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Life-supporting function of genetically modified swine lungs in baboons
Bao-Ngoc H. Nguyen, MD, Agnes M. Azimzadeh, PhD, Tianshu Zhang, MD, PhD, Guosheng Wu, MD, PhD, Henk-Jan Shuurman, PhD, David H. Sachs, MD, David Ayares, PhD, James S. Allan, MD, Richard N. Pierson, MD The Journal of Thoracic and Cardiovascular Surgery Volume 133, Issue 5, Pages (May 2007) DOI: /j.jtcvs Copyright © 2007 The American Association for Thoracic Surgery Terms and Conditions
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Figure 1 Pulmonary vascular resistance (PVR) (A) and plasma levels of complement fragments C3a (B) of all lung recipients. Time −30 represents the initial revascularization of the grafts. Time 0 marks the time when right pulmonary artery to the native lung was clamped and the life-supporting function of the grafts was assessed. C3a levels are expressed as the amount of complement fragments produced above the baseline (Δ). The legend in this figure applies to all following figures. The long-dash line represents the allogenic lung. Two short-dash lines stand for membrane cofactor protein (MCP) lungs, and three solid lines for galactosyl transferase knockout (GalT-KO) lungs. Open symbols represent nonfunctional lungs and filled symbols represent lungs that were able to support life. The Journal of Thoracic and Cardiovascular Surgery , DOI: ( /j.jtcvs ) Copyright © 2007 The American Association for Thoracic Surgery Terms and Conditions
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Figure 2 Platelet and coagulation cascade activation profile of all lung recipients. Symbols correlate with those described in Figure 1. Platelet activation was assessed by quantifying platelet sequestration from circulation measured by automated complete blood count (A), expression of CD62P marker (B), and release of beta-thromboglobulin (BTG) from α granules (C). Activation of the coagulation cascade was detected by the formation of thrombin measured by fragments 1+2 (F1+2) (D). All data are expressed as change from the baseline (Δ). The Journal of Thoracic and Cardiovascular Surgery , DOI: ( /j.jtcvs ) Copyright © 2007 The American Association for Thoracic Surgery Terms and Conditions
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Figure 3 Neutrophil (A) and monocyte (B) sequestration from circulation. Symbols correlate with those described in Figure 1. Cell numbers are expressed as percent remaining in circulation using the cell counts before graft revascularization as the baseline. The Journal of Thoracic and Cardiovascular Surgery , DOI: ( /j.jtcvs ) Copyright © 2007 The American Association for Thoracic Surgery Terms and Conditions
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Figure 4 Hematoxylin and eosin histologic studies of lung biopsy specimens. Allogenic lung (A) at 24 hours showed normal lung histologic features with thin alveolar septae and no pulmonary edema or intravascular thrombosis. Membrane cofactor protein lung + bivalirudin (B) showed severe interstitial/alveolar hemorrhage extending to the airway but no intravascular thrombosis. GalT-KO lung showed significant intravascular thrombosis (C) and severe septal vascular congestion (D) at failure. The Journal of Thoracic and Cardiovascular Surgery , DOI: ( /j.jtcvs ) Copyright © 2007 The American Association for Thoracic Surgery Terms and Conditions
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Figure 5 Immunohistochemistry staining for platelet deposition (CD41) of lung biopsy specimens. The green and red colors represent von Willebrand factor (endothelial marker) and CD41 (platelet marker), respectively. Allogenic lung (A and B) at 24 hours showed essentially no platelet deposition. Likewise, GalT-KO lungs at 30 minutes (C and D) exhibited minimal platelet deposition. However, at lung failure (E and F), there was prominent platelet deposition (red) in association with alveolar septal endothelium (green) in the GalT-KO lung. The Journal of Thoracic and Cardiovascular Surgery , DOI: ( /j.jtcvs ) Copyright © 2007 The American Association for Thoracic Surgery Terms and Conditions
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