J Reconstr Microsurg 2005; 21(8): 517-524
DOI: 10.1055/s-2005-922429
Copyright © 2005 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA.

Significant Angiogenic Potential is Present in the Microenvironment of Muscle Flaps in Humans

Peter M. Vogt1 , Pejman Boorboor1 , Bernhard Vaske2 , Ethem Topsakal1 , Marion Schneider3 , Thomas Muehlberger1
  • 1Department of Plastic and Reconstructive Surgery, Hannover Medical School, Hannover
  • 2Department of Biostatistics, Hannover Medical School, Hannover
  • 3Department of Experimental Anesthesiology, University Hospital Ulm, Ulm, Germany
Further Information

Publication History

Accepted: July 12, 2005

Publication Date:
17 November 2005 (online)

ABSTRACT

The purpose of this study was to determine the presence of growth factors and the quality of angiogenic potential in the wound microenvironment in different types of flaps in humans. The wound exudates from 23 flaps were processed for analysis of transforming growth factor β1 (TGF-β1), epidermal growth factor (EGF), interleukin 1α (IL-1α), platelet-derived growth factor-AB (PDGF-AB), vascular endothelial growth factor (VEGF), and insulin-like growth factor (IGF-1) by enzyme-linked immunosorbent assay (ELISA) or radio immuno assay (RIA). Angiogenic activity of wound fluid from latissimus flaps was determined by thymidine incorporation in porcine microendothelial cells exposed to various concentrations of wound fluid and control media. Angiogenic and matrix growth factors were altered in a linear fashion during the wound-healing process. Regression analysis provided evidence for decreasing levels of PDGF and EGF for latissimus flaps. Also, statistically significant differences of growth factor levels were found for paired comparison of flap types at different times after operation. Growth of in-vitro endothelial cells was stimulated most by 10 percent wound fluid, compared to any of the individual recombinant angiogenic factors or combinations of these factors. The data suggest that vascularized tissue flaps will promote wound healing by providing sufficient sources of growth factors in the wound environment. The particular type of flap, i.e., muscle or fasciocutaneous flap, does not seem to have an impact on growth-factor expression.

REFERENCES

  • 1 Anthony J P, Mathes S J, Alpert B S. The muscle flap in the treatment of chronic lower extremity osteomyelitis: results in patients over 5 years after treatment.  Plast Reconstr Surg. 1991;  88 311-318
  • 2 Keyser J E. Diabetic wound healing and limb salvage in an outpatient wound care program.  South Med J. 1993;  86 311-317
  • 3 Chang N, Mathes S J. Comparison of the effect of bacterial inoculation in musculocutaneous and random-patterned flaps.  Plast Reconstr Surg. 1982;  70 1-10
  • 4 Vogt P M, Lehnhardt M, Wagner D, Jansen V, Krieg M, Steinau H U. Determination of endogenous growth factors in human wound fluid-temporal presence and profiles of secretion.  Plast Reconstr Surg. 1998;  102 117-123
  • 5 Nahai F, Mathes S J. Musculocutaneous flap or muscle flap and skin graft?.  Ann Plast Surg. 1984;  12 199-203
  • 6 Mathes S J, Alpert B S, Chang N. Use of the muscle flap in chronic osteomyelitis: experimental and clinical correlation.  Plast Reconstr Surg. 1982;  69 815-829
  • 7 Mathes S J, Feng L J, Hunt T K. Coverage of the infected wound.  Ann Surg. 1983;  198 420-429
  • 8 Mathes S J. Chest wall reconstruction.  Clin Plast Surg. 1995;  22 187-198
  • 9 Calderon W, Chang N, Mathes S J. Comparison of the effect of bacterial inoculation in musculocutaneous and fasciocutaneous flaps.  Plast Reconstr Surg. 1986;  77 985-994
  • 10 Eshima I, Mathes S J, Paty P. Comparison of the intracellular bacterial killing activity of leukocytes in musculocutaneous and random-pattern flaps.  Plast Reconstr Surg. 1990;  86 541-547
  • 11 Feng L J, Price D C, Mathes S J, Hohn D. Dynamic properties of blood flow and leukocyte mobilization in infected flaps.  World J Surg. 1990;  14 796-803
  • 12 Gottrup F, Oredsson S, Price D C, Mathes S J, Hohn D. A comparative study of skin blood flow in musculocutaneous and random pattern flaps.  J Surg Res. 1984;  37 443-447
  • 13 Gottrup F, Firmin R, Hunt T K, Mathes S J. The dynamic properties of tissue oxygen in healing flaps.  Surgery. 1984;  95 527-536
  • 14 Gottrup F. Physiology and measurement of tissue perfusion.  Ann Chir Gynaecol. 1994;  83 183-189
  • 15 Greenhalgh D G. The role of growth factors in wound healing.  J Trauma. 1996;  41 159-167
  • 16 Beck L S, DeGuzmann L, Lee W P, Xu Y, Siegel M W, Amento E P. One systemic administration of transforming growth factor-beta 1 reverses age- or glucocorticoid impaired wound healing.  J Clin Invest. 1993;  92 2841-2849
  • 17 Senger D R, Brown L F, Claffey K P, Dvorak H F. Vascular permeability factor, tumor angiogenesis and stroma generation.  Invasion Metastasis. 1994;  14 385-394
  • 18 Howdieshell T R, Riegner C, Gupta V et al.. Normoxic wound fluid contains high levels of vascular endothelial growth factor.  Ann Surg. 1998;  228 707-715
  • 19 Battegay E J. Angiogenesis: mechanistic insights, neovascular diseases, and therapeutic prospects.  J Mol Med. 1995;  73 333-346
  • 20 Constant J S, Feng J J, Zabel D D et al.. Lactate elicits vascular endothelial growth factor from macrophages: a possible alternative to hypoxia.  Wound Rep Reg. 2000;  8 353-360
  • 21 Sheikh A Y, Gibson J J, Rollins M D et al.. Effect of hyperoxia on vascular endothelial growth factor levels in a wound model.  Arch Surg. 2000;  135 1293-1297
  • 22 Lewis J S, Landers R J, Underwood J C, Harris A L, Lewis C E. Expression of vascular endothelial growth factor by macrophages is up-regulated in poorly vascularized areas of breast carcinomas.  J Pathol. 2000;  192 150-158
  • 23 Unemori E N, Lewis M, Constant J et al.. Relaxin induces vascular endothelial growth factor expression and angiogenesis selectively at wound sites.  Wound Rep Reg. 2000;  8 361-370
  • 24 Nissen N N, Polverini P J, Koch A E, Volin M V, Gamelli R L, DiPietro L A. Vascular endothelial growth factor mediates angiogenic activity during the proliferative phase of wound healing.  Am J Pathol. 1998;  152 1445-1452
  • 25 Bennett N T, Schultz G S. Growth factors and wound healing: Part II. Role in normal and chronic wound healing.  Am J Surg. 1993;  166 74-81
  • 26 Allen D B, Maguire J J, Mahdavian M et al.. Wound hypoxia and acidosis limit neutrophil bacterial killing mechanisms.  Arch Surg. 1997;  132 991-996
  • 27 Machens H G, Mailander P, Pasel J et al.. Flap perfusion after free musculocutaneous tissue transfer: the impact of postoperative complications.  Plast Reconstr Surg. 2000;  105 2395-2399

Peter M VogtM.D. Ph.D. 

Department of Plastic, Hand and Reconstructive Surgery, Hannover Medical School, Podbielskistr

380, D-30659 Hannover, Germany