  • 3 Daniel RK, Kerrigan CL. Principles and physiology of skin flap surgery. In: McCarthy JG, ed. Plastic Surgery, 3rd ed. Philadelphia: Saunders; 1990: 275-328
  • 4 Marti HH, Risau W. Angiogenesis in ischemic disease. Thromb Haemost 1999; 82 (Suppl. 01) 44-52
  • 5 Ferrara N, Gerber HP, LeCouter J. The biology of VEGF and its receptors. Nat Med 2003; 9 (6) 669-676
  • 6 Zachary I. Vascular endothelial growth factor. Int J Biochem Cell Biol 1998; 30 (11) 1169-1174
  • 7 Chodak GW, Thisted RA, Gerber GS , et al. Results of conservative management of clinically localized prostate cancer. N Engl J Med 1994; 330 (4) 242-248
  • 8 Yang R, Thomas GR, Bunting S , et al. Effects of vascular endothelial growth factor on hemodynamics and cardiac performance. J Cardiovasc Pharmacol 1996; 27 (6) 838-844
  • 9 Alon T, Hemo I, Itin A, Pe'er J, Stone J, Keshet E. Vascular endothelial growth factor acts as a survival factor for newly formed retinal vessels and has implications for retinopathy of prematurity. Nat Med 1995; 1 (10) 1024-1028
  • 10 Risau W. Mechanisms of angiogenesis. Nature 1997; 386 (6626) 671-674
  • 11 Tonnesen MG, Feng X, Clark RA. Angiogenesis in wound healing. J Investig Dermatol Symp Proc 2000; 5 (1) 40-46
  • 12 Shweiki D, Itin A, Soffer D, Keshet E. Vascular endothelial growth factor induced by hypoxia may mediate hypoxia-initiated angiogenesis. Nature 1992; 359 (6398) 843-845
  • 13 Liu Y, Cox SR, Morita T, Kourembanas S. Hypoxia regulates vascular endothelial growth factor gene expression in endothelial cells. Identification of a 5′ enhancer. Circ Res 1995; 77 (3) 638-643
  • 14 Gardikis S, Giatromanolaki A, Ypsilantis P , et al. Comparison of angiogenic activities after urethral reconstruction using free grafts in rabbits. Eur Urol 2005; 47 (3) 417-421
  • 15 Kambouri K, Gardikis S, Giatromanolaki A , et al. Comparison of angiogenic activity after urethral reconstruction using free grafts and pedicle flap: an experimental study. Eur J Pediatr Surg 2006; 16 (5) 323-328
  • 16 Lineaweaver WC, Lei MP, Mustain W, Oswald TM, Cui D, Zhang F. Vascular endothelium growth factor, surgical delay, and skin flap survival. Ann Surg 2004; 239 (6) 866-873 , discussion 873–875
  • 17 Wagatsuma A. Endogenous expression of angiogenesis-related factors in response to muscle injury. Mol Cell Biochem 2007; 298 (1-2) 151-159
  • 18 Zhang F, Oswald T, Lin S , et al. Vascular endothelial growth factor (VEGF) expression and the effect of exogenous VEGF on survival of a random flap in the rat. Br J Plast Surg 2003; 56 (7) 653-659
  • 19 Lindenblatt N, Calcagni M, Contaldo C, Menger MD, Giovanoli P, Vollmar B. A new model for studying the revascularization of skin grafts in vivo: the role of angiogenesis. Plast Reconstr Surg 2008; 122 (6) 1669-1680
  • 20 Takeshita S, Zheng LP, Brogi E , et al. Therapeutic angiogenesis. A single intraarterial bolus of vascular endothelial growth factor augments revascularization in a rabbit ischemic hind limb model. J Clin Invest 1994; 93 (2) 662-670
  • 21 Zhang ZG, Zhang L, Jiang Q , et al. VEGF enhances angiogenesis and promotes blood-brain barrier leakage in the ischemic brain. J Clin Invest 2000; 106 (7) 829-838
  • 22 Guzman MJ, Crisostomo PR, Wang M, Markel TA, Wang Y, Meldrum DR. Vascular endothelial growth factor improves myocardial functional recovery following ischemia/reperfusion injury. J Surg Res 2008; 150 (2) 286-292
  • 23 Yoshikawa T, Tohyama H, Katsura T , et al. Effects of local administration of vascular endothelial growth factor on mechanical characteristics of the semitendinosus tendon graft after anterior cruciate ligament reconstruction in sheep. Am J Sports Med 2006; 34 (12) 1918-1925
  • 24 Seipelt RG, Backer CL, Mavroudis C , et al. Topical VEGF enhances healing of thoracic aortic anastomosis for coarctation in a rabbit model. Circulation 2003; 108 Suppl (1) II150-II154
  • 25 Ishii M, Tanaka E, Imaizumi T , et al. Local VEGF administration enhances healing of colonic anastomoses in a rabbit model. Eur Surg Res 2009; 42 (4) 249-257
  • 26 Zhang F, Lei MP, Oswald TM , et al. The effect of vascular endothelial growth factor on the healing of ischaemic skin wounds. Br J Plast Surg 2003; 56 (4) 334-341
  • 27 Galiano RD, Tepper OM, Pelo CR , et al. Topical vascular endothelial growth factor accelerates diabetic wound healing through increased angiogenesis and by mobilizing and recruiting bone marrow-derived cells. Am J Pathol 2004; 164 (6) 1935-1947
  • 28 Kryger Z, Zhang F, Dogan T, Cheng C, Lineaweaver WC, Buncke HJ. The effects of VEGF on survival of a random flap in the rat: examination of various routes of administration. Br J Plast Surg 2000; 53 (3) 234-239
  • 29 Vourtsis SA, Spyriounis PK, Agrogiannis GD, Ionac M, Papalois AE. VEGF application on rat skin flap survival. J Invest Surg 2012; 25 (1) 14-19
  • 30 Simons M. Angiogenesis: where do we stand now?. Circulation 2005; 111 (12) 1556-1566