Protective effects of meldonium in experimental models of cardiovascular complications with a potential application in COVID‐19
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Date
2022-01-01
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Abstract
Right ventricular (RV) and left ventricular (LV) dysfunction is common in a significant number of hospitalized coronavirus disease 2019 (COVID‐19) patients. This study was conducted to assess whether the improved mitochondrial bioenergetics by cardiometabolic drug meldonium can attenuate the development of ventricular dysfunction in experimental RV and LV dysfunction models, which resemble ventricular dysfunction in COVID‐19 patients. Effects of meldonium were assessed in rats with pulmonary hypertension‐induced RV failure and in mice with inflammation-induced LV dysfunction. Rats with RV failure showed decreased RV fractional area change (RVFAC) and hypertrophy. Treatment with meldonium attenuated the development of RV hyper-trophy and increased RVFAC by 50%. Mice with inflammation‐induced LV dysfunction had decreased LV ejection fraction (LVEF) by 30%. Treatment with meldonium prevented the decrease in LVEF. A decrease in the mitochondrial fatty acid oxidation with a concomitant increase in pyruvate metabolism was noted in the cardiac fibers of the rats and mice with RV and LV failure, respectively. Meldonium treatment in both models restored mitochondrial bioenergetics. The results show that meldonium treatment prevents the development of RV and LV systolic dysfunction by enhancing mitochondrial function in experimental models of ventricular dysfunction that resembles cardiovascular complications in COVID‐19 patients.
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Funding Information: Funding: This study was supported by the Latvian State Research Program project VPP‐COVID‐ 2020/1‐0014 ʺTowards new therapeutic and prophylactic treatments against Covid‐19 and corona‐ virusesʺ. Dana Kigitovica received Doctoral study grant from Riga Stradins University. Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.
Keywords
COVID‐19 cardiovascular complications, Left ventricular dysfunction, Meldonium, Mitochondria, Right ventricular dysfunction, 1.4 Chemical sciences, 1.6 Biological sciences, 3.1 Basic medicine, 1.1. Scientific article indexed in Web of Science and/or Scopus database, Catalysis, Molecular Biology, Spectroscopy, Computer Science Applications, Physical and Theoretical Chemistry, Organic Chemistry, Inorganic Chemistry
Citation
Vilskersts, R, Kigitovica, D, Korzh, S, Videja, M, Vilks, K, Cirule, H, Skride, A, Makrecka‐Kuka, M, Liepinsh, E & Dambrova, M 2022, 'Protective effects of meldonium in experimental models of cardiovascular complications with a potential application in COVID‐19', International Journal of Molecular Sciences, vol. 23, no. 1, 45. https://doi.org/10.3390/ijms23010045