Christopher G. A. McGregor, MB, William R

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Presentation transcript:

Cardiac xenotransplantation: Recent preclinical progress with 3-month median survival Christopher G.A. McGregor, MB, William R. Davies, MD, Keiji Oi, MD, Sumeet S. Teotia, MD, Johannes M. Schirmer, MD, Jack M. Risdahl, DVM, PhD, Henry D. Tazelaar, MD, Walter K. Kremers, PhD, Randall C. Walker, MD, Guerard W. Byrne, PhD, John S. Logan, PhD The Journal of Thoracic and Cardiovascular Surgery Volume 130, Issue 3, Pages 844.e1-844.e9 (September 2005) DOI: 10.1016/j.jtcvs.2005.04.017 Copyright © 2005 The American Association for Thoracic Surgery Terms and Conditions

Figure 1 Hematologic analysis of transplant recipients: A, platelet counts; B, hematocrit value; C, total white blood cell counts; D, analysis of CD20+ and CD40+ lymphocytes in mesenteric lymph nodes on POD 0, the day of transplantation, and at the time of rejection or recipient death (Table 1). Data from recipients 1, 2, 3, 6, and 7 are shown. Comparable samples from recipients 4 and 5 were not obtained, and therefore these animals were excluded from this analysis. Control represents the proportion of CD20+ and CD40+ lymphocytes from an untreated baboon. The Journal of Thoracic and Cardiovascular Surgery 2005 130, 844.e1-844.e9DOI: (10.1016/j.jtcvs.2005.04.017) Copyright © 2005 The American Association for Thoracic Surgery Terms and Conditions

Figure 2 Xenograft histology. A, Xenograft of recipient 6 explanted on POD 99, when the recipient died of a pulmonary embolism. The graft shows extensive DXR with large regions of coagulative myocyte necrosis. B, Xenograft of recipient 4 that died of renal failure on POD 64. The section shows minimal evidence of DXR. There is one small focus of myocardium with coagulative necrosis (*) surrounded by well-preserved myocardium. (Hematoxylin and eosin, original magnification 100×.) The Journal of Thoracic and Cardiovascular Surgery 2005 130, 844.e1-844.e9DOI: (10.1016/j.jtcvs.2005.04.017) Copyright © 2005 The American Association for Thoracic Surgery Terms and Conditions

Figure 3 Immunohistochemical staining of explanted cardiac xenografts. A and B are from recipient 6, the same animal shown in Figure 2, A, with severe DXR, and C and D are from recipient 4, the same animal shown in Figure 2, B, with minimal DXR. Intense diffuse staining of endothelial cells in remaining viable myocardium by IgM and IgG is seen in A and B. Diffuse moderate staining of endothelial cells with IgM is seen in C, and focal moderate staining of endothelial cells by IgG is seen in D. Arrows highlight areas shown as insets (Original magnification 100× for each panel, 200× for IgG insets.) The Journal of Thoracic and Cardiovascular Surgery 2005 130, 844.e1-844.e9DOI: (10.1016/j.jtcvs.2005.04.017) Copyright © 2005 The American Association for Thoracic Surgery Terms and Conditions

Figure 4 Serum anti-Gal antibodies in the one animal that survived organ removal on day 137. The graph depicts the fold change in anti-Gal IgM and IgG relative to pretransplantation baseline serum values. The day of organ explantation (137) is indicated by an asterisk. TPC was administered every 3 days before transplantation and after day 30. Daily TPC dosing was given from days 0 to 30, as indicated by the horizontal arrows. The duration of immunosuppression with tacrolimus and sirolimus is indicated by a horizontal arrow extending from POD −6 to 151. The Journal of Thoracic and Cardiovascular Surgery 2005 130, 844.e1-844.e9DOI: (10.1016/j.jtcvs.2005.04.017) Copyright © 2005 The American Association for Thoracic Surgery Terms and Conditions