负荷量曲美他嗪对冠心病合并高脂血症患者内皮功能的影响
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摘要
目的:冠心病是危害人类健康和生命的重要疾病之一,在人类死因构成比中占首位。而内皮功能不全可以导致冠状动脉血管张力调节机能受损并且启动粥样硬化的过程。近年来的研究发现,血管内皮不是简单的血液容器,而是一个具有内分泌及代谢功能的器官,具有选择性屏障作用。一旦内皮受损伤,可导致血小板聚集进而形成血栓,是冠状动脉粥样硬化过程的早期表现。在引起内皮功能不全的诸多因素中,高脂血症导致的血管内皮功能受损是动脉粥样化的始发因素。高脂血症患者在动脉粥样硬化斑块形成之前已经存在血管内皮功能失调,内皮依赖性血管舒张功能障碍是其主要表现,被抑制的血管舒张反应不仅包括大动脉,还包括循环阻力血管。血脂异常与内皮功能的损害关系密切,即使没有AS的存在,也表现为内皮功能障碍。冠心病、内皮功能障碍、高脂血症之间有着密切的关系。因此选用一种既抗心肌缺血又能改善内皮细胞功能的药物成为治疗冠心病的一种有效途径。曲美他嗪(TMZ)是第一个3-酮酰基辅酶A硫解酶抑制剂,除了具有改善缺血心肌细胞的作用,还能间接激活一氧化氮合成酶,介导血管舒张因子的生成,即改善内皮功能。其改善心肌细胞缺血的作用已得到证实并广泛应用于临床,但其改善内皮功能的作用,尚未得到充分的研究,报道甚少。
本研究旨在观察负荷量曲美他嗪(60mg),两小时后,一氧化氮(NO)水平、肱动脉内皮依赖性血管舒张功能(FMD)的变化,探讨负荷量曲美他嗪对冠心病合并高脂血症患者内皮细胞功能的影响。
方法:入选60例冠心病合并高脂血症的患者,并且除外高血压及糖尿病,男47例,女13例,年龄30-75岁,平均年龄51.32±8.36岁。入选患者经冠状动脉造影证实为冠心病(依据国际通用的直径法评定冠状动脉狭窄程度,凡狭窄≥50%者定为CHD,<50%者为NCHD),并检测患者入院后第2天清晨空腹血脂,血糖水平(除外糖尿病),并确定该患者患有高脂血症(总胆固醇超过5.72mmol/L)。入院后第3日在患者病情稳定的情况下检测NO水平,并即刻作肱动脉超声检测基础状态下肱动脉内径的基础值D0,然后予肱动脉加压,检测肱动脉反应性充血内径D1,并计算出肱动脉内皮依赖性血管舒张功能(FMD),随后立刻给予负荷量盐酸曲美他嗪(万爽力,法国施维雅药厂)60mg,两小时后检测NO水平,并再次作肱动脉超声,检测FMD。
结果:
1.顿服负荷量曲美他嗪60mg两小时后,血浆NO水平较服药前明显升高(46.01±6.74 vs 43.86±7.08 umol/L, P<0.05)。
2.肱动脉内皮依赖性血管舒张功能FMD(%)较服药前明显增加(10.65±2.83 vs 9.89±2.27 %, P<0.05).
结论:
1.患者顿服负荷量曲美他嗪60mg,两小时后NO水平较用药前明显升高,说明负荷量曲美他嗪对内皮功能有改善作用。
2.患者服药两小时后肱动脉内皮依赖性血管舒张功能(FMD)较用药前明显升高,说明负荷量曲美他嗪能够改善内皮功能。
3.患者顿服盐酸曲美他嗪片(万爽力)60mg后未见不良反应。
Objective: Coronary heart disease is one of the major diseases in humans harmful to human health and life . Constitute of a cause of death accounted for more than the first. Endothelial dysfunction can lead to coronary vascular tone control mechanism may be damaged and start the process of atherosclerosis. In recent years, studies have found that vascular endothelium is not a simple blood vessel, but is the organ of endocrine , metabolic and selective barrier function. Once the injured endothelium is injured, it may lead to platelet aggregation and the formation of thrombosis, it is the early performance in coronary atherosclerosis process. Many factors can cause endothelial dysfunction .The Hyperlipidemia caused by impaired vascular endothelial function is the starting atherogenic factors. Hyperlipidemia patients had already existed atherosclerotic plaques in the arteries before vascular endothelium dysfunction, endothelium-dependent vasodilatation dysfunction is the main performance, suppressed vasodilator responses include not only the aorta, but also resistance vascular. Dyslipidemia closely related to endothelial function dysfunction, even without the presence of AS, but also showed endothelial dysfunction. There is a close relationship between Coronary heart disease, endothelial dysfunction, and hyperlipidemia. Select one not only can improve endothelial cell function but also anti-ischemic drugs that as an effective way of treating coronary heart disease. Trimetazidine (trimetazidine TMZ) - long-chain 3 - keto acyl coenzyme A thiolase (3-KAT) inhibitors, besides improve myocardial cell metabolism and can also activate nitric oxide synthase indirectly therefore mediate vascular relaxing factor generation which means improvement of endothelial function.Its role in improving myocardial ischemia has been confirmed and widely used in clinical, but its role in improving endothelial function, has not been adequate research, the report very few. This study was designed by observing the load trimetazidine (Vasorel, Wan Shuang Li, made by the French pharmaceutical firm Servier) 60mg after two hour, the level of nitric oxide (NO) and the change of endothelium-dependent vasodilatation (FMD)of brachial artery to study the effects of load trimetazidine on endothelial function of coronary heart disease combined hyperlipidemia .
Methods: 60 excepted for a history of hypertension and diabetes patients with coronary heart disease combined hyperlipidemia were enrolled in this study (47 male, 13 female, aged 30-75, average 51.32±8.36). Selected patients with coronary heart disease confirmed by coronary angiography (The diameter of law based on internationally accepted assessment of coronary artery stenosis, the diameter≥50% stenosis were defined as CHD, and the diameter<50% stenosis were defined as NCHD). The fasting blood lipids and fasting blood glucose (except for diabetes mellitus) were detected on the second day after admission to determine the patient suffering from hyperlipidemia(Total cholesterol of more than 5.72mmol / L). NO were detected on the third day after admission in the case of patients in stable condition, and immediately to the brachial artery ultrasound baseline brachial artery diameter, under the basis of the value of D0, and then to the brachial artery pressure, detection of reactive hyperemia brachial artery diameter D1, and calculate endothelium-dependent vasodilatation(FMD) of brachial artery , then immediately given load trimetazidine 60mg, after two hours detected NO levels, and once again made the brachial artery ultrasound to detected FMD.
Results:
1. Load trimetazidine 60mg after 2 hours,the plasma NO level was significantly higher than before treatment (46.01±6.74 vs 43.86±7.08umol/L, P<0.05).
2. FMD% increased than before treatment (10.65±2.83 vs 9.89±2.27%, P<0.05).
Conclusion:
1. Loading dose of trimetazidine 60mg after two hours, the NO level was significantly higher than that before treatment, indicating loading dose of trimetazidine has improvement on endothelial function .
2. Brachial artery endothelium-dependent vasodilation (FMD) was significantly higher than that before treatment, clarifying the load of trimetazidine has improved on endothelial function.
3. No adverse reaction related to trimetazidine was found.
本研究旨在观察负荷量曲美他嗪(60mg),两小时后,一氧化氮(NO)水平、肱动脉内皮依赖性血管舒张功能(FMD)的变化,探讨负荷量曲美他嗪对冠心病合并高脂血症患者内皮细胞功能的影响。
方法:入选60例冠心病合并高脂血症的患者,并且除外高血压及糖尿病,男47例,女13例,年龄30-75岁,平均年龄51.32±8.36岁。入选患者经冠状动脉造影证实为冠心病(依据国际通用的直径法评定冠状动脉狭窄程度,凡狭窄≥50%者定为CHD,<50%者为NCHD),并检测患者入院后第2天清晨空腹血脂,血糖水平(除外糖尿病),并确定该患者患有高脂血症(总胆固醇超过5.72mmol/L)。入院后第3日在患者病情稳定的情况下检测NO水平,并即刻作肱动脉超声检测基础状态下肱动脉内径的基础值D0,然后予肱动脉加压,检测肱动脉反应性充血内径D1,并计算出肱动脉内皮依赖性血管舒张功能(FMD),随后立刻给予负荷量盐酸曲美他嗪(万爽力,法国施维雅药厂)60mg,两小时后检测NO水平,并再次作肱动脉超声,检测FMD。
结果:
1.顿服负荷量曲美他嗪60mg两小时后,血浆NO水平较服药前明显升高(46.01±6.74 vs 43.86±7.08 umol/L, P<0.05)。
2.肱动脉内皮依赖性血管舒张功能FMD(%)较服药前明显增加(10.65±2.83 vs 9.89±2.27 %, P<0.05).
结论:
1.患者顿服负荷量曲美他嗪60mg,两小时后NO水平较用药前明显升高,说明负荷量曲美他嗪对内皮功能有改善作用。
2.患者服药两小时后肱动脉内皮依赖性血管舒张功能(FMD)较用药前明显升高,说明负荷量曲美他嗪能够改善内皮功能。
3.患者顿服盐酸曲美他嗪片(万爽力)60mg后未见不良反应。
Objective: Coronary heart disease is one of the major diseases in humans harmful to human health and life . Constitute of a cause of death accounted for more than the first. Endothelial dysfunction can lead to coronary vascular tone control mechanism may be damaged and start the process of atherosclerosis. In recent years, studies have found that vascular endothelium is not a simple blood vessel, but is the organ of endocrine , metabolic and selective barrier function. Once the injured endothelium is injured, it may lead to platelet aggregation and the formation of thrombosis, it is the early performance in coronary atherosclerosis process. Many factors can cause endothelial dysfunction .The Hyperlipidemia caused by impaired vascular endothelial function is the starting atherogenic factors. Hyperlipidemia patients had already existed atherosclerotic plaques in the arteries before vascular endothelium dysfunction, endothelium-dependent vasodilatation dysfunction is the main performance, suppressed vasodilator responses include not only the aorta, but also resistance vascular. Dyslipidemia closely related to endothelial function dysfunction, even without the presence of AS, but also showed endothelial dysfunction. There is a close relationship between Coronary heart disease, endothelial dysfunction, and hyperlipidemia. Select one not only can improve endothelial cell function but also anti-ischemic drugs that as an effective way of treating coronary heart disease. Trimetazidine (trimetazidine TMZ) - long-chain 3 - keto acyl coenzyme A thiolase (3-KAT) inhibitors, besides improve myocardial cell metabolism and can also activate nitric oxide synthase indirectly therefore mediate vascular relaxing factor generation which means improvement of endothelial function.Its role in improving myocardial ischemia has been confirmed and widely used in clinical, but its role in improving endothelial function, has not been adequate research, the report very few. This study was designed by observing the load trimetazidine (Vasorel, Wan Shuang Li, made by the French pharmaceutical firm Servier) 60mg after two hour, the level of nitric oxide (NO) and the change of endothelium-dependent vasodilatation (FMD)of brachial artery to study the effects of load trimetazidine on endothelial function of coronary heart disease combined hyperlipidemia .
Methods: 60 excepted for a history of hypertension and diabetes patients with coronary heart disease combined hyperlipidemia were enrolled in this study (47 male, 13 female, aged 30-75, average 51.32±8.36). Selected patients with coronary heart disease confirmed by coronary angiography (The diameter of law based on internationally accepted assessment of coronary artery stenosis, the diameter≥50% stenosis were defined as CHD, and the diameter<50% stenosis were defined as NCHD). The fasting blood lipids and fasting blood glucose (except for diabetes mellitus) were detected on the second day after admission to determine the patient suffering from hyperlipidemia(Total cholesterol of more than 5.72mmol / L). NO were detected on the third day after admission in the case of patients in stable condition, and immediately to the brachial artery ultrasound baseline brachial artery diameter, under the basis of the value of D0, and then to the brachial artery pressure, detection of reactive hyperemia brachial artery diameter D1, and calculate endothelium-dependent vasodilatation(FMD) of brachial artery , then immediately given load trimetazidine 60mg, after two hours detected NO levels, and once again made the brachial artery ultrasound to detected FMD.
Results:
1. Load trimetazidine 60mg after 2 hours,the plasma NO level was significantly higher than before treatment (46.01±6.74 vs 43.86±7.08umol/L, P<0.05).
2. FMD% increased than before treatment (10.65±2.83 vs 9.89±2.27%, P<0.05).
Conclusion:
1. Loading dose of trimetazidine 60mg after two hours, the NO level was significantly higher than that before treatment, indicating loading dose of trimetazidine has improvement on endothelial function .
2. Brachial artery endothelium-dependent vasodilation (FMD) was significantly higher than that before treatment, clarifying the load of trimetazidine has improved on endothelial function.
3. No adverse reaction related to trimetazidine was found.
引文
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23 Ihling C, Bohrmann B, Schaefer HE, et al.Endothelin-1 and endothelinconverting enzyme-1 in human atherosclerosis-novel targets for pharmacotherapy in atherosclerosis. Curr Vasc Pharmacol, 2004, 2(3): 249-258
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2 Seiler C,Hess OM,Buechi M,et al. Influence of serum cholesterol and other coronary risk factors vasomotion of angiographically nomal coronary arteries. Circulation ,1993,88(5 Pt 1) :2139-2148
3 Uehata A,Gerhard MD,Meredith IT,et al. Close relation of endothelial function in the human coronary and peripheral circulations.J Am Coll Cardiol,1995,26(5):1235-1241
4 Di Napoli P,Chierchia S,Taccardi AA.et al.Trimetazidine improves post-ischemic recovery by preserving endothelial nitric oxide synthase expression in isolated working rat hearts. Nitric Oxide,2007 ,16(2):228-36
5 Monti LD,Allibardi S, Piatti PM, et al. Triglycerides impair postischemicrecovery in isolate hearts: roles of endothelin-1and trimetazidine. Am J Physiol Heart CircPhysiol, 2001, 281 (3): H1122-H1130
6许玉韵,胡大一.心电图与冠状动脉造影.北京:人民卫生出版社,2006:34-35
7 Celermajer DS, Sorensen KE,Gooch VM, et al.Non-invasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis.Lancet ,1992, 340(8828):1111-1115
8 Abrams J. Role of endothelial dysfunction in coronary artery disease.Am J Cardiol,1997, 79(12B):2-9
9 Chen-H, Ikeda-U, Shimpo-M, et al. Direct effects of statins on cells primarily involved in atherosclerosis. Hypertens Res, 2000,23(2): 187-192
10 Jin ZG, Ueba H, Tanimoto T, et al. Ligand-independent activation of vascular endothelial growth factor receptor 2 by fluid shear stress regulates activation of endothelial nitric oxide synthase. Circ Res, 2003,93(4):354-363
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