Results of a Decellularized Porcine Heart Valve Implanted into the Juvenile Sheep Model
DOI:
https://doi.org/10.1532/HSF98.20041140Abstract
Objective: This study was performed to evaluate the possibility of creating a glutaraldehyde-free porcine xenograft to improve long-term durability.
Methods: A decellularized porcine pulmonary valve was implanted into the right ventricular outflow tract of 7 juvenile sheep. Valves were explanted after 3 months (n = 4) and 6 months (n = 3). Evaluation was performed by gross examination, radiography, histology (hematoxylin-eosin and Sirius red staining), and immunohistochemistry. Quantitative determination of calcium content was investigated by atomic absorption spectrometry.
Results: All animals showed fast recovery without complications. At explantation, all decellularized valves showed smooth and pliable leaflets without evidence of thrombosis. The valve wall was also smooth and pliable without hardness. Light microscopy showed a monolayer of host endothelial cells covering the inner surface of the heart valves and repopulation of host fibroblasts into the deeper layers. Sirius red staining enabled visualization of the production of new collagen. Radiographic results showed an absence of calcification, confirmed by the low calcium levels (1.08 ± 0.28 m g/g and 0.73 ± 0.31 m g/g at 3 and 6 months, respectively) revealed by atomic absorption spectrometry.
Conclusions: The results with the juvenile sheep model showed that decellularized heart valves are recellularized in vivo. Host endothelial cells form a monolayer on the inner surface of the valve matrix. Furthermore, host fibroblasts repopulate the valve matrix and produce collagen; thus, a remodeling potential can be expected.
References
Dohmen PM, da Costa F, Pohl P, et al. 2003. Is the juvenile sheep model a suitable model to evaluate tissue engineered cardiovascular grafts? LA Arch Cardiovasc Sci 4:45-53.nDohmen PM, Dushe S, Kern H, Konertz W. 2003. First clinical implantation of a tissue engineered heart valve using a glutaraldehyde free xenogenic scaffold. LA Arch Cardiovasc Sci 4:26-30.nDohmen PM, Liu J, Lembcke A, Konertz W. 2003. Reoperation in a Jehovah's witness 22 years after aortic allograft reconstruction of the right ventricular outflow tract. Tex Heart Inst J 30:146-8.nElkins RC, Dawson PE, Goldstein S, Walsh SP, Black KS. 2001. Decellularized human valve allografts. Ann Thorac Surg 71: S428-32.nElkins RC, Goldstein S, Hewitt CW, et al. 2001. Recellularization of heart valve grafts by a process of adaptive remodeling. Semin Thorac Cardiovasc Surg 13(suppl 1):87-92.nGall KL, Smith SE, Willmette CA, O'Brien MF. 1998. Allograft heart valve viability and valve-processing variables. Ann Thorac Surg 65:1032-8.nRajani B, Mee RB, Ratliff NB. 1998. Evidence for rejection of homograft cardiac valves in infants. J Thorac Cardiovasc Surg 115:111-7.nSchoof PH, Gittenberger Groot AC, de Heer E, Bruijn JA, Hazekamp MG, Huysmans HA. 2000. Remodeling of the porcine pulmonary autograft wall in the aortic position. J Thorac Cardiovasc Surg 120:55-65.nShaddy RE, Hawkins JA. 2002. Immunology and failure of valve allografts in children. Ann Thorac Surg 74:1271-5.nZilla P, von Oppell, Deutsch M. 1998. The endothelium: a key to the future. J Card Surg 8:32-60.nHawkins JA, Breinholt JP, Lambert LM, et al. 2000. Class I and class II anti-HLA antibodies after implantation of cryopreserved allograft material in pediatric patients. J Thorac Cardiovasc Surg 119:324-30.nKonertz W, Koch C, Dohmen PM, Laube H, Rutsch W. 2001. Five year follow up of patients receiving tissue engineered coronary artery bypass grafts. Circulation 104:II-362.nLeyh RG, Wilhelmi M, Rebe P, et al. 2003. In vivo repopulation of xenogeneic and allogeneic acellular valve matrix conduits in the pulmonary circulation. Ann Thorac Surg 75:1457-63.nMitchell RN, Jonas RA, Schoen FJ. 1998. Pathology of explanted cryop reserved allograft heart valves: comparison with aortic valves from orthotopic heart transplants. J Thorac Cardiovasc Surg 115:118-27.n[NIH] National Institutes of Health. 1985. Guide for the care and use of laboratory animals. Washington, DC: US Department of Health, Education and Welfare. Publication nr 85-23.nO'Brien MF, Goldstein S, Walsh S, Black KS, Elkins R, Clarke D. 1999. The SynerGraft valve: a new acellular (nonglutaraldehyde-fixed) tissue heart valve for autologous recellularization: first experimental studies before clinical implantation. Semin Thorac Cardiovasc Surg 11(suppl 1):194-200.nO'Brien MF, Harrocks S, Staffold EG, et al. 2001. The homograft aortic valve: a 29-year, 99.3% follow up of 1,022 valve replacements. J Heart Valve Dis 10:334-44.nBechtel JF, Muller Steinhardt M, Schmidtke C, Brunswik A, Stierle U, Sievers HH. 2003. Evaluation of the decellularized pulmonary valve homograft (SynerGraft). J Heart Valve Dis 12:734-9.nAllen DJ, DiDio DJ, Zacharias A, et al. 1984. Microscopic study of normal parietal pericardium and unimplanted Puig-Zerbini pericardial valvular heterografts. J Thorac Cardiovasc Surg 87:845-55.nChambers JC, Somerville J, Stone S, Ross DN. 1997. Pulmonary auto graft procedure for aortic valve disease. Circulation 96:2206-14.nda Costa FDA, Dohmen P, Lopes SV, et al. 2004. Experimental study with decellularized porcine heterografts: the prosthesis of the future. Rev Bras Cir Cardiovasc 19:74-82.nDignan R, O'Brien M, Hogan P, et al. 2003. Aortic valve allograft structural deterioration is associated with a subset of antibodies to human leukocyte antigens. J Heart Valve Dis 12:382-90.n
