Comparative Efficacy of Levosimendan, Ramipril, and Sacubitril/ Valsartan in Isoproterenol-induced Experimental Heart Failure: A Hemodynamic and Molecular Approach.

IF 2.4 4区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Current molecular pharmacology Pub Date : 2023-01-01 DOI:10.2174/1874467215666220919104526

Md Sayeed Akhtar, Md Quamrul Hassan, Obaid Afzal, Abdulmalik S A Altamimi, Mohd Zaheen Hassan, Arun Kumar, Asif Ansari Shaik Mohammad, Fauzia Tabassum

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Abstract

Objective: Cardiac ischemia-related myocardial damage has been considered a major reason for heart failure. We aimed to investigate the role of levosimendan (LEVO) in comparison to ramipril and sacubitril/valsartan (Sac/Val) in preventing damage associated with isoproterenol (ISO) induced myocardial infarction.

Methods: Myocardial infarction was induced by injecting subcutaneous isoproterenol (5 mg/kg once for 7 consecutive days) to establish an experimental heart failure model. Simultaneously, LEVO (1 mg/kg/day), ramipril (3mg/kg/day) and Sac/Val (68 mg/kg/day) suspension were administered orally for four weeks.

Results: We observed a significant correlation between ISO-induced ischemia with cardiac remodeling and alterations in myocardial architecture. LEVO, ramipril, and Sac/Val significantly prevented lipid peroxidation and damaged antioxidant enzymes like superoxide dismutase, catalase, glutathione and thioredoxin reductase. We also observed their ameliorative effects in myocardium's cardiac hypertrophy, evidenced by reduced heart weight to body weight ratio and transforming growth factor β related collagen deposition. LEVO, ramipril, and Sac/Val also maintained cardiac biomarkers like lactate dehydrogenase, creatine kinase-MB, brain natriuretic peptide and cardiac Troponin-I, indicating reduced myocardial damage that was further demonstrated by histopathological examination. Decreased sarcoplasmic endoplasmic reticulum Ca2+ATPase2a and sodium-calcium exchanger-1 protein depletion after LEVO, ramipril, and Sac/Val administration indicated improved Ca2+ homeostasis during myocardial contractility.

Conclusion: Our findings suggest that LEVO has comparable effects to ramipril, and Sac/Val in preventing myocardial damage via balancing oxidant-antioxidant system, decreased collagen deposition, reduced myocardial stress as well as improved Ca2+ homeostasis during myocardial contractility.

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左西孟旦、雷米普利和苏比里尔/缬沙坦治疗异丙肾上腺素诱导的实验性心力衰竭的比较疗效:血液动力学和分子方法。

目的:心肌缺血相关的心肌损伤一直被认为是心衰的主要原因。我们的目的是研究左西孟旦(LEVO)与雷米普利和苏比里尔/缬沙坦(Sac/Val)在预防异丙肾上腺素(ISO)诱导的心肌梗死相关损伤方面的作用。方法:采用异丙肾上腺素皮下注射(5 mg/kg 1次，连续7 d)诱导心肌梗死，建立实验性心力衰竭模型。同时口服LEVO (1 mg/kg/day)、雷米普利(3mg/kg/day)和Sac/Val (68 mg/kg/day)混悬液4周。结果:我们观察到iso诱导的心肌缺血与心肌重构和心肌结构改变有显著的相关性。LEVO、雷米普利和Sac/Val可显著防止脂质过氧化，并破坏超氧化物歧化酶、过氧化氢酶、谷胱甘肽和硫氧还蛋白还原酶等抗氧化酶。我们还观察到它们对心肌肥厚的改善作用，证明了心脏重量与体重比的降低和转化生长因子β相关的胶原沉积。LEVO、雷米普利和Sac/Val还维持了乳酸脱氢酶、肌酸激酶mb、脑利钠肽和心肌肌钙蛋白- 1等心脏生物标志物，表明心肌损伤减轻，组织病理学检查进一步证实了这一点。在LEVO、雷米普利和Sac/Val给药后，肌浆内质网Ca2+ATPase2a和钠钙交换器-1蛋白的减少表明心肌收缩期间Ca2+稳态得到改善。结论:我们的研究结果表明，LEVO在通过平衡氧化-抗氧化系统、减少胶原沉积、减轻心肌应激以及改善心肌收缩期间Ca2+稳态来预防心肌损伤方面具有与雷米普利和Sac/Val相当的作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Current molecular pharmacology Pharmacology, Toxicology and Pharmaceutics-Drug Discovery

CiteScore

4.90

自引率

3.70%

发文量

112

期刊介绍： Current Molecular Pharmacology aims to publish the latest developments in cellular and molecular pharmacology with a major emphasis on the mechanism of action of novel drugs under development, innovative pharmacological technologies, cell signaling, transduction pathway analysis, genomics, proteomics, and metabonomics applications to drug action. An additional focus will be the way in which normal biological function is illuminated by knowledge of the action of drugs at the cellular and molecular level. The journal publishes full-length/mini reviews, original research articles and thematic issues on molecular pharmacology. Current Molecular Pharmacology is an essential journal for every scientist who is involved in drug design and discovery, target identification, target validation, preclinical and clinical development of drugs therapeutically useful in human disease.