The Effect of Topical Application of Heparin with Microneedling on Skin Flap Survival

미세바늘을 이용한 헤파린의 국소 도포가 피부 피판 생존에 미치는 영향

  • Yang, Eunjung (Yonsei University, Wonju colleage of medicine) ;
  • Kim, Sugwon (Yonsei University, Wonju colleage of medicine)
  • 양은정 (연세대학교 원주의과대학 성형외과학 교실) ;
  • 김석원 (연세대학교 원주의과대학 성형외과학 교실)
  • Published : 2009.05.15

Abstract

Purpose: The objective of this study was to evaluate the heparin effect for a viability of random - pattern dorsal flap in hairless mouse. Methods: A caudally - based random dorsal flap, measuring $1.5{\times}5cm$, was designed and heparin was applied topically after microneeding. Twenty five male hairless mice were randomly divided into control (Group1, n=5); received only microneedling (Group 2, n=5), only heparin(Group3, n=5), microneedling with saline(Group 4, n=5), and microneedling with heparin group(group5,n=5) to the flap during 7 days. The number of the capillaries were compared between the experimental groups and control group with respect to neovascularization after heparin application using imaging analysis program under hematoxylin - eosin stain. The capillary blood flow was measured by laser Doppler flowmetry. After seven days each animal was evaluated for the percentage area of the flap survival. Mann - Whitnety U test and Kruskal - Wallis statistical analysis of survival relationships was performed. Results: It can be observed increased number of the blood vessels in the experimental groups however it was not statistically significant. Blood flow of the haparin with microneedling group maintained higher than other experimental groups. Treated microneeding and heparin mice were significantly better flap viability than in controls (flap survival 67% and $54.4mm^2$ respectively; p<.01). Positive correlation was shown between flap survival rate and laser Doppler flux value only at first day after surgery. Conclusion: Heparin has a beneficial effect on capillary flow and improve peripheral circulatory disturbances in random pattern flaps.

Keywords

References

  1. Folkman, J: Regulation of angiogenesis: a new function of heparin. Biochem Pharmacol 34: 905, 1985 https://doi.org/10.1016/0006-2952(85)90588-X
  2. Sawhney CP: The role of heparin in restoring the blood supply in ischaemic skin flaps: an experimental study in rabbits. Br Plast Surg 33: 430, 1980 https://doi.org/10.1016/0007-1226(80)90109-5
  3. Wong L, Im MJ, Hoopes JE: Increased survival of island skin flaps by systemic heparin in rats. Ann Plast Surg 26: 221, 1991 https://doi.org/10.1097/00000637-199103000-00003
  4. Wray RC Jr, Young VL: Drug treatment and flap survival. Plast Reconstr Surg 73: 939, 1984 https://doi.org/10.1097/00006534-198406000-00015
  5. Motlekar NA, Youan BB: The quest for non-invasive delivery of bioactive macromolecules: a focus on heparins. J Control Release 113: 91, 2006 https://doi.org/10.1016/j.jconrel.2006.04.008
  6. Goldberg M, Gomez-Orellana I: Challenges for the oral delivery of macromolecules. Nat Rev Drug Discov 2: 289, 2003 https://doi.org/10.1038/nrd1067
  7. Hobson RW 2nd, Wright JG, Fox D, Kerr JC: Heparinization reduces endothelial permeability and hydrogen ion accumulation in a canine skeletal muscle ischemia- reperfusion model. J Vasc Surg 7: 585, 1988 https://doi.org/10.1016/0741-5214(88)90364-3
  8. Benson HA: Transdermal drug delivery: penetration enhancement techniques. Curr Drug Deliv 2: 23, 2005 https://doi.org/10.2174/1567201052772915
  9. Le L, Kost J, Mitragotri S: Combined effect of low- frequency ultrasound and iontophoresis: applications for transdermal heparin delivery. Pharm Res 17: 1151, 2000 https://doi.org/10.1023/A:1026426317413
  10. Weaver JC, Vanbever R, Vaughan TE, Prausnitz MR: Heparin alters transdermal transport associated with electroporation. Biochem Biophys Res Commun 234: 637, 1997 https://doi.org/10.1006/bbrc.1997.6701
  11. Schramm J, Mitragotri S: Transdermal drug delivery by jet injectors: energetics of jet formation and penetration. Pharm Res 19: 1673, 2002 https://doi.org/10.1023/A:1020753329492
  12. Prausnitz MR: Microneedles for transdermal drug delivery. Adv Drug Deliv Rev 56: 581, 2004 https://doi.org/10.1016/j.addr.2003.10.023
  13. Sawada Y, Sugawara M, Hatayama I, Sone K: A study of topical and systemic prostaglandin E1 and survival of experimental skin flaps. Br J Plast Surg 46: 670, 1993 https://doi.org/10.1016/0007-1226(93)90197-J
  14. Heller L, Levin LS, Klitzman B: Laser Doppler flowmeter monitoring of free-tissue transfers: blood flow in normal and complicated cases. Plast Reconstr Surg 107: 1739, 2001 https://doi.org/10.1097/00006534-200106000-00015
  15. Yuen JC, Feng Z: Monitoring free flaps using the laser Doppler flowmeter: five-year experience. Plast Reconstr Surg 105: 55, 2000 https://doi.org/10.1097/00006534-200001000-00009