Protection of ischemic myocardium by exogenous phosphocreatine (neoton): pharmacokinetics of phosphocreatine, reduction of infarct size, stabilization of sarcolemma of ischemic cardiomyocytes, and antithrombotic action |
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| Authors: | V G Sharov N I Afonskaya M Y Ruda N M Cherpachenko Markosyan" target="_blank">R A Pozin EYaMarkosyan I I Shepeleva M B Samarenko V A Saks |
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| Institution: | 1. Faculty of Civil Engineering, University of Tehran, Tehran, Iran;2. Department of Civil Engineering, Faculty of Engineering, Lorestan University, Lorestan, Iran;3. Department of Civil Engineering, Lakehead University, Thunder Bay, Canada;4. Disaster Preparedness & Prevention Centre (DPPC), Malaysia-Japan International Institute of Technology (MJIIT), Universiti Teknologi Malaysia, Kuala Lumpur, Malaysia;1. P.P.Shirshov Institute of Oceanology of Russian Academy of Sciences, Atlantic Branch, Laboratory for Marine Physics, prospect Mira, 1, Kaliningrad, 236022, Russia;2. P.P.Shirshov Institute of Oceanology of Russian Academy of Sciences, Sea currents Laboratory, Nakhimovski prospect, 36, Moscow, 117997, Russia;1. Division of Nephrology-Hypertension, University of California San Diego, San Diego, CA;2. Veterans Affairs San Diego Healthcare System, San Diego, CA;3. Kidney Health Research Collaborative, San Francisco Veterans Affairs Health Care System and University of California San Francisco, San Francisco, CA;4. University of Washington, Seattle, WA;5. Division of Public Health Sciences, Department of Biostatistics and Data Science, Wake Forest School of Medicine, Winston-Salem, NC;6. Division of Nephrology and Hypertension, University of Utah, Salt Lake City, UT;7. Division of Nephrology, UCLA David Geffen School of Medicine, Los Angeles, CA;1. Division of Infection, Immunity and Respiratory Medicine, University of Manchester, Manchester, UK;2. University Hospital South Manchester NHS Foundation Trust, Manchester, UK;3. Research Centre on Asthma and COPD, University of Ferrara, Ferrara, Italy;4. Department of Clinical and Experimental Medicine, University of Parma, Parma, Italy;5. Pulmonology Department No 2, Kharkiv City Clinical Hospital No 13, Kharkiv, Ukraine;6. Global Clinical Development, Chiesi Farmaceutici SpA, Parma, Italy;7. Global Clinical Development, Chiesi SAS, Courbevoie, France;8. Medicines Evaluation Unit, Manchester, UK |
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| Abstract: | The effect of exogenous phosphocreatine on ischemic myocardium was studied in experimental infarction in rabbits and in total ischemia of pig heart tissue (in vitro). It is shown that single dose administration of phosphocreatine is followed by its rapid clearance from blood plasma (with a half lifetime of 4-6 min), but constantly high plasma concentration of phosphocreatine can be maintained by its intravenous infusion. When administered by this method into rabbits during experimental myocardial infarction, phosphocreatine reduces by 40% the size of the necrotic zone. Morphological electron microscopic studies using a lanthanum tracer method showed significant protection of the sarcolemma of cardiomyocytes in the perinecrotic zone by phosphocreatine. In vitro studies on the model of total ischemia also showed significant protection of cardiac sarcolemma from irreversible ischemic injury and reduction in the rate of high-energy phosphate depletion in the presence of phosphocreatine in the extracellular space. Additionally, it is demonstrated that creatine kinase released during myocardial infarction into the blood flow and exogenous phosphocreatine administered intravenously may significantly inhibit platelet aggregation by rapid removal of ADP, and thus potentially improve microcirculation during myocardial infarction. |
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