Focal angiogen therapy using intramyocardial delivery of an adenovirus vector coding for vascular endothelial growth factor 1211 Leonard Y Lee, MD, Shailen R Patel, MD, Neil R Hackett, PhD, Charles A Mack, MD, Dean R Polce, BS, Tarek El-Sawy, BS, Rory Hachamovitch, PhD, Pat Zanzonico, PhD, Timothy A Sanborn, MD, Manish Parikh, PhD, O.Wayne Isom, MD, Ronald G Crystal, MD, Todd K Rosengart, MD The Annals of Thoracic Surgery Volume 69, Issue 1, Pages 14-23 (January 2000) DOI: 10.1016/S0003-4975(99)01102-9
Fig 1 Rat myocardial Ad vector genome levels and VEGF levels over time after intramyocardial administration of the AdGVVEGF121.10 vector. (A) Ad vector genome levels in the apical myocardium, as assessed by TaqMan, relative to the copies of cellular genome. (B) VEGF protein levels in the apical myocardium determined by ELISA expressed as nanograms of VEGF per milligram tissue protein. Values are expressed as the means ± standard error of three animals per data point. The Annals of Thoracic Surgery 2000 69, 14-23DOI: (10.1016/S0003-4975(99)01102-9)
Fig 2 Myocardial Ad vector genome levels in the pig heart 1 h after intramyocardial or intracoronary administration of the AdGVVEGF121.10 vector. The data are presented as the Ad vector genome levels relative to the copies of cellular genome. Values are expressed as the means ± standard error for n = 3 animals in each group. (A) Intramyocardial; (B) intracoronary. The Annals of Thoracic Surgery 2000 69, 14-23DOI: (10.1016/S0003-4975(99)01102-9)
Fig 3 Myocardial VEGF levels in the pig heart 1 day after intramyocardial or intracoronary administration of the AdGVVEGF121.10 vector. Myocardial biopsies were taken for VEGF levels, measured by ELISA, and expressed as nanograms of VEGF protein per milligram tissue protein. Values are expressed as the means ± standard error. (A). Intramyocardial; (B) intracoronary. The Annals of Thoracic Surgery 2000 69, 14-23DOI: (10.1016/S0003-4975(99)01102-9)
Fig 4 Quantitative angiographic assessment of collateral flow to the region of administration of the AdGVVEGF121.10 vector by ex vivo angiography. (A) Shown are representative frames 0, 15, 30, 45, and 60. Small arrows represent circumflex coronary artery, white arrowheads represent the left anterior descending coronary artery, and black arrowhead represents ameroid constrictor. (B) Index of collateral flow. Values are expressed as the means ± standard error for each group. The Annals of Thoracic Surgery 2000 69, 14-23DOI: (10.1016/S0003-4975(99)01102-9)
Fig 5 Representative ex vivo angiograms of pig hearts 28 days after intramyocardial administration of AdGVVEGF121.10 109 pfu or AdNull 109 pfu. (A) AdNull; LAD = left anterior descending artery; (B) AdGVVEGF121.10. The Annals of Thoracic Surgery 2000 69, 14-23DOI: (10.1016/S0003-4975(99)01102-9)
Fig 6 Representative 99mTc-sestamibi SPECT images 28 days after intramyocardial administration of the AdGVVEGF121.10 or AdNull vector to the circumflex territory of the ischemic pig myocardium. Images were obtained at the time of vector administration (day 0) and after 28 days. (A) AdNull; (B and C) AdGVVEGF121.10; (D) semiquantitative 99mTc-sestamibi SPECT imaging regional assessment of circumflex versus septal territory. Values are expressed as the means ± standard error for each group at days 0 and 28 after vector administration. (C = circumflex distribution of the left ventricle; S = septum; ∗ regional ischemia score of zero.) The Annals of Thoracic Surgery 2000 69, 14-23DOI: (10.1016/S0003-4975(99)01102-9)