Angiogenic pretreatment to enhance myocardial function after cellular cardiomyoplasty with skeletal myoblasts Mauricio A. Retuerto, BS, James T. Beckmann,

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Angiogenic pretreatment to enhance myocardial function after cellular cardiomyoplasty with skeletal myoblasts Mauricio A. Retuerto, BS, James T. Beckmann, BS, JoAnn Carbray, BS, Gerald Patejunas, PhD, Sorin Sarateanu, MD, Bonnie J. Kane, BS, Beverly Smulevitz, BS, David D. McPherson, MD, Todd K. Rosengart, MD The Journal of Thoracic and Cardiovascular Surgery Volume 133, Issue 2, Pages 478-484.e2 (February 2007) DOI: 10.1016/j.jtcvs.2006.08.073 Copyright © 2007 The American Association for Thoracic Surgery Terms and Conditions

Figure 1 Myocardial infarct perfusion. Perfusion is depicted by Evans blue concentration in region of myocardial infarction 21 days after coronary ligation as function of interval between coronary ligation and adenoviral vector (VEGF) versus saline vehicle (PBS) administration. The Journal of Thoracic and Cardiovascular Surgery 2007 133, 478-484.e2DOI: (10.1016/j.jtcvs.2006.08.073) Copyright © 2007 The American Association for Thoracic Surgery Terms and Conditions

Figure 2 Myocardial infarct mass. Infarct wet weight measured 21 days after coronary ligation is depicted as function of interval between coronary ligation and adenoviral vector (VEGF) versus saline vehicle (PBS) administration as either absolute weight divided by area of infarct (A) or relative (percentage) difference in infarct mass (B). The Journal of Thoracic and Cardiovascular Surgery 2007 133, 478-484.e2DOI: (10.1016/j.jtcvs.2006.08.073) Copyright © 2007 The American Association for Thoracic Surgery Terms and Conditions

Figure 3 Myocardial infarct area. Infarct area measured 21 days after coronary ligation is depicted as function of interval between coronary ligation and adenoviral vector (VEGF) versus saline vehicle (PBS) administration. The Journal of Thoracic and Cardiovascular Surgery 2007 133, 478-484.e2DOI: (10.1016/j.jtcvs.2006.08.073) Copyright © 2007 The American Association for Thoracic Surgery Terms and Conditions

Figure 4 Morphology of myocardial scar as function of various treatments. (A) Saline vehicle administration at time of coronary ligation (day 0); (B) adenoviral vector administration at time of coronary ligation (day 0); (C) saline vehicle administration 7 days after coronary ligation; (D) adenoviral vector administration 7 days after coronary ligation. LV, Left ventricle. The Journal of Thoracic and Cardiovascular Surgery 2007 133, 478-484.e2DOI: (10.1016/j.jtcvs.2006.08.073) Copyright © 2007 The American Association for Thoracic Surgery Terms and Conditions

Figure 5 Mean left ventricular (LV) ejection fraction (EF), as determined by echocardiographic analysis. Group 1 (n = 7) represents adenoviral vector at coronary ligation, myoblasts 3 weeks later. Group 2 (n = 8) represents saline vehicle at coronary ligation, myoblasts 3 weeks later. Group 3 (n = 8) represents saline vehicle at coronary ligation and 3 weeks later. Group 4 (n = 5) represents saline vehicle at coronary ligation, adenoviral vector with myoblasts 3 weeks later. T0, Time of coronary ligation; T1, 3 weeks after coronary ligation; T2, 5 weeks after coronary ligation. The Journal of Thoracic and Cardiovascular Surgery 2007 133, 478-484.e2DOI: (10.1016/j.jtcvs.2006.08.073) Copyright © 2007 The American Association for Thoracic Surgery Terms and Conditions

Figure E1 Photomicrograph demonstrating human alkaline phosphatase–positive myoblasts treated with Elf 97 substrate (Invitrogen, Carlsbad, Calif) indicative of donor cells. The Journal of Thoracic and Cardiovascular Surgery 2007 133, 478-484.e2DOI: (10.1016/j.jtcvs.2006.08.073) Copyright © 2007 The American Association for Thoracic Surgery Terms and Conditions

Figure E2 Two-dimensional echocardiographic images confirm preservation of left ventricular mass in (left) adenovirus-pretreated animals relative to (right) saline-pretreated animals. Arrow depicts anteroapical region receiving cell administration. The Journal of Thoracic and Cardiovascular Surgery 2007 133, 478-484.e2DOI: (10.1016/j.jtcvs.2006.08.073) Copyright © 2007 The American Association for Thoracic Surgery Terms and Conditions

Figure E3 Improvements in ejection fraction in individual subjects at time of cell implantation (Pre Cell) versus 2 weeks later (Post Cell). Group 1 (n = 7) represents adenoviral vector at coronary ligation, myoblasts 3 weeks later. Group 2 (n = 8) represents saline vehicle at coronary ligation, myoblasts 3 weeks later. Group 3 (n = 8) represents saline vehicle at coronary ligation and 3 weeks later. Group 4 (n = 5) represents saline vehicle at coronary ligation, adenoviral vector with myoblasts 3 weeks later. P = .04 for group 1 versus groups 2 and 3. The Journal of Thoracic and Cardiovascular Surgery 2007 133, 478-484.e2DOI: (10.1016/j.jtcvs.2006.08.073) Copyright © 2007 The American Association for Thoracic Surgery Terms and Conditions