曲美他嗪在缺血性心脏病中的应用

中国临床药理学与治疗学 ›› 2006, Vol. 11 ›› Issue (4): 385-391.

曲美他嗪在缺血性心脏病中的应用

Acharya Dhan Kumar, 党瑜华

郑州大学第一附属医院心内科, 郑州450052, 河南

收稿日期:2006-02-13 接受日期:2006-03-06 出版日期:2006-04-26 发布日期:2020-12-08

Use of trimetazidine in ischemic heart disease

Acharya Dhan Kumar, DANG Yu-hua

Department of Cardiology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China

Received:2006-02-13 Accepted:2006-03-06 Online:2006-04-26 Published:2020-12-08
Contact: DANG Yu-hua, female, professor, master tutor, engaged in prevention and cure of coronary artery disease. Tel:0371-65169571 　E-mail:dangyuhua@zzu.edu.cn
About author:Acharya DK,male, postgraduate, engaged in prevention and cure of coronary artery disease. Tel:0371-69015501 　E-mail:drdk@hotmail.com

摘要/Abstract

摘要： 缺血性心脏病(IHD) 其病理特点是冠状动脉内粥样斑块, 管腔狭窄或阻塞, 导致心肌缺血, 患者出现胸痛。斑块破裂提供了血小板聚集和血栓形成的场所, 导致不稳定性心绞痛或心肌梗死。稳定性心绞痛常规应用β 阻滞剂、硝酸酯类和钙阻滞剂, 这些药物是通过增加心肌供氧或减少心肌需氧发挥作用的。近年来, 作为代谢调节剂的一组药物, 已充分显示其优势。曲美他嗪是该类药物的代表药, 已发现在缺血心肌中, 脂肪酸氧化增强, 葡萄糖氧化受抑制, 曲美他嗪通过抑制缺血心肌中脂肪酸的氧化, 直接发挥心肌细胞的保护作用。其他的一些研究尚在进行中, 以进一步阐明在与IHD 有直接或间接关系的其他疾病中曲美他嗪的作用。本综述目的是总结近年来世界范围内所做的各种临床试验研究的结果, 以评价该药在IHD 中的作用及其确切机制, 进一步认识其在心肌保护中的真正价值。

关键词: 曲美他嗪, 代谢调节剂, 缺血性心脏病

Abstract: Ischemic heart disease (IHD) is characterized pathologically by the atheromatous plaque which may induce stenosis or obstruction of the coronary arterial lumen leading to myocardial ischemia, experienced by the patients as chest pain.Plaque rupture provides a focus for platelet deposition and thrombosis, and results in unstable angina or myocardial infarction.Stable angina pectoris is treated conventionally by using beta blockers, nitrates and calcium channel blockers (CCB), all of which act by either increasing the supply or decreasing the demand of oxygen in myocardium.In recent years a group of drugs known as metabolic modulators have been particularly shown to be beneficial in protecting the myocardium.Trimetazidine has been a special target in this group.It has been found that in ischemic myocardium there is high rate of fatty acid (FA) oxidation and subsequent inhibition of glucose oxidation.This drug is thought to have direct cytoprotective action in ischemic myocardium through inhibition of the oxidation of FA.Numerous studies are still being carried out to further clarify its roles in various other conditions related directly or indirectly with IHD.The purpose of the review was to assimilate the results of various trials done all over the world in the recent years to find out the role in IHD and the exact mechanism of action, in order to know its true worth in myocardial protection.

Key words: trimetazidine, metabolic modulator, ischemic heart disease

中图分类号:

R541.4

Acharya Dhan Kumar, 党瑜华. 曲美他嗪在缺血性心脏病中的应用[J]. 中国临床药理学与治疗学, 2006, 11(4): 385-391.

Acharya Dhan Kumar, DANG Yu-hua. Use of trimetazidine in ischemic heart disease[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2006, 11(4): 385-391.

参考文献

1 Kantor PF, Lucien A, Kozak R, Lopaschuk GD.The antianginal drug trimetazidine shifts cardiac energy metabolism from FA oxidation to glucose oxidation by inhibiting mitochondrial longchain 3-ketoacyl coenzyme A thiolase[J].Circ Res, 2000;86: 580-8
2 Lopaschuk GD, Barr R, Thomas PD, Dyck JRB.Beneficial effects of trimetazidine in ex vivo working ischemic hearts are due to a stimulation of glucose oxidation secondary to inhibition of long chain 3-ketoacyl coenzyme A thiolase[J].Circ Res, 2003;93:E33
3 Trimetazidine:A well tolerated and novel alternative in stable angina pectoris[J].Drug Ther Perspect, 2000;16:1-5
4 Parker JO.Chronic angina pectoris:Inadequecies of current therapy[J].Am J Geriatr Cardiol, 2004;13:261-6
5 MarzilliM, KleinWW.Efficacy and tolerability of trimetazidine in stable angina:a meta-analysis of randomized, double blind, controlled trials [J].Coron Artery Dis, 2003;14:171-9
6 Lee L, Horowitz J, Frenneaux M.Metabolic manipulation in ischemic heart disease, a novel approach to treatment[J].Eur Heart J, 2004;25:634-41
7 Lopaschuk GD.Inhibiting FA oxidation as a novel therapeutic approach to treating ischemic heart disease[J].Cardiovasc J S Afr, 2004;15:S1
8 Shlyakhto EV, Almazov VV, Nifontov EM, Vakhrameyeva IV, Rudomanov OG, Zakharov DV, et al.Antianginal effects of trimetazidine and left ventricular function improvement in patients with stable angina pectoris[J].Am J Cardio Drugs, 2002;2: 119-24
9 Makolkin VI, Osadchly KK.Trimetazidine modified release in the treatment of stable angina[J].Clin Drug Invest, 2004;24: 731-8
10 Parker JO.Angina pectoris:a review of current and emerging therapies[J].Am J Manag Care, 2004;10:S332-8
11 Pauly DF, Pepine CJ.Ischemic heart disease:Metabolic Approaches to Management[J].Clin Cardiol, 2004;27:439-41
12 Ruzyllo W, Szwed H, Sadowski Z, Elikowski W, Grzelak-Szafranska H, Orszulak W, et al.Efficacy of trimetazidine in patients with recurrent angina:a subgroup analysis of the TRIMPOL II study[J].Curr Med Res Opin, 2004;20:1447-54
13 Detry JM, Leclercq PJ.Trimetazidine European multicenter study versus propranolol in angina pectoris: contribution of Holter electrocardiographic ambulatory monitoring [J].Am J Cardiol, 1995;76:8B-11B
14 Szwed H, Sadowski Z, Elikowski W, Koronkiewicz A, Mamkarz A, Orszulak W, et al.Combination treatment in stable effort angina using trimetazidine and metoprolol.Results of a randomized, double-blind, multicentre study(TRIMPOL II) [J]. Eur Heart J, 2001;22:2267-74
15 Manchanda SC, Krishnaswami S.Combination treatment with trimetazidine and diltiazem in stable angina pectoris[J].Heart, 1997;78:353-7
16 Manchanda SC.Treatment of stable angina with low dose diltiazem in combination with the metabolic agent trimetazidine[J]. Int J Card Imaging, 2003;88:83-9
17 Koylan N, Bilge AK, Adalet K, Mercanoglu F, Buyukozturk K, TTS group.Comparision of the effects of trimetazidine and diltiazem on exercise performance in patients with coronary heart disease.The Turkish trimetazidine study (TTS) [J].Acta Cardiol, 2004;59:644-50
18 Chazov EI, Lepakchin VK, Zharova EA, Fitilev SB, Levin AM, Rumiantzeva EG, et al.Trimetazidine in angina combination therapy-the TACT study:trimetazidine versus conventional treatment in patients with stable angina pectoris in a randomized, placebo controlled, multicenter study [J].Am J Ther, 2005;12:35-42
19 Karpov RS, Koshel, Skaia OA, Chernov VI, Ocheredko NA, Efimova EV, et al.Clinical efficacy of combination therapy with trimetazidine and angiotensin converting enzyme inhibitors in patients with hypertension and ischemic heart disease associated with type II diabetes[J].Kardiologiia, 2004;44:43-7
20 Szwed H.Clinical benefits of trimetazidine in patients with recurrent angina[J].Coron Artery Dis, 2004;15:S17-21
21 The emip-fr group.Effect of 48-h intravenous trimetazidine on short-and long-term outcomes of patients with acute myocardial infarction, with and without thrombolytic therapy.A doubleblind, placebo-controlled, randomized trial[J].Eur Heart J, 2000;21:1537-46
22 Rogacka D, Guzik P, Wykretowicz A, Rzezniczak J, Dziarmaga M, Wysocki H, et al.Effects of trimetazidine on clinical symptoms and tolerance of exercise of patients with syndrome X: a preliminary study[J].Coron Artery Dis, 2000;11:171-7
23 Vitale C, WajngatenM, Sposato B, Gebara O, Rossini P, Fini M, et al.Trimetazidine improves left ventricular function and quality of life in elderly patients with coronary artery disease [J].Eur Heart J, 2004;25:1814-21
24 Essop MF, Opie LH.Metabolic therapy for heart failure[J]. Eur Heart J, 2004;25:1765-8
25 Fragasso G, Piatti PM, Monti L, Palloshi A, Setola E, Pucetti P, et al.Short-and long-term beneficial effects of trimetazidine in patients with diabetes and ischemic cardiomyopathy[J].Am Heart J, 2003;146:E18
26 Rosano GMC, Vitale C, Sposato B, Mercuro G, FiniM.Trimetazidine improves left ventricular function in diabetic patients with coronary artery disease:a double-blind placebo-controlled study[J].Cardiovasc Diabetol, 2003;2:16
27 Korantzopoulos P, Kountouris E, Siogas K, Galaris D.The potential benefits of trimetazidine in patients with diabetes and ischemic cardiomyopathy[J].Am Heart J, 2004;148:E31
28 Morillas P, Hernandez A, Pallares V, Bertomeu V, Roldan FJ, Capdevilla C, et al.Usefulness of trimetazidine in ischemia-reperfusion lesion.Experimental study in myocardial stunning model[J].Arch Cardiol Mex, 2004;74:262-70
29 Baumert H, Faure JP, Zhang K, Petit I, Goujon JM, Dutheil D, et al.Evidence for a mitochondrial impact of trimetazidine during cold ischemia and reperfusion[J].Pharmacology, 2004; 71:25-37
30 Barsotti A, Di Napoli P.Trimetazidine and cardioprotection during ischemia-reperfusion[J].Ital Heart J, 2004;5:29S-36S

[1]	盛洋，张田杰. 曲美他嗪对稳定型心绞痛患者血清同型半胱氨酸及谷氨酰转肽酶含量的影响[J]. 中国临床药理学与治疗学, 2018, 23(8): 922-926.
[2]	杨柳, 郭毅. 曲美他嗪联合麝香保心丸治疗慢性心力衰竭疗效的Meta分析[J]. 中国临床药理学与治疗学, 2014, 19(6): 644-650.
[3]	朱刚艳, 徐红新, 田毅浩, 马红梅, 唐世琪, 汪福良, 邬松林. 曲美他嗪通过上调Bcl-2改善骨髓间质干细胞存活[J]. 中国临床药理学与治疗学, 2011, 16(7): 729-735.
[4]	张品, 何胜虎, 陈述, 张惹, 严风姊, 燕建峰, 赵福全, 徐返华. 曲美他嗦对非ST段抬高急性冠脉综合征患者心肌缺血和心率变异的影响[J]. 中国临床药理学与治疗学, 2007, 12(12): 1432-1435.
[5]	谢明星, 王新房, 朱向明, 杨娅, 吕清, 陈立新, 聂绍平, 蒋桔泉, 曹林生. 急性心肌缺血激光心肌血管重建术与碱性成纤维生长因子联合应用对心脏功能及心肌存活性影响的实验研究¹[J]. 中国临床药理学与治疗学, 2003, 8(2): 149-154.
[6]	单守杰, 陈绍良. 骨髓干细胞移植治疗缺血性心脏病的研究进展[J]. 中国临床药理学与治疗学, 2002, 7(5): 473-476.