5-单硝酸异山梨酯对稳定型心绞痛长期抗心肌缺血作用的观察

5-单硝酸异山梨酯是一种硝酸酯类抗心绞痛药物，是硝酸异山梨酯的主要代谢产物，单硝酸酯的抗心绞痛作用与其母药物类似，并认为硝酸酯类主要血管活性是这些代谢产物的作用结果。5-单硝酸异山梨酯具有吸收完全，无明显首过效应，生物利用度高，作用持续时间长等特点，已广泛应用于心绞痛的预防和治疗瞳]。用动态心电图检测心肌缺血总负荷（TIB）及核素心肌显像估测心肌缺血面积（IMA），结合临床缺血相关事件为指标，报告口服单硝酸异山梨酯20mg（商品名：山苏）6个月对稳定型心绞痛患者的长期抗心肌缺血作用。     

西拉普利对心肌梗塞患者的长期抗缺血作用

目的探讨血管紧张素转换酶抑制剂（ACEI）减少心肌梗塞后患者心肌缺血及其相关事件的作用。方法87例心肌梗塞后患者随机分为45例服用西拉普利（治疗组）和42例常规治疗（对照组），于出院前，出院后3个月、6个月和1年行24h动态心动图心肌缺血总负荷检测（TIB）并观察缺血相关事件。结果治疗组TIB在出院后6个月低于对照组，但无统计学差异（P＞0.05）。出院后1年，治疗组TIB显著低于对照组（P＜0.05），在出院后12个月中，治疗组的缺血相关事件明显少于对照组（P＜0.05），但出院后头6个月两组差异并不明显，直至出院后6个月才呈现出明显的差异。结论西拉普利对心肌梗塞后患者具有长期的抗心肌缺血和减少缺血相关事件的作用。     

ACEI对AMI后患者长期抗缺血及降低缺血事件的作用

目的：观察血管紧张素转换酶抑制剂（ACEI）减少急性心肌梗塞（AMI）后患心肌缺血及其相关事件的影响。方法：将87例AMI后患随机分为43例服用开搏通治疗组和44例常规治疗对照组，于出院前、出院后3个月、6个月和1年行hoter心肌缺血总负荷检测（TIB），并观察缺血相关事件。结果：于出院后1年，治疗组TIB才显低于对照组（P＜0．05），并且缺血相关事件明显少对照组（P＜0．05），但出院后前6个月丙组差异并不明显，至出院后6个月才出现明显的差异，结论：ACEI对AMI后患具有长期的抗缺血和减少缺血事件的使用。     

单硝酸异山梨酯的制备

单硝酸异山梨酯（IsosorbideMononitrate，商品名：异乐定）是抗心肌缺血药硝酸异山梨酯体内主要活性代谢产物[1]，是无首过代谢的长效硝酸盐，口服吸收迅速，生物利用度高，达到100％；有效血药浓度稳定，持续时间长，其半衰期间／2约在5h左右；个体差异小，无药物交互作用，可适用于冠心病的长期治疗，预防心肌梗塞后持续的症状，特别适用于冠心病心绞痛的防治。本文只就实验室合成单硝酸异山梨酯的方法进行探索，选择最佳的合成途径。1·异山梨醇（IS）直接硝化法：[2]合成路线为：这种方法的缺点是反应生成物是四种化合物的混合物，包…     

静脉滴注单硝酸异山梨酯治疗冠心病心绞痛的临床疗效观察

目的：探讨静脉滴注单硝酸异山梨酯治疗冠心病心绞痛的有效性。方法选取48例冠心病心绞痛患者,随机均分为对照组（硝酸甘油静脉滴注）和观察组（单硝酸异山梨酯静脉滴注）,对两组患者经治疗后的心绞痛症状及心电图改善情况进行综合比较。结果观察组心绞痛症状改善有效率为91.7%,显著高于对照组的66.7%（P＜0.05）;观察组心电图改善有效率为87.5%,显著高于对照组的62.5%（P＜0.05）。结论静脉滴注单硝酸异山梨酯治疗冠心病心绞痛疗效确切,可减少心绞痛发作,改善患者心肌缺血症状。     

让合理、安全用药知识(五十二) 走进千家万户

正(接上期)四、抗心绞痛药2.单硝酸异山梨酯(5-单硝酸异山梨醇、5-单硝酸异山梨醇酯、5-单硝酸异山梨酯、长效心痛治、异乐定)新一代长效硝酸酯类抗心绞痛药,作用机制与硝酸甘油相同,但作用时间较长。临床用于:1.用于冠心病的长期治疗;预防劳累性心绞痛、变异型心绞痛及混合     

让合理、安全用药知识(五十二) 走进千家万户

(接上期)四、抗心绞痛药2.单硝酸异山梨酯(5-单硝酸异山梨醇、5-单硝酸异山梨醇酯、5-单硝酸异山梨酯、长效心痛治、异乐定)新一代长效硝酸酯类抗心绞痛药,作用机制与硝酸甘油相同,但作用时间较长。临床用于:1.用于冠心病的长期治疗;预防劳累性心绞痛、变异型心绞痛及混合     

心肌灌注断层显像评价丹红注射液对不稳定型绞痛患者缺血心肌活性状态的影响

目的采用99m锝-甲氧基异丁基异腈（99mTc-MIBI）心肌单光子发射计算机断层（SPECT）灌注显像,定量评价缺血心肌面积（IMA）变化,以便更客观地评价丹红注射液对不稳定心绞痛患者缺血心肌活性状态的影响。方法将66例患者随机分为对照组和丹红组。对照组33例,单独用常规治疗;丹红组33例,在对照组治疗的基础上加用丹红注射液30ml加5％葡萄糖注射液或生理盐水250ml静脉滴注。于治疗后14d对两组进行SPECT检测。对两组心肌缺血面积的变化进行对比研究。结果治疗两周后比较IMA丹红组明显小于对照组,两组间对比有显著性差异,（P〈0．05）。结论丹红注射液可减少心肌缺血面积,对有效改善缺血心肌的血供和活性状态有显著疗效。     

5—单硝酸异山梨酯治疗冠心病心绞痛45例

目的;观察５－硝酸异山梨酯治疗４５例冠心病心绞痛的疗效。方法：冠心病心绞痛４５例,给予５－单硝酸异山梨酯片剂口服,剂量为２０ｍｇ,Ｂｉｄ,疗程４周,观察心电图,心肌耗氧量及不良反应。结果：冠心病心绞痛患者经５－单硝酸异山梨酯治疗后,心电图,心肌耗氧量比治疗前有显著改善（Ｐ〈０．０５）,结论：５－单硝酸异山梨酯治疗冠心病心绞痛简单易行,安全可靠。     

注射用单硝酸异山梨酯治疗慢性心力衰竭的疗效观察

目的：评价注射用单硝酸异山梨酯治疗慢性心力衰竭的效果。方法：选择2007年1月～2009年12月慢性心力衰竭患者72例,将其随机分为两组,对照组36例,采用常规治疗,治疗组36例,在常规治疗的基础上,采用注射用单硝酸异山梨酯20mg加入5%葡萄糖注射液250mg,以40mg/min初始量静点,以后根据心力衰竭控制情况及血压调节情况,调整用量40～80μg/min持续静点3～5d,两组患者均观察1周,治疗前后比较心功能改善情况。结果：注射用单硝酸异山梨酯治疗慢性心力衰竭能有效改善患者的心功能。治疗组治疗后心功能改善总有效率为91.66%,其中,显效21例（58.33%）,有效12例（33.33%）,无效3例（8.34%）。对照组治疗后心功能改善总有效率为75.00%,其中,显效12例（33.33%）,有效15例（41.67%）,无效9例（25%）。治疗组总有效率明显高于对照组（P〈0.05）。结论：单硝酸异山梨酯治疗后能显著减轻心脏负担,达到明显改善心功能的作用,疗效比常规对照组有明显提高。     

曲美他嗪治疗慢性肾衰竭合并冠心病稳定型心绞痛的临床疗效

目的:研究慢性肾衰竭患者合并冠心病稳定型心绞痛使用曲美他嗪治疗的临床疗效.方法:选取慢性肾衰竭合并冠心病稳定型心绞痛患者65例,分为曲美他嗪组与硝酸异山梨酯组,治疗4周.观察心绞痛发作次数、心率、血压、心电图、动态心电图变化.结果:曲美他嗪组与硝酸异山梨酯组治疗后明显减少心绞痛发作次数,临床症状改善,运动耐力增加,ECG运动试验,ST段下降1 mm时间延长,而两组对比差异无显著性.结论:曲美他嗪与硝酸异山梨酯治疗慢性肾衰竭合并冠心病稳定型心绞痛有相似疗效.     

单硝酸异山梨酯缓释片与缓释胶囊治疗冠心病心绞痛的比较

目的 :比较单硝酸异山梨酯的缓释片与缓释胶囊治疗冠心病心绞痛的疗效。方法 :冠心病心绞痛病人 58例 ,随机分为缓释片组 30例 ,给缓释片60mg ,po ,qd ,共 4wk ;缓释胶囊组 2 8例 ,给缓释胶囊 50mg ,po ,qd ,共 4wk。结果 :缓释片组心绞痛有效率及心电图改善率分别为 93%和 57% ;缓释胶囊组依次为 93%和 61% ,组间比较差别无显著意义 (P >0 .0 5)。 2药不良反应均轻微。结论 :2种单硝酸异山梨酯缓释剂型治疗冠心病心绞痛疗效相近     

Withdrawal of intravenous glyceryl trinitrate: absence of rebound phenomena with transition to oral isosorbide dinitrate

1. Glyceryl trinitrate (GTN) is frequently infused intravenously as a component of the management of acute coronary syndromes (ACS). Abrupt cessation of GTN infusion after periods of more than 24 h administration often induces rebound vasoconstriction reflecting 'pseudotolerance'; this is also the basis of the 'zero hour phenomenon' during chronic nitrate therapy. The efficacy of oral nitrate regimens to prevent vasoconstriction following cessation of intravenous GTN has not been previously examined. Therefore, we investigated the effects of transition from intravenous GTN to oral isosorbide dinitrate (ISDN) on a parameter of apparent arterial stiffness in patients with ACS. 2. The effects of GTN infusion at 5 microg/min on augmentation index (AIx) were quantified in patients (n = 10) with stable angina pectoris in order to establish the magnitude of effect on apparent arterial stiffness. 3. This infusion rate of GTN reduced AIx from 23 +/- 10% (SD) to 3 +/- 14% (SD) (P < 0.01). The effect of transition from GTN infusion of greater than 24 h duration to ISDN (10 mg tds) were examined in patients (n = 16) with ACS (unstable angina/non-Q-wave myocardial infarction). No patient developed recurrent angina during the 24 h following cessation of GTN infusion. The level of AIx was 8 +/- 4% (SD) prior to GTN cessation and fell to 5 +/- 6% (SD) on ISDN (P = 0.05). 4. Thus, in patients treated for ACS, transition from intravenous GTN to low dose oral ISDN is associated with an incremental vasodilatation and no evidence of 'rebound' ischaemia.     

Continuous oral N-acetylcysteine treatment and development of nitrate tolerance in patients with stable angina pectoris.

The presence of sulfhydryl (SH) groups appears to be fundamental to nitrate-induced vasodilation and N-acetylcysteine (NAC), a sulfhydryl (SH)-donor substance, potentiates hemodynamic responsiveness to nitrates. We investigated the effect of simultaneous administration of NAC and isosorbide dinitrate (ISDN) on development of nitrate tolerance. In a double-blind, randomized, placebo-controlled cross-over study, seven patients with stable angina pectoris were treated for two 8-day periods with ISDN (40 mg four times daily, q.i.d.) together with NAC (controlled release 600 mg q.i.d.) or matching placebo. Bicycle exercise tests were performed before treatment was started, 1 h after treatment was started, and at day 8. After 8-day treatment with ISDN + placebo, responses determined by exercise testing were diminished as compared with responses obtained during acute therapy and did not differ from baseline values, suggesting development of tolerance to ISDN. During treatment with ISDN + NAC, time to 1-mm ST depression was significantly prolonged (441 +/- 44 vs. 381 +/- 40 s, mean +/- SEM) and total ST segment depression significantly reduced (1.9 +/- 0.7 vs. 3.5 +/- 0.8 mm) as compared with baseline values. The reduction in ST segment depression was significantly more pronounced during ISDN + NAC (46%) as compared with ISDN + placebo (23%). Although exercise time and time to angina pectoris were unaffected. NAC augmented the antiischemic effects of ISDN as assessed by ECG. This finding may suggest that development of nitrate tolerance is modified by chronic oral high-dose NAC administration.     

诺迪康胶囊治疗稳定型心绞痛

目的 :观察诺迪康胶囊对稳定型心绞痛的临床疗效和对血液流变学的影响。方法 :采取随机单盲对照法 ,12 0例稳定型心绞痛病人分为 2组 ,每组 60例。其中诺迪康组给予诺迪康胶囊 2粒 ,po ,tid× 4wk。硝酸异山梨酯组给予硝酸异山梨酯 10mg ,po ,tid× 4wk。结果 :诺迪康组临床总有效率93% ,心电图总有效率 73% ;硝酸异山梨酯组则依次为 90 %和 70 % (P >0 .0 5)。诺迪康胶囊还能降低血压 ,治疗前后血压为 ( 10 .5± 2 .7) /( 2 0 .2±2 .7)kPa和 ( 9.0± 2 .4 ) /( 18± 4 )kPa(P <0 .0 5)并显著地改善病人的血液流变学指标。结论 :诺迪康胶囊治疗冠心病稳定型心绞痛疗效确切     

Role of Metabolically Active Drugs in the Management of Ischemic Heart Disease

This article reviews the fundamentals of myocardial energy metabolism and selectively outlines the use of several metabolically active drug therapies in the treatment of ischemic heart disease. These drugs — ranolazine, trimetazidine, dichloroacetate (DCA), glucose-insulin-potassium (GIK) solutions, and L-carnitine — have mechanisms of action distinct from traditional anti-ischemic drugs. These agents work by shifting myocardial energy metabolism away from fatty acids toward glucose as a source of fuel. Because these agents are well tolerated and do not affect heart rate or blood pressure, they conceivably could supplement traditional anti-ischemic drug therapy with little risk. The background, rationale for use, and published literature on each agent is reviewed, and the outcomes of pertinent clinical trials are discussed. In the case of ranolazine, data suggest benefit in the treatment of stable angina pectoris, particularly with sustained release formulations. Trimetazidine appears to have similar physiologic effects to ranolazine, and it is effective as monotherapy and as additive therapy in patients with chronic ischemic heart disease. DCA improves acidosis in critically ill patients and, likewise, improves myocardial hemodynamics in those with chronic coronary artery disease and congestive heart failure; however, its metabolism is variable and clinical data on its use in chronic ischemic heart disease are limited. GIK solutions have been shown to be beneficial in animal and human models of ischemia and acute myocardial infarction, and they offer an inexpensive means by which to improve the oxidation of glucose in the heart. Lastly, a large body of literature suggests a benefit with L-carnitine in a number of cardiovascular illnesses, including ischemic heart disease. Clinical trial data in acute myocardial infarction are promising and have prompted the initiation of a large-scale mortality trial.     

New drug forms of isosorbide dinitrate: the problem of an objective evaluation in patients with ischemic heart disease

In 7 patients with ischemic heart disease and stable angina pectoris the efficacy of three oral isosorbide dinitrate (ID) formulations, nitrosorbide, isodinite and isodinite-retard, was compared. The antianginal and anti-ischemic effects were assessed in terms of exercise treadmill tests performed prior to and repeatedly after (2, 5 and 7 hours) single-dose administration (in comparison with placebo). The efficacy of isodinite-retard only slightly differed from that of placebo. Isodinite had a more pronounced effect than nitrosorbide, although the duration of isodinite effect was shorter than that of nitrosorbide. Plasma ID and its metabolite, isosorbide-5-mononitrate concentrations mirrored exercise duration changes. ID content in the tablets of all formulations studied corresponded to those indicated by the manufacturer. The differences in the efficacy of ID formulations can be attributed to the differences in their bioavailability. Thus, the method used permitted to reveal significant distinctions in the efficacy of different ID formulations. These distinctions must be taken into account in clinical practice.     

单硝酸异山梨酯静脉滴注治疗冠心病心绞痛的疗效观察

目的:观察单硝酸异山梨酯静脉滴注治疗冠心病心绞痛的临床疗效。方法:将80例心绞痛患者随机分成2组,治疗组40例,给予单硝酸异山梨酯注射液40m g加入5%葡萄糖溶液250mL静脉滴注。对照组40例给予硝酸甘油15m g加入5%葡萄糖溶液250mL静脉滴注。结果:治疗组总有效率92.50%,对照组总有效率75.00%。差异有统计学意义(P<0.05)。结论:单硝酸异山梨酯注射液静脉滴注治疗冠心病心心绞痛用药安全,临床疗效显著。     

硝酸异山梨酯静脉内输注治疗冠心病心绞痛102例

目的：比较国产与进口硝酸异山梨酯注射液治疗冠心病心绞痛的疗效。方法：冠心病心绞痛病人１５２例，其中１０２例（男性６７例，女性３５例，年龄６３±ｓ９ａ）以国产硝酸异山梨酯注射液２０ｍｇ加于５％葡萄糖液５００ｍＬ中静脉滴注，ｑｄ，连用１４ｄ。另外５０例（男性３５例，女性１５例；年龄６４±８ａ）以德国进口硝酸异山梨酯注射液２０ｍｇ加入５％葡萄糖液５００ｍＬ中静脉滴注，ｑｄ，连用１４ｄ。结果：国产组临床总有效率为９４．１％，心电图总有效率为４８．０％，进口组则依次为９６％与５２％；组间比较，Ｐ值均＞０．０５。该药尚有扩张血管、降低血压、减低心肌氧耗，改善左室功能等作用。结论：本药的疗效和作用与进口硝酸异山梨酯注射液相近。     

Ivabradine: recent and potential applications in clinical practice

INTRODUCTION: published data indicate that heart rate is an independent strong predictor of cardiovascular and all-cause mortality in men and women of all ages, with and without cardiovascular disease, including atherosclerosis, ventricular arrhythmias, and left ventricular dysfunction. Ivabradine is a pure heart-rate-lowering agent with well-documented antianginal and anti-ischemic properties comparable to well-established anti-anginal agents. AREAS COVERED: this short review explores recent results with ivabradine, a new medication that lowers heart rate by selectively inhibiting the I (f) current. This review also describes future potential applications. EXPERT OPINION: measurement of heart rate represents an important component of the assessment of patients with coronary artery disease and chronic heart failure, and should be viewed in the same light as other risk factors, because a high heart rate has direct detrimental effects not only on myocardial ischemia but also on the progression of atherosclerosis, ventricular arrhythmias and left ventricular function. Ivabradine has anti-ischemic and antianginal efficacy equivalent to that of β-blockers and calcium channel antagonists in the treatment of chronic stable angina pectoris. Recently ivabradine has been shown to improve cardiac outcomes in stable coronary artery disease and left ventricular systolic dysfunction in patients who have heart rates of ≥ 70 bpm and in patients with stable angina.