Decellularization reduces calcification while improving both durability and 1-year functional results of pulmonary homograft valves in juvenile sheep

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Volume 57, Issue 2, Pages (October 2000)

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Volume 57, Issue 2, Pages (October 2000)

The Journal of Thoracic and Cardiovascular Surgery

Discussion The Journal of Thoracic and Cardiovascular Surgery

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Decellularization reduces calcification while improving both durability and 1-year functional results of pulmonary homograft valves in juvenile sheep Richard A. Hopkins, MD, Alyce Linthurst Jones, MS, RAC, Lloyd Wolfinbarger, PhD, Mark A. Moore, PhD, Arthur A. Bert, MD, Gary K. Lofland, MD The Journal of Thoracic and Cardiovascular Surgery Volume 137, Issue 4, Pages 907-913.e4 (April 2009) DOI: 10.1016/j.jtcvs.2008.12.009 Copyright © 2009 The American Association for Thoracic Surgery Terms and Conditions

Figure 1 Histology of cryopreserved pulmonary valve allograft explanted at 52 weeks. A, Micrograph depicting the presence of dystrophic calcification at the base of the cusp extending into the wall of the pulmonary artery. (Original magnification 100×, von Kossa stain.) B, Histologic section demonstrating the loss of cuspal cellularity after 12 months of implantation. (Original magnification 100×, hematoxylin and eosin.) The Journal of Thoracic and Cardiovascular Surgery 2009 137, 907-913.e4DOI: (10.1016/j.jtcvs.2008.12.009) Copyright © 2009 The American Association for Thoracic Surgery Terms and Conditions

Figure 2 Histology of decellularized a pulmonary valve allograft explanted at 52 weeks. A, Low-magnification view depicting the recellularization of the pulmonary artery and basal region of the cusp. Pannus is seen on the luminal surface of the pulmonary artery extending onto the inflow surface of the cusp. Note the presence of focal endothelialization on the outflow surface of the cusp. (Original magnification 100×, hematoxylin and eosin.) B, Higher-magnification view showing rare focal sites of recellularization of the cusp. (Original magnification 200×, Movat pentachrome stain [collagens, yellow; elastic fibers, black.]) The Journal of Thoracic and Cardiovascular Surgery 2009 137, 907-913.e4DOI: (10.1016/j.jtcvs.2008.12.009) Copyright © 2009 The American Association for Thoracic Surgery Terms and Conditions

Figure 3 Immunohistochemistry of decellularized pulmonary valve allograft explanted at 52 weeks. A, Basal region of the cusp and pannus on the luminal surface of the pulmonary artery depicting the presence of α-smooth muscle actin–immunoreactive cells (green). 4′-6-Diamidino-2-phenylindole dihydrochloride–stained nuclei are shown in blue. (Original magnification 100×.) B, Histologic section of the pulmonary artery demonstrating the extent of recellularization by heat shock protein 47 (collagen chaperon protein with obligatory expression when cells are actively synthesizing new collagen)–immunoreactive cells in the arterial wall and within pannus on the luminal surface. Heat shock protein 47 indicates active collagen synthesis. Together, heat shock protein 47 and α-smooth muscle actin suggest a myofibroblast phenotype consistent with valve interstitial cells. 4′-6-Diamidino-2-phenylindole dihydrochloride–stained nuclei are shown in cyan. (Original magnification 200×.) The Journal of Thoracic and Cardiovascular Surgery 2009 137, 907-913.e4DOI: (10.1016/j.jtcvs.2008.12.009) Copyright © 2009 The American Association for Thoracic Surgery Terms and Conditions

Figure 4 Echocardiogram of juvenile sheep. Sagittal view of right ventricular outflow tract traditional, clinically analogous, cryopreserved allograft obtained 20 weeks after implantation. Note calcium in the leaflets (circles) and conduit walls (arrows). The Journal of Thoracic and Cardiovascular Surgery 2009 137, 907-913.e4DOI: (10.1016/j.jtcvs.2008.12.009) Copyright © 2009 The American Association for Thoracic Surgery Terms and Conditions

Body surface area (BSA) distribution per treatment over time for weeks 10, 20, 35, and 52. Box plots of 1 years' growth (body surface area) for each arm are shown, with individual points per treatment at weeks 10, 20, 37, and 52. Means are connected. There were no significant differences in the rates of growth among the 3 arms over time (P = .145). The Journal of Thoracic and Cardiovascular Surgery 2009 137, 907-913.e4DOI: (10.1016/j.jtcvs.2008.12.009) Copyright © 2009 The American Association for Thoracic Surgery Terms and Conditions

Ovine panel reactive antibody scatter plots over the 1-year study Ovine panel reactive antibody scatter plots over the 1-year study. Scatter plots of panel reactive antibody data for 3 arms over the course of 52 weeks are shown: A, major histocompatibility complex I; B, major histocompatibility complex II. The range of points could not be statistically fit. MFI, Mean fluorescence intensity. The Journal of Thoracic and Cardiovascular Surgery 2009 137, 907-913.e4DOI: (10.1016/j.jtcvs.2008.12.009) Copyright © 2009 The American Association for Thoracic Surgery Terms and Conditions