TY - JOUR
T1 - Protective effects of meldonium in experimental models of cardiovascular complications with a potential application in COVID‐19
AU - Vilskersts, Reinis
AU - Kigitovica, Dana
AU - Korzh, Stanislava
AU - Videja, Melita
AU - Vilks, Karlis
AU - Cirule, Helena
AU - Skride, Andris
AU - Makrecka‐Kuka, Marina
AU - Liepinsh, Edgars
AU - Dambrova, Maija
N1 - 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.
PY - 2022/1/1
Y1 - 2022/1/1
N2 - 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.
AB - 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.
KW - COVID‐19 cardiovascular complications
KW - Left ventricular dysfunction
KW - Meldonium
KW - Mitochondria
KW - Right ventricular dysfunction
UR - http://www.scopus.com/inward/record.url?scp=85121355885&partnerID=8YFLogxK
UR - https://www-webofscience-com.db.rsu.lv/wos/alldb/full-record/WOS:000759180900001
U2 - 10.3390/ijms23010045
DO - 10.3390/ijms23010045
M3 - Article
AN - SCOPUS:85121355885
SN - 1661-6596
VL - 23
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
IS - 1
M1 - 45
ER -