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Effect of 4-hexylresorcinol on Blood Coagulation and Healing of Injured Vessel in a Rat Model

  • Park, Yong-Tae (Department of Oral and Maxillofacial Surgery, College of Dentistry, Gangneung-Wonju National University) ;
  • Park, Si-Yeok (Department of Oral and Maxillofacial Surgery, College of Dentistry, Gangneung-Wonju National University) ;
  • Kim, Min-Keun (Department of Oral and Maxillofacial Surgery, College of Dentistry, Gangneung-Wonju National University) ;
  • Kim, Seong-Gon (Department of Oral and Maxillofacial Surgery, College of Dentistry, Gangneung-Wonju National University) ;
  • Park, Young-Wook (Department of Oral and Maxillofacial Surgery, College of Dentistry, Gangneung-Wonju National University) ;
  • Kwon, Kwang-Jun (Department of Oral and Maxillofacial Surgery, College of Dentistry, Gangneung-Wonju National University)
  • Received : 2013.08.13
  • Accepted : 2013.09.21
  • Published : 2013.09.30

Abstract

Purpose: For reconstruction of craniomaxillofacial defects caused by tumor, trauma, infection etc, free flap transplantation with microvascular surgery is a very useful method. Thrombus formation at the anastomosis site is the major cause of graft failure. 4-Hexylresorcinol (4-HR) is generally known as an antiseptic and antiparasitic agent. This study was conducted in order to evaluate the effect of 4-HR on blood coagulation in vitro. In addition, we investigated thrombus formation and endothelial repair of an injured vessel in an animal model. Methods: In the in vitro experiment, we compared blood coagulation time between the 4-HR treated group and normal blood. Thirty rats were used for in vivo animal experiments. After exposure of the right femoral vein, a micro vessel clamp was placed and the femoral vein was intentionally cut. Microvascular anastomosis was performed on all rats using 10-0 nylon under microscopy. The animals were divided into two groups. In the experimental group (n=15), 4-HR (250 mg/kg) mixed with olive oil (10 mL/kg) was administered per os daily. Animals in the control group (n=15) were given olive oil only. The animals were sacrificed at three days, seven days, and fourteen days after surgery and rat femoral vein samples were taken. Vascular patency and thrombus formation were investigated just before sacrifice. Histologic analysis was performed under a microscope. Results: Results of an in vitro blood coagulation test showed that coagulation time was delayed in the 4-HR treated group. The results obtained from an in vivo 4-HR administered rat model showed that the patency of all experimental groups was better at thirty minutes, seven days, and fourteen days after microvascular anastomosis than that of the control group at seven and fourteen days after anastomosis, and the amount of thrombus in the experimental groups was much less than that of the control group. Endothelial repair was observed in the histologic analysis. Conclusion: Findings of this study demonstrated that blood coagulation was delayed in the vitro 4-HR treated group. In addition, good vascular patency, anti-thrombotic effect, and repair of venous endothelial cells were observed in the vivo 4-HR administered rat group.

Keywords

References

  1. Stemerman MB, Spaet TH. The subendothelium and thrombogenesis. Bull N Y Acad Med 1972;48:289-301.
  2. Holmsen H, Day HJ, Stormorken H. The blood platelet release reaction. Scand J Haematol Suppl 1969;8:3-26.
  3. Colman RW, editor. Hemostasis and thrombosis: basic principles and clinical practice. Philadelphia, Toronto: Lippincott;1982. p.594.
  4. Eddy CA, Laufe LE, Dunn RL, Gibson JW. The use of prostacyclin analogue-containing suture for the prevention of postoperative venous thrombosis in the rat. Plast Reconstr Surg 1986;78:504-12. https://doi.org/10.1097/00006534-198610000-00012
  5. Fu K, Izquierdo R, Hubbard T, Fareed J. Modified crush-avulsion anastomosis model on the rat femoral vein. Microsurgery 1995;16:536-41. https://doi.org/10.1002/micr.1920160806
  6. Cooley BC, Hansen FC. Microvascular repair following local crush and avulsion vascular injury. Microsurgery 1985;6:46-8. https://doi.org/10.1002/micr.1920060109
  7. Fujiwara Y, Cohn LH, Adams D, Collins JJ Jr. Use of Gortex grafts for replacement of the superior and inferior venae cavae. J Thorac Cardiovasc Surg 1974;67:774-9.
  8. Haimovivi H, Zinicola N, Noorani M, Hoffert PW. Vein grafts in the venous system. Arch Surg 1963;87:542-7. https://doi.org/10.1001/archsurg.1963.01310160004002
  9. Todd RS, Sive EB, Dejode LR, Danese C, Howard JM. Replacement of segments of the venous system. Arch Surg 1963;87:998-1002. https://doi.org/10.1001/archsurg.1963.01310180114020
  10. Brais M, Bertranou E, Brassard A, Stanley P, Chartrand C. Effect of dextran on patency of pericardial tubular graft of the superior vena cava in the dog. J Thorac Cardiovasc Surg 1973;65:296-303.
  11. Hergrueter CA, Handren J, Kersh R, May JW Jr. Human recombinant tissue type plasminogen activator and its effect on microvascular thrombosis in the rabbit. Plast Reconstr Surg 1988;81:418-24. https://doi.org/10.1097/00006534-198803000-00019
  12. Warkentin TE. Current agents for the treatment of patients with heparin-induced thrombocytopenia. Curr Opin Pulm Med 2002;8:405-12. https://doi.org/10.1097/00063198-200209000-00011
  13. Greenberg BM, Masem M, Wang YX, Rubin P, May JW Jr. Efficacy of intraarterial heparin in maintaining microvascular patency: an experimental model. Plast Reconstr Surg 1991;87:933-40. https://doi.org/10.1097/00006534-199105000-00020
  14. Oh K, Park HB, Byoun OJ, et al. Epithelial transglutaminase 2 is needed for T cell interleukin-17 production and subsequent pulmonary inflammation and fibrosis in bleomycin-treated mice. J Exp Med 2011;208:1707-19. https://doi.org/10.1084/jem.20101457
  15. Evans RT, Baker PJ, Coburn RA, Fischman SL, Genco RJ. In vitro antiplaque effects of antiseptic phenols. J Periodontol 1977;48:156-62. https://doi.org/10.1902/jop.1977.48.3.156
  16. Martinez-Alvarez O, Lopez-Caballero ME, Montero P, Gomez-Guillen MC. Spraying of 4-hexylresorcinol based formulations to prevent enzymatic browning in Norway lobsters (Nephrops norvegicus) during chilled storage. Food Chemistry 2007;100:147-55. https://doi.org/10.1016/j.foodchem.2005.09.031
  17. Rabbani GH, Gilman RH, Kabir I, Mondel G. The treatment of Fasciolopsis buski infection in children: a comparison of thiabendazole, mebendazole, levamisole, pyrantel pamoate, hexylresorcinol and tetrachloroethylene. Trans R Soc Trop Med Hyg 1985;79:513-5. https://doi.org/10.1016/0035-9203(85)90081-1
  18. Kim SG, Jeong JH, Park YW, et al. 4-Hexylresorcinol inhibits transglutaminase-2 activity and has synergistic effects along with cisplatin in KB cells. Oncol Rep 2011;25:1597-602.
  19. Nylen CO. The microscope in aural surgery, its first use and later development. Acta Otolaryngol Suppl 1954;116:226-40.
  20. Jacobson JH, Suarez EL. Microsurgery in anastomosis of small vessels. Surg Forum 1960;11:243-5.
  21. Romano JE, Biel MA. Thrombolysis in microvascular surgery using tissue-type plasminogen activator. Arch Otolaryngol Head Neck Surg 1989;115:1318-21. https://doi.org/10.1001/archotol.1989.01860350052014
  22. Harashina T. Analysis of 200 free flaps. Br J Plast Surg 1988;41:33-6. https://doi.org/10.1016/0007-1226(88)90141-5
  23. Shaw WW, Converse JM. A survey of 2680 free flaps: survival, donor site and application among experienced microvascular surgeons. Plast Surg Forum 1987;4:93-9.
  24. Khouri RK, Cooley BC, Kenna DM, Edstrom LE. Thrombosis of microvascular anastomoses in traumatized vessels: fibrin versus platelets. Plast Reconstr Surg 1990;86:110-7. https://doi.org/10.1097/00006534-199007000-00017
  25. Adams WP Jr, Ansari MS, Hay MT, et al. Patency of different arterial and venous end-to-side microanastomosis techniques in a rat model. Plast Reconstr Surg 2000;105:156-61. https://doi.org/10.1097/00006534-200001000-00026
  26. Acland R. Thrombus formation in microvascular surgery: an experimental study of the effects of surgical trauma. Surgery 1973;73:766-71.
  27. Li X, Cooley BC. Effect of anticoagulation and inhibition of platelet aggregation on arterial versus venous microvascular thrombosis. Ann Plast Surg 1995;35:165-9. https://doi.org/10.1097/00000637-199508000-00009
  28. Converse JM. Reconstructive plastic surgery: principles and procedures in correction, reconstruction and transplantation. 2nd ed. Philadelphia: W.B. Saunders; 1977. p.349.
  29. Acland R. Prevention of thrombosis in microvascular surgery by the use of magnesium sulphate. Br J Plast Surg 1972;25:292-9. https://doi.org/10.1016/S0007-1226(72)80066-3
  30. Zinberg EM, Choo DI, Zotter LA. Effect of heparinized irrigating solutions on patency of experimental microvascular anastomoses. Microsurgery 1989;10:103-7. https://doi.org/10.1002/micr.1920100205
  31. Li X, Cooley BC, Gould JS. Influence of topical heparin on stasis-induced thrombosis of microvascular anastomoses. Microsurgery 1992;13:72-5. https://doi.org/10.1002/micr.1920130205
  32. Rooks MD, Rodriguez J Jr, Blechner M, Zusmanis K, Hutton W. Comparative study of intraarterial and intravenous anticoagulants in microvascular anastomoses. Microsurgery 1994;15:123-9. https://doi.org/10.1002/micr.1920150207
  33. Glimelius B, Busch C, Hook M. Binding of heparin on the surface of cultured human endothelial cells. Thromb Res 1978;12:773-82. https://doi.org/10.1016/0049-3848(78)90271-2
  34. Samuels PB, Webster DR. The role of venous endothelium in the inception of thrombosis. Ann Surg 1952;136:422-38.
  35. Hiebert LM, Jaques LB. The observation of heparin on endothelium after injection. Thromb Res 1976;8:195-204. https://doi.org/10.1016/0049-3848(76)90262-0
  36. Essien EM, Cazenave JP, Moore S, Mustard JF. Effect of heparin and thrombin on platelet adherence to the surface of rabbit aorta. Thromb Res 1978;13:69-78. https://doi.org/10.1016/0049-3848(78)90111-1
  37. National Toxicology Program. NTP toxicology and carcinogenesis studies of 4-hexylresorcinol (CAS No. 136-77-6) in F344/N rats and B6C3F1 mice (Gavage Studies). Natl Toxicol Program Tech Rep Ser 1988;330:1-166.
  38. Leonard V. The significance of hexylresorcinol and its homologues in relation to the problem of internal antisepsis. Science 1925;62:408-12. https://doi.org/10.1126/science.62.1610.408
  39. Young CC, Damon SR. Laboratory: the use of hexylresorcinol in the treatment of typhoid carriers. Am J Public Health (NY) 1927;17:279-80. https://doi.org/10.2105/AJPH.17.3.279

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