Experimental Assessment of Hemostatic Agents: Comparison with New Developed Chitosan-Based Material

신개발 키토산 제재의 지혈 효과에 대한 비교

  • Cho, Young-Kyoo (Department of Plastic and Reconstructive Surgery, Graduate School of Medicine, Kyungpook National University) ;
  • Lee, Sang-Yun (Department of Plastic and Reconstructive Surgery, Graduate School of Medicine, Kyungpook National University) ;
  • Kim, Tae-Jung (Department of Plastic and Reconstructive Surgery, Graduate School of Medicine, Kyungpook National University) ;
  • Lim, Hyun-Ju (Department of Advanced Organic Materials Science and Engineering, Kyungpook National University) ;
  • Oh, Eun-Jung (Department of Advanced Organic Materials Science and Engineering, Kyungpook National University) ;
  • Lee, Soo-Bok (Fiber & Tech Co.) ;
  • Choi, Kang-Young (Department of Plastic and Reconstructive Surgery, Graduate School of Medicine, Kyungpook National University) ;
  • Yang, Jung-Dug (Department of Plastic and Reconstructive Surgery, Graduate School of Medicine, Kyungpook National University) ;
  • Cho, Byung-Chae (Department of Plastic and Reconstructive Surgery, Graduate School of Medicine, Kyungpook National University) ;
  • Chung, Ho-Yun (Department of Plastic and Reconstructive Surgery, Graduate School of Medicine, Kyungpook National University)
  • 조영규 (경북대학교 의과대학 성형외과학교실) ;
  • 이상윤 (경북대학교 의과대학 성형외과학교실) ;
  • 김태정 (경북대학교 의과대학 성형외과학교실) ;
  • 임현주 (경북대학교 기능물질공학과) ;
  • 오은정 (경북대학교 기능물질공학과) ;
  • 이수복 (텍산메드테크(주)기술연구소) ;
  • 최강영 (경북대학교 의과대학 성형외과학교실) ;
  • 양정덕 (경북대학교 의과대학 성형외과학교실) ;
  • 조병채 (경북대학교 의과대학 성형외과학교실) ;
  • 정호윤 (경북대학교 의과대학 성형외과학교실)
  • Received : 2011.03.23
  • Accepted : 2011.06.07
  • Published : 2011.07.10

Abstract

Purpose: Many hemostatic agents and dressings have been tested with variable degree of success. Chitosan has a positive charge, it attracts red blood cells, which have a negative charge. Our goal is to test the efficacy of new developed chitosan-based hemostatic materials in providing durable hemostasis in a high-flow arterial wound model. Methods: We compared each group with SD rats motality tests and in vitro blood compatibility test by blood clotting index (BCI). We devided the SD rats into 6 groups (N =15) by type of hemostatic agents. A: 100% nonwoven chitosan (degree of the deacetylation: 90%). B: 50% N-acetylation on nonwoven of chitosan gel (degree of the deacetylation: 50%). C: 60% N-acetylation on nonwoven of chitosan ge (degree of the deacetylation: 40%)l. D: Cutanplast$^{(R)}$. E: HemCon$^{(R)}$ F: Gauze. In vivo test, a proximal arterial injury was created in unilateral femoral arteries of 90 anesthetized SD rats. Each materials was made same size and thickness then applied to the injury site for 3 minutes. In vitro test, we compared each group with BCI in human blood. Results: In vivo test, group A showed lower motality rate of 46% than any other groups, Group B and C showed lower motality rate of 60% than group D and E's motality rate of 66%. In vitro test, BCI of group A ($30.6{\pm}1.2$) and B ($29.3{\pm}1.0$) were showed nearly about group D ($29.1{\pm}1.8$) and E ($27.4{\pm}1.6$). Group C ($37.1{\pm}2.0$) showed higher BCI than group A and B, it means group C decreased blood clotting. Conclusion: In conclusion, this study suggests a newly developed chitosan-based hemostatic materials induced durable hemostasis and increased blood clotting, and are considered as effective biologic hemostatic agents.

Keywords

References

  1. Berger J, Reist M, Mayer JM, Felt O, Gurny R: Structure and interactions in chitosan hydrogels formed by complexation or aggregation for biomedical applications or aggregation for biomedical applications. Eur J Pharm Biopharm 57: 35, 2004 https://doi.org/10.1016/S0939-6411(03)00160-7
  2. Klokkevold PR, Fukayama H, Sung EC, Bertolami CN: The effect of chitosan (poly-N-Acetyl Glucosamine) on Lingual Hemostasis in Heparinized Rabbits. J Oral Maxillofac Surg 57: 49, 1999 https://doi.org/10.1016/S0278-2391(99)90632-8
  3. Shih MF, Shau MD, Chang MY, Chiou SK, Chang JK, Cherng JY: Platelet absorption and hemolytic properties of liquid crystal/composite polymers. Int J Pharm 327: 117, 2006 https://doi.org/10.1016/j.ijpharm.2006.07.043
  4. Spotnitz WD: Active and mechanical hemostatic agents. Surgery 142: 34, 2007 https://doi.org/10.1016/j.surg.2007.06.024
  5. Fergusson DA, Hebert PC, Mazer CD, Fremes S, MacAdams C, Murkin JM, Teoh K, Duke PC, Arellano R, Blajchman MA, Bussieres JS, Cote D, Karski J, Martineau R, Robblee JA, Rodger M, Wells G, Clinch J, Pretorius R: A comparison of aprotinin and lysine analogues in high-risk cardiac surgery. N Engl J Med 358: 2319, 2008 https://doi.org/10.1056/NEJMoa0802395
  6. Seyednejad H, Imani M, Jamieson T, Seifalian AM: Topical haemostatic agent. Br J Surg 95: 1197, 2008 https://doi.org/10.1002/bjs.6357
  7. Hoffmeister FS, Wenner C, Wilkens HJ, Mukhtar F: Effect of N-acetyl-D-Glucosamine on wound healing of surgical wounds and on mitochondrial phosphorylation uncoupled by dinitrophenol. Surgery 56: 1129, 1964
  8. Prudden JF, Migel P, Hanson P, Friedrich L, Balassa L: The discovery of potent pure chemical wound-healing accelerator. Am J Surg 119: 560, 1970 https://doi.org/10.1016/0002-9610(70)90175-3
  9. Okamoto Y, Shibazaki K, Minami S, Matsuhashi A, Tanioka S, Shigemasa Y: Evaluation of chitin and chitosan an open wound healing in dogs. J Vet Med Sci 57: 851, 1995 https://doi.org/10.1292/jvms.57.851
  10. Kheirabadi BS, Acheson EM, Deguzman R, Sondeen JL, Ryan KL, Delgado A, Dick EJ Jr, Holcomb JB: Hemostatic efficacy of two advanced dressings in an aortic hemorrhage model in Swine. J Trauma 59: 25, 2005 https://doi.org/10.1097/01.TA.0000171458.72037.EE
  11. Gustafson SB, Fulkerson P, Bildfell R, Aguilera L, Hazzard TM: Chitosan dressing provides hemostasis in swine femoral arterial injury model. Prehosp Emerg Care 11: 172, 2007 https://doi.org/10.1080/10903120701205893
  12. Wedmore I, McManus JG, Pusateri AE, Holcomb JB: A special report on chitosan-based hemostatic dressing: Experience in current combat operations. J Trauma 60: 655, 2006 https://doi.org/10.1097/01.ta.0000199392.91772.44
  13. Yang J, Tian F, Wang Z, Wang Q, Zeng YJ, Chen SQ: Effect of chitosan molecular weight and deacetylation degree on hemostasis. J Biomed Mater Res B Appl Biomater 84: 131, 2008
  14. Sugamori T, Iwase H, Maeda M, Inoue Y, Kurosawa H: Local hemostatic effects of microcrystalline partially deacetylated chitin hydrochloride. J Biomed Mater Res 49: 225, 2000 https://doi.org/10.1002/(SICI)1097-4636(200002)49:2<225::AID-JBM10>3.0.CO;2-V
  15. Brandenberg G, Leibrock LG, Shuman R, Malette WG, Quigley H: Chitosan: A new topical hemostatic agent for diffuse bleeding in brain tissue. Neurosurgery 15: 9, 1984 https://doi.org/10.1227/00006123-198407000-00004