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Benefit of a single intravenous injection of the new drug of ubiquinol in the development of systolic and diastolic dysfunction in rats with myocardial infarction

DOI 10.18127/j20700997-201804-06

Keywords:

O.Yu. Kulyak - Post-graduate Student, Faculty of Medicine, Lomonosov Moscow State University
E-mail: Kulyak-Olesya@mail.ru
E.A. Gorodetskaya - Ph.D. (Biol.), Associate Professor, Faculty of Medicine, Lomonosov Moscow State University
E-mail: gorodeag@mail.ru
M.M. Artemieva - Ph.D. (Med.), Research Scientist, Faculty of Biology, Lomonosov Moscow State University
E-mail: marinka.artemieva@gmail.com
E.I. Kalenikova - Ph.D. (Pharm.), Associate Professor, Faculty of Medicine, Lomonosov Moscow State University
E-mail: eikaleni@yandex.ru
O.S. Medvedev - Dr.Sc. (Med.), Professor, Head of Department, Faculty of Medicine, Lomonosov Moscow State University
E-mail: oleg.omedvedev@gmail.com


Introduction: Experimental and clinical studies demonstrate the prospects of using the reduced form of coenzyme Q10 (ubiquinol) in the treatment of various pathological conditions associated with redox imbalance.
Purpose of the research was to examine the cardioprotective effectiveness of intravenously administrated ubiquinol based on the morphofunctional characteristics of the heart in a model of myocardial infarction in rats.
Methods: Wistar rats were used (n = 30, m = 300-350 g). Animals were anesthetized with thiopental sodium (intraperito-neally, 45 mg/kg). After thoracotomy, a ligature was applied to the anterior descending branch of the left coronary artery (Proline 6/0, Ethicon, USA). 10 minutes after occlusion of the coronary artery, 1% ubiquinol solution was injected intrave-nously (patent № RU2635993-C1, ZAO NPO DOM PHARMACY") at a dose of 10 mg/kg (group "IM + CoQ10H2", n = 8) or physiological saline at a dose of 1 ml/kg (group" IM ", n = 6). False saline was administered to the falsely operated animals (group "LO", n = 9). Morphofunctional heart parameters were assessed on day 21 after the operation.
Results: In animal groups "IM" and "IM + CoQ10H2", connective tissue aneurysms as well as infarct scars located in the LV myocardium were formed in the blood supply pool of the occluded artery. The administration of ubiquinol significantly limited the size of the aneurysm: 2.1 ± 2.0% and 31.6 ± 12.2% in the "IM + CoQ10H2" and "IM" groups, respectively
(p < 0.05). The size of postinfarction scars in these groups did not differ (14.3 ± 6.2% vs 13.2 ± 9.5%). LV hypertrophy was developed in the group of animals "IM" on the 21st day: the thickness of the interventricular septum was 2.71 ± 0.14 mm, which is statistically significantly higher (p < 0.01) than in the "LO" group (2.48 ± 0.19 mm). The animals of the group "IM + CoQ10H2" showed no signs of LV hypertrophy: the thickness of the interventricular septum (2.55 ± 0.16 mm) did not differ from the "LO" group and was less than in the "IM" group (p < 0.05). The occlusion of the coronary arteries led to the development of left ventricular heart failure: ejection fraction was reduced by 38%, impact volume was reduced by 27%, cardiac output was reduced by 30%, end-systolic pressure was reduced by 20%, and end-systolic volume increased by 44% and end-diastolic volume was increased by 23% relative to the group of animals "LO" (with confidence p < 0.05 for all indi-cators). Intravenous administration of the drug has led to the prevention of reduction in cardiac output and stroke volume, limiting the reduction of the ejection fraction (11%), end-systolic pressure (17%), and a smaller increase in end-systolic (20%) and end-diastolic (16%) volume.
Conclusion: A single intravenous injection of an innovative drug form of the ubiquinol at a dose of 10 mg/kg in the first minutes after the onset of myocardial ischemia limits the area of myocardial damage, prevents the development of LV hypertrophy, and limits the development of systolic and diastolic myocardial dysfunction. The obtained results confirm the cardioprotective effectiveness of the innovative drug ubiquinol for intravenous administration in the urgent therapy of car-diovascular diseases.

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