Influence of trimetazidine and ranolazine on endothelial function in patients with ischemic heart disease

Likozar, Andreja Rehberger; Šebeštjen, Miran

doi:10.1097/mca.0000000000000272

Cited by 18 publications

(17 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Moreover, in a study by Tritto et al (), TMZ‐induced protection of contractile function in isolated rat heart during ischaemia/reperfusion was linked to inhibition of neutrophil activation, while Chen et al () detected inhibition of the macrophage‐mediated pro‐inflammatory response in mice treated with TMZ prior to endotoxin‐induced cardiomyopathy. Therefore, TMZ might also act via some extramitochondrial, or even extracardiac mechanisms, as suggested by recent studies reporting the effect of TMZ on endothelial function (Rehberger‐Likozar and Sebestjen, ) and whole body insulin sensitivity (Tuunanen et al , ). Some of these effects may, independently of metabolic modulation, confer the clinical improvements associated with TMZ therapy.…”

Section: Discussionmentioning

confidence: 94%

Trimetazidine does not alter metabolic substrate oxidation in cardiac mitochondria of target patient population

Ćavar

Ljubković

Bulat

et al. 2016

British J Pharmacology

View full text Add to dashboard Cite

BACKGROUND AND PURPOSETrimetazidine, known as a metabolic modulator, is an anti-anginal drug used for treatment of stable coronary artery disease (CAD). It is proposed to act via modulation of cardiac metabolism, shifting the mitochondrial substrate utilization towards carbohydrates, thus increasing the efficiency of ATP production. This mechanism was recently challenged; however, these studies used indirect approaches and animal models, which made their conclusions questionable. The goal of the current study was to assess the effect of trimetazidine on mitochondrial substrate oxidation directly in left ventricular myocardium from CAD patients. EXPERIMENTAL APPROACHMitochondrial fatty acid (palmitoylcarnitine) and carbohydrate (pyruvate) oxidation were measured in permeabilized left ventricular fibres obtained during coronary artery bypass grafting surgery from CAD patients, which either had trimetazidine included in their therapy (TMZ group) or not (Control). KEY RESULTSThere was no difference between the two groups in the oxidation of either palmitoylcarnitine or pyruvate, and in the ratio of carbohydrate to fatty acid oxidation. Activity and expression of pyruvate dehydrogenase, the key regulator of carbohydrate metabolism, were also not different. Lastly, acute in vitro exposure of myocardial tissue to different concentrations of trimetazidine did not affect myocardial oxidation of fatty acid. CONCLUSION AND IMPLICATIONSUsing myocardial tissue from CAD patients, we found that trimetazidine (applied chronically in vivo or acutely in vitro) had no effect on cardiac fatty acid and carbohydrate oxidation, suggesting that the clinical effects of trimetazidine are unlikely to be due to its metabolic effects, but rather to an as yet unidentified intracardiac mechanism. Abbreviations

show abstract

Section: Discussionmentioning

confidence: 94%

Trimetazidine does not alter metabolic substrate oxidation in cardiac mitochondria of target patient population

Ćavar

Ljubković

Bulat

et al. 2016

British J Pharmacology

View full text Add to dashboard Cite

show abstract

“…This may be the reason why there is no difference in pain-free walking distance between the two groups of patients after treatment. Trimetazidine has been reported to be able to improve endothelial function (22), and plasmin also to be able to promote endothelial progenitor cell production, repair vascular damage and improve endothelial function (23). The results of the current study showed that the degree of improvement of the two drugs in endothelial function was similar, but all the results had not been verified.…”

Section: Discussionmentioning

confidence: 99%

Efficacy of trimetazidine and plasmin combined with alprostadil in treatment of lower extremity arteriosclerosis obliterans

et al. 2019

View full text Add to dashboard Cite

Clinical efficacy of trimetazidine and plasmin combined with alprostadil in the treatment of lower extremity arteriosclerosis obliterans was investigated. A retrospective analysis was performed on 132 patients with lower extremity arteriosclerosis obliterans treated in Yantai Yuhuangding Hospital from March 2015 to August 2017. Among them, 68 patients were treated with trimetazidine combined with alprostadil (group A), and 64 patients were treated with plasmin combined with alprostadil (group B). Patients were administered 2 courses of treatment and observed with regard to therapeutic effects, changes in blood flow perfusion indicators (vascular peak velocity and blood flow) of the superficial femoral artery, posterior tibial artery and dorsalis pedis artery, in endothelial function, in left ankle brachial index, in pain-free walking distance and in maximum walking distance. After treatment, the vascular peak velocity of group B patients was lower than that in group A (P<0.05), but the blood flow was higher than that in group A (P<0.05). After treatment, endothelial esterase, high-sensitivity C-reactive protein and circulating endothelial cell count levels after treatment were lower than those before treatment (P<0.05), but nitric oxide level was higher than that before treatment (P<0.05). After treatment, the left ankle brachial index was lower in group A of patients than that in group B (P<0.05). After treatment, the maximum walking distance was significantly higher in group A patients than that in group B (P<0.05). After treatment, the pain-free walking distance and maximum walking distance of the two groups of patients were higher than those before treatment (P<0.05). Both trimetazidine and plasmin combined with alprostadil can effectively treat lower extremity arteriosclerosis obliterans. The former is better than the latter in improving exercise capacity, but the latter is better than the former in improving blood flow perfusion in patients.

show abstract

“…У наших пациентов, согласно данным фотоплетизмографии в динамике, отмечалось сопоставимое улучшение струк-турно-функционального состояния крупных артерий при лечении обеими тройными комбинациями антианги-нальных препаратов. Эти данные согласуются с сообще-нием A. Rehberger-Likozar и M. Šebeštjen [31] о том, что лечение триметазидином или ранолазином в равной мере улучшает вызванную потоком и индуцированную нитроглицерином дилатацию плечевой артерии у паци-ентов с ИБС.…”

Section: ишемическая болезнь сердцаunclassified

Therapy of Stable Angina of Effort by Triple Combinations of Antianginal Drugs in Geriatric Practice

Канорский¹,

Смоленская²

2017

Med. sov.

View full text Add to dashboard Cite

С табильная стенокардия является одним из наи-более распространенных заболеваний, сопро-вождающихся высокой заболеваемостью и смертностью, особенно при недостаточной эффективно-сти назначенного лечения [1]. Предотвращение стенокар-дии / ишемии миокарда позволяет улучшать качество жизни пациентов со стабильной ишемической болезнью сердца (ИБС) и, вероятно, способствует продлению их жизни [2,3]. Бета-адреноблокаторы, блокаторы кальцие-вых каналов и нитраты принято называть традиционными антиангинальными средствами с гемодинамическим механизмом действия, которые остаются основой реко-мендованной медикаментозной терапии стабильной сте-нокардии [4]. Между тем увеличение их дозы сопрово-ждается ухудшением переносимости, что особенно часто наблюдается в гериатрической практике. В подобных случаях, при невозможности проведения чрескожной или хирургической реваскуляризации миокарда, могут ока-заться полезными антиангинальные препараты второй линии [5].У больных ИБС пожилого и старческого возраста при-менение бета-адреноблокаторов в дозах, которые обе-спечивают достижение целевой частоты сердечных сокращений, нередко приводит к появлению атриовен-трикулярной блокады и других побочных эффектов. Добавление ивабрадина к сниженной дозе бета-адрено-блокатора оказывается более безопасным и достаточно эффективным, но не устраняет стенокардию полностью [6]. Дальнейшее повышение результативности антианги-нальной терапии возможно при назначении препаратов, не изменяющих атриовентрикулярную проводимость, артериальное давление, автоматизм синусового узла (триметазидин, ранолазин). Однако крупных рандомизи-рованных клинических исследований такого лечения не проводилось.Цель исследования -сравнение эффективности и безопасности антиангинальной терапии у гериатриче-ских пациентов с ИБС сочетаниями бисопролола, ивабра-дина и триметазидина или ранолазина. THERAPY OF STABLE ANGINA OF EFFORT BY TRIPLE COMBINATIONS OF ANTIANGINAL DRUGS IN GERIATRIC PRACTICEThe prospective randomized study of the efficacy and safety of antianginal therapy with a combination of bisoprolol, ivabradine and trimetazidine or ranolazine included 107 patients aged 60 to 79 years with coronary heart disease and angina of effort of functional class II-IIIs. If the angina and/or myocardial ischemia sine dolore in patients receiving bisoprolol and ivabradine after randomization was additionally administered Trimetazidine (35 mg 2 p/day, n = 54) or ranolazine (500 mg 2 p/day, n = 53). Within 6 months both the treatment was well tolerated, significantly improved the results of treadmill exercise test, systolic and diastolic functions of the left ventricle, the structural and functional state of large arteries, quality of life of patients. Trimetazidine largely reduced the duration of painless depression of the ST segment according to Holter electrocardiogram. Combination of low-dose beta-blocker with ivabradine and trimetazidine or ranolazine can be used for the treatment of refractory stable angina in patients of elderly and senile age.

show abstract

Influence of trimetazidine and ranolazine on endothelial function in patients with ischemic heart disease

Abstract: Both trimetazidine and ranolazine led to an improvement in FMD and GTN of the brachial artery in patients with ischemic heart disease, with no statistically significant difference between the groups.

Cited by 18 publications

References 34 publications

Trimetazidine does not alter metabolic substrate oxidation in cardiac mitochondria of target patient population

Trimetazidine does not alter metabolic substrate oxidation in cardiac mitochondria of target patient population

Efficacy of trimetazidine and plasmin combined with alprostadil in treatment of lower extremity arteriosclerosis obliterans

Therapy of Stable Angina of Effort by Triple Combinations of Antianginal Drugs in Geriatric Practice

Contact Info

Product

Resources

About