Takayoshi Yamaki1, Hans J de Haas2,3, Nobuhiro Tahara4, Artiom Petrov2, Dilbahar Mohar5, Nezam Haider2, Jun Zhou5, Atsuko Tahara4, Yasuchika Takeishi1, Hendrikus H Boersma3,6, Tiziano Scarabelli2, Annapoorna Kini2, H William Strauss2, Jagat Narula7. 1. Department of Cardiovascular Medicine, Fukushima Medical University, Fukushima, Japan. 2. The Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY, 10029, USA. 3. Department of Nuclear Medicine and Molecular Imaging, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. 4. Department of Medicine, Division of Cardio-Vascular Medicine, Kurume University School of Medicine, Kurume, Japan. 5. Division of Cardiology, University of California, Irvine, CA, USA. 6. Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. 7. The Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY, 10029, USA. narula@mountsinai.org.
Abstract
BACKGROUND: Preclinical studies indicate that minocycline protects against myocardial ischemia/reperfusion injury. In these studies, minocycline was administered before ischemia, which can rarely occur in clinical practice. The current study aimed to evaluate cardioprotection by minocycline treatment upon reperfusion. METHODS: Rabbits were subjected to myocardial ischemia/reperfusion injury and received either intravenous minocycline (n = 8) or saline (n = 8) upon reperfusion. Cardiac cell death was assessed by in vivo micro-SPECT/CT after injection of Indium-111-labeled 4-(N-(S-glutathionylacetyl)amino) phenylarsonous acid (111In-GSAO). Thereafter, hearts were explanted for ex vivo imaging, γ-counting, and histopathological characterization. RESULTS: Myocardial damage was visualized by micro-SPECT/CT imaging. Quantitative GSAO uptake (expressed as percent injected dose per gram, %ID/g) in the area at risk was lower in minocycline-treated animals than that in saline-treated control animals (0.32 ± 0.13% vs 0.48 ± 0.15%, P = 0.04). TUNEL staining confirmed the reduction of cell death in minocycline-treated animals. CONCLUSIONS: This study demonstrates cardioprotection by minocycline in a clinically translatable protocol.
BACKGROUND: Preclinical studies indicate that minocycline protects against myocardial ischemia/reperfusion injury. In these studies, minocycline was administered before ischemia, which can rarely occur in clinical practice. The current study aimed to evaluate cardioprotection by minocycline treatment upon reperfusion. METHODS:Rabbits were subjected to myocardial ischemia/reperfusion injury and received either intravenous minocycline (n = 8) or saline (n = 8) upon reperfusion. Cardiac cell death was assessed by in vivo micro-SPECT/CT after injection of Indium-111-labeled 4-(N-(S-glutathionylacetyl)amino) phenylarsonous acid (111In-GSAO). Thereafter, hearts were explanted for ex vivo imaging, γ-counting, and histopathological characterization. RESULTS:Myocardial damage was visualized by micro-SPECT/CT imaging. Quantitative GSAO uptake (expressed as percent injected dose per gram, %ID/g) in the area at risk was lower in minocycline-treated animals than that in saline-treated control animals (0.32 ± 0.13% vs 0.48 ± 0.15%, P = 0.04). TUNEL staining confirmed the reduction of cell death in minocycline-treated animals. CONCLUSIONS: This study demonstrates cardioprotection by minocycline in a clinically translatable protocol.
Authors: Hendrikus H Boersma; Bas L J H Kietselaer; Leo M L Stolk; Abdelkader Bennaghmouch; Leonard Hofstra; Jagat Narula; Guido A K Heidendal; Chris P M Reutelingsperger Journal: J Nucl Med Date: 2005-12 Impact factor: 10.057
Authors: Heidi Kenis; Harmen Reinier Zandbergen; Leonard Hofstra; Artiom D Petrov; Ewald A Dumont; Francis D Blankenberg; Nezam Haider; Nicole Bitsch; Marion Gijbels; Johan W H Verjans; Navneet Narula; Jagat Narula; Chris P M Reutelingsperger Journal: J Nucl Med Date: 2010-02 Impact factor: 10.057
Authors: Tiziano M Scarabelli; Anastasis Stephanou; Evasio Pasini; Gianluca Gitti; Paul Townsend; Kevin Lawrence; Carol Chen-Scarabelli; Louis Saravolatz; David Latchman; Richard Knight; Julius Gardin Journal: J Am Coll Cardiol Date: 2004-03-03 Impact factor: 24.094
Authors: B-W Xie; D Park; E R Van Beek; V Blankevoort; Y Orabi; I Que; E L Kaijzel; A Chan; P J Hogg; C W G M Löwik Journal: Cell Death Dis Date: 2013-01-24 Impact factor: 8.469