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Neovasculogenic Therapy to Augment Perfusion and Preserve Viability in Ischemic Cardiomyopathy  Pavan Atluri, MD, George P. Liao, MB, Corinna M. Panlilio,

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Presentation on theme: "Neovasculogenic Therapy to Augment Perfusion and Preserve Viability in Ischemic Cardiomyopathy  Pavan Atluri, MD, George P. Liao, MB, Corinna M. Panlilio,"— Presentation transcript:

1 Neovasculogenic Therapy to Augment Perfusion and Preserve Viability in Ischemic Cardiomyopathy 
Pavan Atluri, MD, George P. Liao, MB, Corinna M. Panlilio, BA, Vivian M. Hsu, BA, Matthew J. Leskowitz, Kevin J. Morine, BA, Jeffrey E. Cohen, BA, Mark F. Berry, MD, Erik E. Suarez, MD, Danielle A. Murphy, BS, William M.F. Lee, MD, PhD, Timothy J. Gardner, MD, H. Lee Sweeney, PhD, Y. Joseph Woo, MD  The Annals of Thoracic Surgery  Volume 81, Issue 5, Pages (May 2006) DOI: /j.athoracsur Copyright © 2006 The Society of Thoracic Surgeons Terms and Conditions

2 Fig 1 Representative plots after flow cytometric analysis of circulating blood in ischemic cardiomyopathic rats 3 weeks after therapy with GMCSF/SDF. (A) Dot plot of forward and side scatter determination of the lymphocyte subpopulation, representative gate for lymphocytes is visualized. (B) Histogram of 7AAD labeled lymphocyte cell viability. A representative, gated viable cell population is delineated. (C) EPC density in a representative saline control animal as determined by colabeling of VEGFR2 and CD34. (D) EPC density in a representative GMCSF/SDF treated animal as determined by colabeling of VEGFR2 and CD34. (AAD = amino-actinomycin D; EPC = endothelial progenitor cell; GMCSF/SDF = granulocyte-macrophage colony stimulating factor/stromal cell-derived factor-1α; VEGFR2 = vascular endothelial growth factor receptor 2.) The Annals of Thoracic Surgery  , DOI: ( /j.athoracsur ) Copyright © 2006 The Society of Thoracic Surgeons Terms and Conditions

3 Fig 2 (Left) (A) Representative quadruple immunofluorescent staining of saline control treated borderzone myocardium: green = PECAM, vessels (green arrow); red = PCNA, proliferating vasculature (red arrow); yellow = α-smooth muscle actin, pericyte lined vessel (yellow arrow); blue = DAPI, nuclei. (B) Representative quadruple immunofluorescent staining of GMCSF/SDF treated borderzone myocardium (63× oil magnification, z-series, Zeiss LSM-510 Meta Confocal microscope). (Right) Graphic and tabulated quantitative vascular borderzone data are displayed for each group. (DAPI = 4’,6-diamidino-2-phenylindole; GMCSF/SDF = granulocyte-macrophage colony stimulating factor/ stromal cell-derived factor; PCNA = proliferating cell nuclear antigen; PECAM = platelet-endothelial cell adhesion molecule.) The Annals of Thoracic Surgery  , DOI: ( /j.athoracsur ) Copyright © 2006 The Society of Thoracic Surgeons Terms and Conditions

4 Fig 3 (Top) Three-dimensional reconstruction of image stacks obtained with confocal microscopy of (A) normal myocardium, (B) control, saline treated, borderzone myocardium, and (C) GMCSF/SDF treated borderzone myocardium (25× air magnification, z-series, Zeiss LSM-510 Meta Confocal microscope). (Bottom) Graphic representation of functional, perfused vessel density in saline control and GMCSF/SDF treated borderzone myocardium. (GMCSF/SDF = granulocyte-macrophage colony stimulating factor/stromal cell-derived factor.) The Annals of Thoracic Surgery  , DOI: ( /j.athoracsur ) Copyright © 2006 The Society of Thoracic Surgeons Terms and Conditions

5 Fig 4 Borderzone myocardial ATP levels in saline control and GMCSF/SDF treated ischemic cardiomyopathic hearts. (ATP = adenosine triphosphate; GMCSF/SDF = granulocyte-macrophage colony stimulating factor/stromal cell-derived factor.) The Annals of Thoracic Surgery  , DOI: ( /j.athoracsur ) Copyright © 2006 The Society of Thoracic Surgeons Terms and Conditions

6 Fig 5 (Top) TUNEL labeled apoptotic nuclei within the borderzone (arrow) of (A) saline control and (B) GMCSF/SDF treated ischemic cardiomyopathic animals. (Bottom) Graphic representation of fraction of apoptotic cells in the borderzone of control and GMCSF/SDF treatment groups. (GMCSF/SDF = granulocyte-macrophage colony stimulating factor/stromal cell-derived factor; TUNEL = terminal deoxynucleotidyl transferase mediated dUTP nick end labeling.) The Annals of Thoracic Surgery  , DOI: ( /j.athoracsur ) Copyright © 2006 The Society of Thoracic Surgeons Terms and Conditions

7 Fig 6 (Top) Representative images of normal, remote myocardium and borderzone myocardium treated with saline control or GMCSF/SDF (hematoxylin and eosin stain). (Bottom) Myofilament density within the ischemic borderzone and normal right ventricular myocardium (GMCSF/SDF = granulocyte-macrophage colony stimulating factor/stromal cell-derived factor; high power field = 40× magnification). The Annals of Thoracic Surgery  , DOI: ( /j.athoracsur ) Copyright © 2006 The Society of Thoracic Surgeons Terms and Conditions

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