Effects of mexidol in patients with chronic brain ischemia and chronic heart failure (II-III functional class)

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AIM

To study the effect of mexidol on N-terminal pro B-type natriuretic peptide (NT-proBNP), markers of oxidative stress, inflammatory reaction and endothelial dysfunction in patients with chronic brain ischemia and chronic heart failure II-III NYHA functional class while 13 weeks of sequential intravenous and oral therapy with mexidol and standard therapy.

MATERIAL AND METHODS

Study included 44 patients with chronic brain ischemia and chronic heart failure II-III NYHA functional class with ejection fraction less 50%. Mean age: 65.5±11.8 years, 75% men. 21 patients of group mexidol plus standard therapy of chronic heart failure received mexidol at a dose of 1000 mg/day by intravenous infusion for 7 days followed by oral doses of 250 mg three times a day for twelve weeks, 23 patients received standard therapy. 34 patients completed the trial, in 10 patient the final visit was performed as telephone call due to epidemiologic situation. Concentration of N-terminal pro B-type natriuretic peptide (NT-proBNP), markers of oxidative stress (malonic dialdehyde (MDA), superoxide dismutase (SOD)), inflammatory reaction (C-reactive protein (CRP), tumor necrosis factor α (TNFα)), homocysteine and cystatin C were examined in blinded manner in all patients initially, on day 7 and week 13.

RESULTS

Statistically significant more prominent decrease of NT-proBNP, MDA, CRP and TNFα and increase of SOD by day 7 and week 13 were observed in patients treated with mexidol along with standard therapy in comparison with group treated with standard therapy.

CONCLUSION

Mexidol added to standard therapy of patients with chronic brain ischemia and chronic heart failure II-III functional class decreases concentration of NT-proBNP, has proven antioxidant activity, decreases the degree of inflammatory reaction, slows down the increase of homocysteine, does not influence the kidney function (by measurement of cystatin C).

Keywords:

chronic brain ischemia

heart failure

oxidative stress

antioxidants

N-terminal pro B-type natriuretic peptide (NT-proBNP)

malonic dialdehyde

superoxide dismutase

CRP

TNFα

ethyl-methyl-hydroxipyridin succinate

mexidol

Authors:

Shchulkin A.V.

Pavlov Ryazan State Medical University

Kazakhmedov E.R.

Peoples’ Friendship University of Russia named after Patris Lumumber

ORCID: 0000-0002-6274-8933

Galochkin S.A.

Peoples’ Friendship University of Russia named after Patris Lumumber

ORCID: 0000-0001-7370-8606

Tolkacheva V.V.

Peoples’ Friendship University of Russia named after Patris Lumumber

ORCID: 0000-0001-6847-8797

Kobalava Z.D.

Peoples’ Friendship University of Russia named after Patris Lumumber

ORCID: 0000-0002-5873-1768

Received:

21.08.2020

Accepted:

10.09.2020

List of references:

Katz SD, Hryniewicz K, Hriljac I, et al. Vascular endothelial dysfunction and mortality risk in patients with chronic heart failure. Circulation. 2005;111:310-314. https://doi.org/10.1161/01.cir.0000153349.77489
Higashi Y, Noma K, Yoshizumi M, et al. Endothelial function and oxidative stress in cardiovascular diseases. Circulation J. 2009; 3:411-415. https://doi.org/10.1253/circj.cj-08-1102
Romuk E, Wojciechowska C, Jacheć W, et al. Comparison of Oxidative Stress Parameters in Heart Failure Patients Depending on Ischaemic or Nonischaemic Aetiology. Oxidative Medicine and Cellular Longevity. 2019;Article ID 7156038. https://doi.org/10.1155/2019/7156038
Guzik TJ, Harrison DG. Vascular NADPH oxidases as drug targets for novel antioxidant strategies. Drug Discovery Today. 2006;11-12:524-526. https://doi.org/10.1016/j.drudis.2006.04.003
Drapkina OM, Palatkina LO. New emphases on the study of the pathogenesis of chronic heart failure with preserved ejection fraction: focus on inflammatory markers. Rational Pharmacotherapy in Cardiology. 2014;10(3):317-321. (In Russ.). https://doi.org/10.20996/1819-6446-2014-10-3-317-321
Petersen JW, Felker GM. Inflammatory Biomarkers in Heart Failure. Congestive Heart Failure. 2006;12(6):324-328. https://doi.org/10.1111/j.1527-5299.2006.05595
Palatkina LO, Korneeva ON, Drapkina OM. Oxidative stress, its role in the pathogenesis of chronic heart failure, and potential methods of correction. Cardiovascular Therapy and Prevention. 2012;11(6):91-94. (In Russ.). https://doi.org/10.15829/1728-8800-2012-6-91-94
Arutyunov AG, Dragunov DO, Arutyunov GP, Rylova AK, Sokolova AV, Rylova NV. Prognostically significant clinical phenotypes of patients with circulatory decompensation in the Russian Federation. Russian Heart Failure Journal. 2015;16(5):270-278. (In Russ.).
D’Elia E, Vaduganathan M, Gori M, Gavazzi A. Role of biomarkers in cardiac structure phenotyping in heart failure with pre-served ejection fraction: critical appraisal and practical use. Eur J Heart Fail. 2015;17(12):1231-1239. https://doi.org/10.1002/ejhf.43
Voronina TA, Ivanova EA. Combined administration of mexidol with known medicines. Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova. 2019;119(4):115-124. (In Russ.). https://doi.org/10.17116/jnevro2019119041115
Statsenko ME, Evtereva ED, Turkina SV, et al. New possibilities of mexicor in the treatment of chronic heart failure in patients with metabolic syndrome. Russian Journal of Cardiology 2010;6(86):28-33. (In Russ.). https://doi.org/10.15829/1560-4071-2010-6-28-33
Sidorenko GI, Komissarova SM, Zolotukhina SF, Petrovskaya ME. The use of ethylmethylhydoxypyridine succinate in the treatment of patients with heart failure. Kardiologya. 2011;6:44-48. (In Russ.).
Kostyuk VA, Potapovich AI, Kovaleva ZhV. Prostoj i chuvstvitel’nyj metod opredeleniya aktivnosti superoksiddismutazy, osnovannyj na reaktsii okisleniya kvertsitina. Voprosy meditsinskoj khimii. 1990;36(2):88-91. (In Russ.).
Polunina EA, Voronina LP, Popov EA, Belyakova IS, Polunina OS, Tarasochkina DS. Prognostic algorithms for the progression of chronic heart failure depending on the clinical phenotype. Cardiovascular Therapy and Prevention. 2019;18(3):41-47. (In Russ.). https://doi.org/10.15829/1728-8800-2019-3-41-47
Shchulkin AV. A modern concept of antihypoxic and antioxidant effects of mexidol. Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova. 2018;12(2):87-93. (In Russ.). https://doi.org/10.17116/jnevro201811812287
Klinicheskie rekomendatsii OSSN — RKO — RNMOT. Serdechnaya nedostatochnost’: khronicheskaya (KhSN) i ostraya dekompensirovannaya (ODSN). Diagnostika, profilaktika i lechenie. 2018. (In Russ.). https://doi.org/10.18087/cardio.2475
Ferreira JP, Duarte K, Graves TL, Zile MR, Abraham WT, Weaver FA, et al. Natriuretic Peptides, 6-Min Walk Test, and Quality-of-Life Questionnaires as Clinically Meaningful Endpoints in HF Trials. J Am Coll Cardiol. 2016;68(24):2690-2707. https://doi.org/10.1016/j.jacc.2016.09.936
Shchulkin AV. Vliyanie meksidola na razvitie fenomena eksajtotoksichnosti nejronov in vitro. Zhurnal nevrologii i psihiatrii imeni S.S. Korsakova. 2012;112(2):35-39. (In Russ.).
D’Oria R, Schipani R, Leonardini A, Natalicchio A, Perrini S, Cignarelli A, Laviola L, Giorgino F. The role of oxidative stress in cardiac disease: from physiological response to injury factor. Oxidative Medicine and Cellular longevity. 2020. https://doi.org/10.1155/2020/5732956
Price BR, Wilcock DM and Weekman EM Front. Aging Neurosci. 2018;10(10):350. https://doi.org/10.3389/fnagi.2018.00350
Naruszewicz M, Jankowska EA, Zymlinski R, Bukowska H, Millo B, Banasiak W, Ponikowski P. Hyperhomocysteinemia in patients with symptomatic chronic heart failure: Prevalence and prognostic importance — pilot study. Atherosclerosis. 2007;194:408-414. https://doi.org/10.1016/j.atherosclerosis.2006.08.014
Kasperczyk S, Dobrakowski M, Kasperczyk A, et al. Effect of N-acetylcysteine administration on homocysteine level, oxidative damage to proteins, and levels of iron (Fe) and Fe-related proteins in lead-exposed workers. Toxicol Ind Health. 2016;32(9):1607-1618. https://doi.org/10.1177/0748233715571152
Yin W-H, Chen J-W, Jen H-L, Chiang M-C, Huang W-P, Feng A-N, Lin S-J. Independent prognostic value of elevated high-sensitivity C-reactive protein in chronic heart failure. American Heart Journal. 2004;147(5):931-938. https://doi.org/10.1016/j.ahj.2003.11.021
Sato Y, Takatsu Y, Kataoka K, Yamada T, Taniguchi R, Sasayama S, Matsumori A. Serial circulating concentra- tions of C-reactive protein, interleukin (IL)-4, and IL-6 in patients with acute left heart decompensation. Clinical Cardiology. 1999;22:811-813. https://doi.org/10.1002/clc.4960221211
Yamauchi-Takihara K, Ihara Y, Ogata A, Yoshizaki K, Azuma J, Kishimoto T. Hypoxic stress induces cardiac myocyte-derived interleukin-6. Circulation. 1995;91:1520-1524. https://doi.org/10.1161/01.CIR.91.5.1520
Ferrari R. The role of TNF in cardiovascular disease. Pharmacological Research. 1999;40(2):97-105. https://doi.org/10.1006/phrs.1998.0463
Kirova YuI, Shakova FM, Germanova EL, Romanova GA, Voronina TA. Vliyanie Meksidola na tserebral’nyj mitokhondriogenez v molodom vozraste i pri starenii. Zhurnal nevrologii i psihiatrii imeni S.S. Korsakova. 2020;120(1):62-69. (In Russ.). https://doi.org/10.17116/jnevro202012001162
Ferguson TW, Komenda P, Tangri N. Cystatin C as a Biomarker for Estimating Glomerular Filtration Rate. Curr Opin Nephrol Hypertens. 2015;24(3):295-300. https://doi.org/10.1097/MNH.0000000000000115

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