Prevention of cardiac reperfusion injury following global ischemia by a monoclonal antibody,R2-1A6 |
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| Affiliation: | 1. 2nd Department of Surgery, Sapporo Medical University School of Medicine, Minami-1, Nishi-17, Chuo-ku, Japan;2. Section of Immunopathogenesis, Institute of Immunological Science, Hokkaido University, Kita-15, Nishi-7, Kita-ku, Sapporo, 060, Japan;1. Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa;2. Cardiometabolics Unit, Zena and Michael A Wiener Cardiovascular Institute, Marie-Josee and Henry R. Kravis Center for Cardiovascular Health, Icahn School of Medicine at Mount Sinai, New York, New York, USA;3. Department of Vascular Medicine, University of Amsterdam, Amsterdam, The Netherlands;4. Department of Internal Medicine and Surgery, Federico II University, Naples, Italy;5. Knight Cardiovascular Institute and Division of Endocrinology, Diabetes and Clinical Nutrition, Oregon Health & Science University, Portland, Oregon, USA;6. Division of Cardiovascular Medicine, Department of Medicine, Osaka University Graduate School of Medicine, Osaka, Japan;7. Amsterdam Cardiovascular Sciences, Amsterdam, The Netherlands;8. Regeneron Pharmaceuticals, Inc, Tarrytown, New York, USA;9. Clinical Lipidology and Rare Lipid Disorders Unit, Department of Medicine, Université de Montréal Community Gene Medicine Center, Lipid Clinic Chicoutimi Hospital and ECOGENE-21 Clinical and Translational Research Center, Chicoutimi, Quebec, Canada;1. Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA;2. Department of Cardiology, Hartford Hospital, Hartford, CT;1. Carbohydrate and Lipid Metabolism Research Unit, Faculty of Health Sciences, University of Witwatersrand, Johannesburg, South Africa;2. Amgen Inc, One Amgen Center Drive, Thousand Oaks, CA, USA;3. Division of Lipidology, Department of Medicine, University of Cape Town, UCT Faculty Health Sciences, Cape Town, South Africa;4. Vascular Medicine, Academic Medical Centre, Amsterdam, Netherlands;5. Metabolic and Atherosclerosis Research Center, Cincinnati, OH, USA;1. Division of Vascular Surgery, Department of Surgery, Stanford University School of Medicine, Stanford, California, USA;2. Department of Surgery, University of Hawaii, Honolulu, Hawaii, USA;3. Division of Pediatric Critical Care Medicine, Department of Pediatrics, Stanford University School of Medicine, Stanford, California, USA;4. Division of Nephrology, Department of Medicine, Stanford University School of Medicine, Stanford, California, USA;1. Université Paris Cité, Paris, France;2. IQVIA, Tour D2, 17 bis, place des Reflets, 92099 La Défense cedex, France;3. Service de médecine interne, hôpital Franco-Britannique, 4, rue Kléber, 92300 Levallois-Perret, France;1. Centre for Inherited Cardiovascular Disease, IRCCS Foundation Policlinico San Matteo, Pavia, Italy;2. Department of Internal Medicine, University Hospital Würzburg, and Comprehensive Heart Failure Center, University of Würzburg, Würzburg, Germany;3. Lillehei Heart Institute and Division of Cardiology, Department of Medicine, University of Minnesota, Minneapolis, Minnesota |
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| Abstract: | The effect of R2-1A6 monoclonal antibody on the reperfusion injury of heterotopically transplanted rat cardiac tissues after global ischemia was studied. Histological, functional as well as myocardial energy status were evaluated in control and R2-1A6-treated rats. The strong binding of neutrophils to cardiac endothelial cell surface and strong tissue edema were present at 10 min after the initiation of reperfusion and subsequently interstitial hemmorhage and myocardial degeneration were present in the control group. The mean survival date of grafted hearts was about 7.7 days in the control group. In contrast, the significantly less severe binding of neutrophils to endothelial cells, tissue edema, interstitial hemorrhage, and myocardial degeneration were present in R2-1A6-treated rats. All grafted hearts survived up to 14 days in R2-1A6-treated group. Myocardial ATP content decreased from preischemic value of about 4 μmol/g to post-ischemic value of 0.57 μmol/g. After reperfusion of ischemic hearts, myocardial ATP values remained to be a range of 1.27–1.03 μmol/g in control group. However, myocardial ATP values recovered up to 2.28 μmol/g in R2-1A6-treated group. Thus, these experiments indicated that neutrophil adherence to endothelial cells is a critical early event in the process leading to post-ischemic reperfusion injury in global ischemia and the R2-1A6 treatment resulted in significant protection against cardiac reperfusion injury following global ischemia. |
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