The Dynamic and Histologic Changes of Variously Fixed Bovine Pericardiums Specimens after Mechanical Fatigue Stimuli

다양한 고정 처리법을 이용한 소 심낭의 기계적 피로 자극 후 역학적 및 조직학적 변화

  • Chang, Hyoung-Woo (Department of Thoracic and Cardiovascular Surgery, Seoul National University Hospital, Seoul National University College of Medicine) ;
  • Kim, Yong-Jin (Department of Thoracic and Cardiovascular Surgery, Seoul National University Hospital, Seoul National University College of Medicine) ;
  • Kim, Soo-Hwan (Seoul National University Hospital Clinical Research Institute, Xenotransplantation Research Center) ;
  • Park, Ji-Eun (Seoul National University Hospital Clinical Research Institute, Xenotransplantation Research Center) ;
  • Park, Chun-Soo (Department of Thoracic and Cardiovascular Surgery, Seoul National University Hospital, Seoul National University College of Medicine) ;
  • Kim, Woong-Han (Department of Thoracic and Cardiovascular Surgery, Seoul National University Hospital, Seoul National University College of Medicine) ;
  • Kim, Kyung-Hwan (Department of Thoracic and Cardiovascular Surgery, Seoul National University Hospital, Seoul National University College of Medicine)
  • 장형우 (서울대학교 의과대학 서울대학교병원 흉부외과학교실) ;
  • 김용진 (서울대학교 의과대학 서울대학교병원 흉부외과학교실) ;
  • 김수환 (서울대학교병원 임상의학연구소, 바이오 이종장기개발사업단) ;
  • 박지은 (서울대학교병원 임상의학연구소, 바이오 이종장기개발사업단) ;
  • 박천수 (서울대학교 의과대학 서울대학교병원 흉부외과학교실) ;
  • 김웅한 (서울대학교 의과대학 서울대학교병원 흉부외과학교실) ;
  • 김경환 (서울대학교 의과대학 서울대학교병원 흉부외과학교실)
  • Published : 2009.04.05

Abstract

Background: As cardiovascular operations become more complex and sophisticated, there is an increasing need for various bioprostheses for use as components of blood vessels and heart valves. We developed a fatigue stimuli test instrument to objectively evaluate the mechanical durability of a bioprosthesis, and we tested several currently known processing methods for bovine pericardium and we then compared the results. Material and Method: Fresh bovine pericardium was collected at the butcher shop with using aseptic technique, and each piece of pericardium was fixated and/or decellularized by 16 representative methods. We measured the permeability and compliance of the processed bovine pericardium samples, and measured them again after exposure to the fatigue stimuli. All the pieces of pericardium underwent microscopic examinations before and after the fatigue stimuli. Result: A mixture of glutaraldehyde and solvent treatment showed better mechanical durability than did the single glutaraldehyde treatment. High concentration glutaraldehyde treatment showed equal or no worse results than did low concentration glutaraldehyde treatment. After SDS (sodium dodecylsulfate) decellularization, the mechanical property of the bioprosthesis became much worse ($20{\sim}190$ times) and the mechanical durability to the fatigue stimuli was also very poor. Conclusion: We obtained the basic durability data after various fixation methods with using a home-made fatigue test instrument.

배경: 심혈관 수술이 발달함에 따라 혈관 또는 판막 등의 일부로써 사용하기 위한 보철편의 필요성이 대두되고 있다. 저자들은 보철편의 기계적 성질을 객관적으로 평가하고 내구성에 대한 정보를 얻기 위하여 피로 자극 시험 장비를 개발하였고, 다양한 방법으로 처리된 우(牛)심낭편을 시험하여 그 결과를 확인하고 서로 비교하여 더 나은 처리방법을 찾고자 하였다. 대상 및 방법: 도살장에서 신선 우심낭편을 무균 채취한 뒤 총 16가지의 대표적인 처리방법으로 우심낭편을 고정 또는 탈세포화 한 뒤 피로 실험 전후로 조직의 투과도와 유순도를 측정하여 비교하였고 또한 광학현미경을 통한 조직검사로 조직 구조의 가시적인 변화 정도를 확인하였다. 결과: 글루타르알데히드 단독으로 고정한 경우에 비해 글루타르알데히드와 용매를 혼합하여 고정한 경우가 더 좋은 기계적 내구성을 보였다. 최근 기성제품에서는 저농도 글루타르알데히드가 널리 쓰이고 있으나, 면역학적 이점이 있을 것으로 생각되는 고농도 글루타르알데히드로 고정한 우심낭편도 기계적 내구성에 문제가 얼었다. 탈세포화는 석회화 예방을 위해 다분히 필요한 과정으로 생각되고 있으나, 흔히 쓰이고 있는 SDS를 미용한 탈세포화는 우심낭편의 기계적 성질을 크게 악화시켜 투과도와 유순도가 $20{\sim}190$배 정도까지 증가하며, 탈세포화를 거친 우심낭편은 기계적 내구성도 매우 떨어져 피로 자극 후 투과도와 유순도가 크게 증가하는 것을 확인할 수 있었다. 결론: 자체 개발한 피로 자극 실험 장비를 이용하여 다양한 방법으로 처리한 심낭편의 내구성을 평가할 수 있었으며 향후 최적의 심낭편 처리방법을 개발하기 위한 기초적인 데이터를 얻을 수 있었다.

Keywords

References

  1. Neethling WM, Hodge AJ, Clode P, et al. A multi-step approach in anti-calcification of glutaraldehyde-preserved bovine pericardium. J Cardiovasc Surg (Torino) 2006;47: 711-8
  2. Garcia Paez JM, Jorge-Herrero E, Carrera A, et al. Chemical treatment and tissue selection: factors that influence the mechanical behaviour of porcine pericardium. Biomaterials 2001;22:2759-67 https://doi.org/10.1016/S0142-9612(01)00019-9
  3. Ahn JH, Kim YJ. Investigation of bovine pericardial heterograft (I) - Concentration of fixatives and tensile strength. Korean J Thorac Cardiovasc Surg 1989;22:373-83
  4. Kim KB, Kim YJ, Rho JR, et al. Investigation of bovine pericardial heterograft (II) - Clinical applications of glutaraldehyde-preserved bovine pericardium. Korean J Thorac Cardiovasc Surg 1990;23:465-73
  5. Kim KB, Kim YJ, Rho JR, et al. Investigation of bovinepericardial heterograft (III) - Experimental evaluation of calcification in glutaraldehyde-preserved bovine pericardium. Korean J Thorac Cardiovasc Surg 1991;24:837-42
  6. Ahn JH, Noh YW, Rhee JH. Pulmonary autograft with right ventricular outflow tract reconstruction in swine model. Korean J Thorac Cardiovasc Surg 1996;29:822-7
  7. Ahn JH, Han JJ, Park SS. Prevention of calcification in bovine pericardial bioprosthesis. Korean J Thorac Cardiovasc Surg 1998;31:560-6
  8. Kim KC, Choi CH, Lee C, et al. Development of porcine pericardial heterograft for clinical application (Microscopic analysis of various fixation methods). Korean J Thorac Cardiovasc Surg 2008;41:295-304
  9. Kim KC, Lee C, Choi CH, et al. Development of porcine pericardial heterograft for clinical application (Tensile strength- thickness). Korean J Thorac Cardiovasc Surg 2008;41:170-6
  10. Gratzer PF, Pereira CA, Lee JM. Solvent environment modulates effects of glutaraldehyde crosslinking on tissue-derived biomaterials. J Biomed Mater Res 1996;31:533-43 https://doi.org/10.1002/(SICI)1097-4636(199608)31:4<533::AID-JBM14>3.0.CO;2-H
  11. Gendler E, Gendler S, Nimni ME. Toxic reactions evoked by glutaraldehyde-fixed pericardium and cardiac valve tissue bioprosthesis. J Biomed Mater Res 1984;18:727-36 https://doi.org/10.1002/jbm.820180703
  12. Weadock K, Olson RM, Silver FH. Evaluation of collagen crosslinking techniques. Biomater Med Devices Artif Organs 1983;11:293-318
  13. Huang-Lee LL, Cheung DT, Nimni ME. Biochemical changes and cytotoxicity associated with the degradation of polymeric glutaraldehyde derived crosslinks. J Biomed Mater Res 1990; 24:1185-201 https://doi.org/10.1002/jbm.820240905
  14. Human P, Zilla P. The possible role of immune responses in bioprosthetic heart valve failure. J Heart Valve Dis 2001;10: 460-6
  15. Zilla P, Brink J, Human P, et al. Prosthetic heart valves: Catering for the few. Biomaterials 2008;29:385-406 https://doi.org/10.1016/j.biomaterials.2007.09.033
  16. O'Brien MF, Stafford EG, Gardner MA, et al. A comparison of aortic valve replacement with viable cryopreserved and fresh allograft valves, with a note on chromosomal studies. J Thorac Cardiovasc Surg 1987;94:812-23
  17. Baskett RJ, Ross DB, Nanton MA, et al. Factors in the early failure of cryopreserved homograft pulmonary valves in children: preserved immunogenicity? J Thorac Cardiovasc Surg 1996;112:1170-8; discussion 1178-9 https://doi.org/10.1016/S0022-5223(96)70130-7
  18. Hoekstra F, Knoop C, Aghai Z, et al. Stimulation of immune- competent cells in vitro by human cardiac valve-derived endothelial cells. Ann Thorac Surg 1995;60:S131-3; discussion S133-4 https://doi.org/10.1016/0003-4975(95)00273-N
  19. Batten P, McCormack AM, Rose ML, et al. Valve interstitial cells induce donor-specific T-cell anergy. J Thorac Cardiovasc Surg 2001;122:129-35 https://doi.org/10.1067/mtc.2001.114940
  20. Courtman DW, Pereira CA, Kashef V, et al. Development of a pericardial acellular matrix biomaterial: biochemical and mechanical effects of cell extraction. J Biomed Mater Res 1994;28:655-66 https://doi.org/10.1002/jbm.820280602
  21. O'Brien MF, Goldstein S, Walsh S, et al. The SynerGraft valve: a new acellular (nonglutaraldehyde-fixed) tissue heart valve for autologous recellularization first experimental studies before clinical implantation. Semin Thorac Cardiovasc Surg 1999;11:194-200
  22. Cebotari S, Mertsching H, Kallenbach K, et al. Construction of autologous human heart valves based on an acellular allograft matrix. Circulation 2002;106:I63-8 https://doi.org/10.1161/01.cir.0000032900.55215.85
  23. Grunkemeier GL, Jamieson WR, Miller DC, et al. Actuarial versus actual risk of porcine structural valve deterioration. J Thorac Cardiovasc Surg 1994;108:709-18
  24. Guerra F, Bortolotti U, Thiene G, et al. Long-term performance of the Hancock porcine bioprosthesis in the tricuspid position. A review of forty-five patients with fourteen-year follow-up. J Thorac Cardiovasc Surg 1990;99:838-45
  25. Carrera San Martin A, Garcia Paez JM, Garcia Sestafe JV, et al. Selection and interaction of biomaterials used in the construction of cardiac bioprostheses. J Biomed Mater Res 1998;39:568-74 https://doi.org/10.1002/(SICI)1097-4636(19980315)39:4<568::AID-JBM10>3.0.CO;2-3
  26. Paez JM, Jorge-Herrero E, Carrera A, et al. Ostrich pericardium, a biomaterial for the construction of valve leaflets for cardiac bioprostheses: mechanical behaviour, selection and interaction with suture materials. Biomaterials 2001;22:2731- 40 https://doi.org/10.1016/S0142-9612(01)00014-X
  27. Carrera San Martin A, Garcia Paez JM, Jorge-Herrero E, et al. Behaviour of the bovine pericardium used in cardiac bioprostheses when subjected to a real fatigue assay. Biomaterials 1993;14:76-9 https://doi.org/10.1016/0142-9612(93)90079-H
  28. Garcia Paez JM, Carrera San Martin A, Jorge-Herrero E, et al. Effect of the suture on the durability of bovine pericardium used in cardiac bioprostheses. Biomaterials 1994;15:172-6 https://doi.org/10.1016/0142-9612(94)90063-9
  29. Gabbay S, Bortolotti U, Wasserman F, et al. Fatigue-induced failure of the Ionescu-Shiley pericardial xenograft in the mitral position. In vivo and in vitro correlation and a proposed classification. J Thorac Cardiovasc Surg 1984;87: 836-44
  30. aez JM, Sanmartin AC, Herrero EJ, et al. Durability of a cardiac valve leaflet made of calf pericardium: fatigue and energy consumption. J Biomed Mater Res A 2006;77:839-4