Prevention of calcification in bovine pericardial bioprosthesis -pretreatment with surfactants-

우심낭편의 석회화 방지에 관한 연구 - 계면활성제 전처치 효과 -

  • 안재호 (이화여자대학교 의과대학 흉부외과) ;
  • 한재진 (이화여자대학교 의과대학 흉부외과) ;
  • 박성수 (이화여자대학교 의과대학 해부학교실)
  • Published : 1998.06.01

Abstract

Background: Bovine pericardial bioprosthesis treated with glutaraldehyde (GA) is one of the most popular prosthetic materials, but late calcific degeneration after implantation is a problem that remains unsolved. For the purpose of mitigating the calcific degeneration, we added MgCl2 into the 0.625% GA solution to compete with calcium for binding to the free aldehyde from GA and pretreated with the surfactants like sodium dodecyl sulfate (SDS) and Triton X-100 before GA fixation for preventing the phospholipid infiltration into the pericardial tissue, the first step of the calcific degeneration. Material and Method: 40 square-shaped pieces of bovine pericardia were fixed in 0.625% GA solution with 4g/L MgCl2 6H2O as a control group (group 1). 40 pieces pretreated with 1% SDS were also fixed in the same GA solution (group 2) and other 40 pieces pretreated with 1% Triton X-100 were prepared with the same method (group 3). After 1 month of fixation these were implanted into the belly of 40 Sprague-Dawley subdermally and extracted 1 month, 2 months, 3 months and 6 months after implantation. With atomic absorption spectrophotometry we measured the deposited calcium amount. Result: 1 month after implantation we could not find any differences between the three groups, but by the 2nd month calcium deposition was 0.921$\pm$0.121 mg/g in group 1, 0.481$\pm$0.037 mg/g in group 2 and 1.369$\pm$0.200 mg/g in group 3. By the 3rd month it was 0.786$\pm$0.080 mg/g in group 1, 0.584$\pm$0.054 mg/g in group 2 and 1.139$\pm$0.188 mg/g in group 3, and on the 6th month 1.623$\pm$0.601 mg/g in group 1,0.501$\pm$0.043 mg/g in group 2 and 1.625$\pm$0.382 mg/g in group 3, with statistical significance in group 2(p<0.05). Conclusion: Pretreatment with SDS showed meaningful calcium mitigation effects on subcutaneously implanted bovine pericardium in the rat models but the neutral type surfactant, Triton X-100, had no positive mitigation effect in this experiment.

서론: 심혈관계 수술 시 이용되는 조직판막 등 glutaraldehyde(GA)에 보존한 이종보철편들은 석회화에 의한 변성으로 환자의 장기성적에 나쁜 영향을 주게 된다. 이에 연구자는 GA 용액에 Mg 염을 첨가, 자유 알데히드와 미리 결합하게 함으로 조직 및 혈중의 칼슘과 반응하는 것을 막아 석회화를 완화하고자 시도하였고 계면활성제로 sodium dodecyl sulfate(SDS)와 Triton X-100을 사용, 전처치하여 GA에 고정, 석회화 완화 효과를 관찰하였다. 대상 및 방법: 우심낭을 정방형 조각으로 만들어 40 조각의 우심낭편은 대조군으로 MgCl2.6H2O를 4g/L 첨가한 0.625% GA 용액에 보존하고(1 군), 40 조각은 SDS에 전처치 후 이 GA 용액에 보존(2 군), 또 다른 40 조각은 Triton X-100에 전처치 후 GA에(3 군) 각각 한달 간 보관한다. 이들을 40 마리의 백서의 복부 피하에 각각 한 조각씩 이식하여 1 개월, 2 개월, 3 개월 및 6 개월 째에 적출, spectrophotometry로 이 우심낭편에 침착한 칼슘을 정량분석하였다. 결과: 이식 후 1 개월에는 세 군 간의 석회화 정도에 차이가 없었으나, 2 개월 부터 차이를 보여 1 군 0.921$\pm$0.121 mg/g, 2 군 0.481$\pm$0.037 mg/g, 3 군 1.369$\pm$0.200 mg/g의 통계적 차이를 보였고(p<0.05), 3 개월에 1 군 0.786$\pm$0.080 mg/g, 2 군 0.584$\pm$0.054 mg/g, 3 군 1.139$\pm$0.188 mg/g, 마지막 6 개월에 1 군 1.623$\pm$0.601 mg/g, 2 군 0.501$\pm$0.043 mg/g, 3 군 1.625$\pm$0.382 mg/g으로 정량되어 2 군에서 유의한 석회화 완화 효과가 관찰되고 있다 (p<0.05). 결론: 음성 계면활성제인 SDS의 전처치로 중기 이상 시간이 경과함에 따라 피하에 이식된 보철편의 석회화가 완화되었으나 중성 계면활성제인 Triton X-100의 전처치로는 완화 효과가 관찰되지 않았다.

Keywords

References

  1. 대흉외지 v.22 소의 심낭을 이용한 이종이식 보철편의 개발(Ⅰ) 안재호;김용진
  2. 대흉외지 v.29 돼지를 이용한 대동맥 판막에서 자가 폐동맥 판막이식 및 우심실 유출로 형성술의 신술식 개발 안재호;노윤우;이조한(등)
  3. 대흉외지 v.23 소의 심낭을 이용한 이종이식 보철편의 개발(Ⅱ) 김기봉;김용진;노준량;서경필
  4. Circulation v.70 no.SUP.Ⅰ Technique for prevention of calcification of valvular bioprosthesis Carpentier A;Nashef A;Carpentier S; Ahmed A;Goussef N
  5. Ann Thorac Surg v.43 Pericardial substitutes: Delayed exploration and findings Opie JC;Larrieu AJ;Cornell IS
  6. Ann Thorac Surg v.60 Time-dependent effect of Glutaraldehyde on the tendency to calcify of both autografts and xenografts Liao K;Frater RWM;Lapietra A(et al)
  7. J Card Surg v.3 The cross-linking and structure modification of the collagen matrix in the design of cardiovascular prosthesis Nimmi ME
  8. Ann Thorac Surg v.46 Inhibition of bioprosthetic heart valve calcification with aminodiphonate convalently bound to residual aldehyde groups Webb CL;Benedict JJ;Schen FJ;Linden LA;Levy RJ
  9. Ann Thorac Surg v.60 Do donor or recipient species influence calcification of bioprosthetic tissues? Carpentier SM;Monier MH;Shen M;Carpentier AF
  10. Ann Thorac Surg v.60 Calcium mitigation in bioprosthetic tissues by iron pretreatment: The challenge of iron leaching Carpentier SM;Carpentier AF;Chen L(et al)
  11. Biomaterials v.15 Anticalcification treatment of pericardial prostheses Chanda J
  12. Ann Thorac Surg v.60 Prevention of calcification of heart valve bioprostheses: An experimental study in rat Chandra J
  13. J Thorac Cardiovasc Surg v.90 Effect of warfarin on calcification ofspontaneously degenerated procine bioprosthetic valves Stein PD;Riddle JM;Kemp SP(et al)
  14. J Biomed Mater Res v.25 Prevention of bioprosthetic heart valve tissue calcification by charge modification: Effects of protamine binding by formaldehyde Golomb G;Ezra V
  15. J Vasc Surg v.19 Cell-free arterial grafts: Morphologic characteristics of aortic isografts , allografts and xenografts in rat Allaire E;Guettier C;Bruneval P;Plissonnier D;Michel JB
  16. Artif Organs v.16 Bovine pericardium versus porcine aortic valve: comparison of tissue biological properties as prosthetic valves Liao K;Seifter E;Hoffman D;Yellin EI;Frater RWM
  17. Am J Cardiol v.25 The normal pericardium Holt JP
  18. J Thorac Cardiovasc Surg v.87 Microscopic syudy of normal parietal pericardium and unimplanted Puig-Zerbini pericardial valvular heterografts Allen DJ;DiDio LJA;Zacharias A(et al)
  19. Am J Cardiol v.46 Histological and ultrastructural features of normal human parietal pericardium Ishihara T;Ferrans VJ;Jones M;Boyce SW;Kawanami O;Roberts WC
  20. Artif Organs v.18 Posttreatment with amino compounds effective in prevention of calcification of glutaraldehyde treated pericardium Chandra J