Efficacy of Empagliflozin in the Treatment of Experimental Myocardial Infarction
-
Published:2023-11-07
Issue:
Volume:
Page:
-
ISSN:2658-5049
-
Container-title:Drug development & registration
-
language:
-
Short-container-title:Razrabotka i registraciâ lekarstvennyh sredstv
Author:
Ivkin D. Yu.1ORCID, Krasnova M. V.1ORCID, Okovity S. V.1ORCID, Karpov A. A.2ORCID, Kulikov A. A.3ORCID, Yeletskaya E. I.1ORCID
Affiliation:
1. Saint-Petersburg State Chemical and Pharmaceutical University 2. Almazov National Medical Research Centre 3. FSBEI HE I.P. Pavlov SPbSMU MOH Russia
Abstract
Introduction. With the emergence of empagliflozin in the pharmaceutical market, there has been an increase in publications on the primary and secondary pharmacodynamics of the drug, and the list of potential indications for the use of this sodium-glucose co-transporter inhibitor is increasing. Hypotheses about pharmacological effects and mechanisms of their implementation are tested both in large-scale clinical studies and in animal experiments.Aim. The purpose of this work was to study the effectiveness of empagliflozin by echocardiographic, histological and molecular biological analyses at the three most significant points of the dynamic transition from acute myocardial infarction to post-infarction chronic heart failure in laboratory male rats.Materials and methods. The experiment was performed on 60 male outbred rats. Myocardial infarction was modeled in narcotic animals by permanent ligation of the left coronary artery. Based on echocardiographic (EchoCG) study data, animals were randomized to two groups: control infarction: untreated pathology group treated with placebo and pathology group treated with empagliflozin 1 mg/kg per os intragastric daily from the first day of the experiment. At 10, 20 and 30 days after the operation, the animals were also subjected to EchoCG testing, and a group of 10 animals from each group were euthanized for histological examination and molecular analysis.Results and discussion. Empagliflozin use in animals after myocardial infarction modeling contributed to a significant increase in myocardial performance on days 10, 20 and 30, reaching a maximum on day 20 (47.58 ± 1.87 %). The drug promotes long-term preservation of the area of damage to the heart muscle with early formation of mature connective tissue, and also increases myocardial resistance to hypoxia by increasing the amount of HIF-1.Conclusion. Based on the studies carried out, it can be concluded that it is possible to use the sodium-glucose cotransporter type 2 empagliflozin in the formation of post-infarction chronic heart failure in the conditions of normoglycemia.
Publisher
Center of Pharmaceutical Analytics Ltd
Subject
Drug Discovery,Pharmaceutical Science
Reference14 articles.
1. Shalnova S. A., Drapkina O. M., Kutsenko V. A., Kapustina A. V., Muromtseva G. A., Yarovaya E. B., Balanova Yu. A., Evstifeeva S. E., Imaeva A. E., Shlyakhto E. V., Boytsov S. A., Astakhova Z. T., Barbarash O. L., Belova O. A., Grinshtein Yu. I., Efanov A. Yu., Kalachikova O. N., Kulakova N. V., Nedogoda S. V., Rotar O. P., Trubacheva I. A., Chernykh on behalf of the ESSE-RF study participants. T.M. Myocardial infarction in the population of some Russian regions and its prognostic value. Russian Journal of Cardiology. 2022;27(6):4952. (In Russ.) DOI: 10.15829/1560-4071-2022-4952. 2. Krasnova M., Kulikov A., Okovityi S., Ivkin D., Karpov A., Kaschina E., Smirnov A. Comparative efficacy of empagliflozin and drugs of baseline therapy in post-infarct heart failure in normoglycemic rats. Naunyn Schmiedebergs Arch Pharmacol. 2020;393(9):1649–1658. DOI: 10.1007/s00210-020-01873-7. 3. Damman K., Beusekamp J. C., Boorsma E. M., Swart H. P., Smilde T. D. J., Elvan A., van Eck J. W. M., Heerspink H. J. L., Voors A. A. Randomized, double-blind, placebo-controlled, multicentre pilot study on the effects of empagliflozin on clinical outcomes in patients with acute decompensated heart failure (EMPA-RESPONSE-AHF). Eur. J. Heart Fail. 2020;22:713–722. 4. Janbandhu V., Tallapragada V., Patrick R., Li Y., Abeygunawardena D., Humphreys D. T., Martin E. M. M. A., Ward A. O., Contreras O., Farbehi N., Yao E., Du J., Dunwoodie S. L., Bursac N., Harvey R. P. Hif-1a suppresses ROS-induced proliferation of cardiac fibroblasts following myocardial infarction. Cell Stem Cell. 2022;29(2):281–297. DOI: 10.1016/j.stem.2021.10.009. 5. Qi B., Song L., Hu L., Guo D., Ren G., Peng T., Liu M., Fang Y., Li C., Zhang M., Li Y. Cardiac-specific overexpression of Ndufs1 ameliorates cardiac dysfunction after myocardial infarction by alleviating mitochondrial dysfunction and apoptosis. Experimental & Molecular Medicine. 2022;54:946–960. DOI: 10.1038/s12276-022-00800-5.
|
|