Effects of short-term intravenous administration of diltiazem on left ventricular function and coronary hemodynamics in patients with coronary artery disease

The hemodynamic effects of diltiazem were investigated in 15 patients with suspected coronary artery disease undergoing routine cardiac catheterization. Diltiazem was given in a high dose of 500 micrograms/kg over a period of 5 min and measurements made before and after drug administration during spontaneous heart rate and during matched atrial pacing. Spontaneous heart rate did not change (-5%; NS). Left ventricular (LV) systolic pressure decreased 24% (p less than 10(-6)) and LV end-diastolic pressure (LVEDP) did not change (-5%; NS). During coronary blood flow measurement, mean aortic pressure decreased 30% (p less than 10(-6)) as global (coronary sinus) and regional (great cardiac vein) coronary vascular resistance diminished with no change in coronary blood flow. Myocardial oxygen consumption decreased 19% (p less than 0.02). During matched pacing, although no change occurred in calculated systolic isovolumic indexes of contractility, end-systolic pressure-volume index decreased 15% (p less than 0.05). The time constant of isovolumic relaxation assessed by a biexponential model decreased. No net change occurred in either global or regional wall motion. In summary, high-dose diltiazem was administered safely to patients with coronary artery disease. It is concluded that, at this dose, diltiazem acted as a peripheral and coronary vasodilator. Hemodynamic changes consistent with a direct negative inotropic and chronotropic effect of the drug were observed. Myocardial oxygen consumption decreased with no change in coronary blood flow.     

Acute hemodynamic effects of intravenous amiodarone in patients with coronary artery disease

The acute hemodynamic effects of intravenous amiodarone (Cordarone injectable; Labaz) were studied during cardiac catheterization in 16 male patients with coronary artery disease (age range, 38-64 years; mean, 53 years). Amiodarone was administered as a bolus at a dosage of 5 mg/kg bodyweight over a 1-min period. Measurements were made 5, 10, and 15 min thereafter. The drug had little effect on heart rate, aortic pressure, cardiac index, and vascular resistances. There were small and nonsignificant increases in left ventricular end-diastolic pressure and end-diastolic volume. The ejection fraction decreased slightly and not significantly. In addition to some increases in pulmonary wedge, pulmonary artery, and right atrial pressures, the significant findings were a 15% decrease in maximal dP/dt and a 12% decrease in left ventricular work. These changes point to a slight negative inotropic effect of amiodarone.     

胺碘酮注射液治疗冠心病室性心律失常

目的探讨胺碘酮治疗冠心病室性心律失常的临床疗效。方法对2009年4月～2011年6月本院门诊及住院确诊的冠心病室性心律失常患者46例,随机分为实验组和对照组各23例。人院后均接受积极的抗心律失常治疗。在接受胺碘酮治疗前1个月,未使用其他抗心律失常药物。实验组给予胺碘酮注射液200mg／次．3次,d,连服1周,然后改为200mg／次,2次,d,连服1周,以后200mg／次,1次,d,以后根据患者病情逐渐减量;对照组口服普罗帕酮150mg／次,3次／d。两组患者均维持治疗2个月,对比两组的临床治疗效果。结果实验组23例患者中。显效12例,有效9例,无效2例,总有效21例,总有效率为90．30％;对照组23例患者中,显效8例,有效7例,无效8例。总有效15例,总有效率为65．22％;两组总有效率比较,差异有统计学意义（P〈0．05）。未出现严重不良反应。结论胺碘酮治疗冠心病室性心律失常疗效显著,安全可靠。但在临床使用时要严格按照适应证。避免不良反应的发生。     

冠心病合并严重室性心律失常临床分析

目的探讨冠心病合并严重室性心律失常的治疗方法。方法对108例冠心病合并严重室性心律失常患者的临床资料进行分析。结果 108例患者中,治疗效果明显者62例,有所进展者38例,医治无效并最终死亡8例,治疗有效率为92.59%。结论威胁冠心病合并严重室性心律失常患者生命安全的主要是急性心肌梗死与合并高血压左心室肥厚。因此,要有针对性开展冠心病合并严重室性心律失常疾病的预防与治疗。     

The haemodynamic effect of intravenous flecainide acetate in patients with coronary artery disease

Flecainide acetate has been shown to be a potent antiarrhythmic agent which is active for more than 8 h, whether given intravenously or orally. However, the negative inotropic effect demonstrated in animal studies could hamper the potential clinical utility of the drug. Ten patients with coronary artery disease but without cardiac failure were given intravenous flecainide (2 mg/kg). Stroke index (SI), left ventricular systolic pressure (LVP), end diastolic pressure (EDP) and LV contractility indices (max dP/dt, VCE 40 mm Hg, peak VCE, Vmax from total pressure (TP] were measured immediately before and 10 min after flecainide, under resting conditions and during atrial pacing with heart rates up to 133 +/- 4.2 beats/min (mean +/- s.e. mean). It is demonstrated that flecainide has a negative inotropic effect, not only under resting conditions, but also less apparently during pacing-induced tachycardia. The effect appears to be dose-related and may result in a reduction of cardiac performance.     

Effect of long-term oral pretreatment with levosimendan on cardiac arrhythmias during coronary artery occlusion in conscious rats

Heart failure is frequently associated with cardiac arrhythmias. The aim of the present study was to investigate the effect of levosimendan, a new cardiotonic drug for the treatment of congestive heart failure, on experimental ischaemic arrhythmias. Acute coronary artery occlusion was produced in conscious rats 7-10 days after placement of ligature around the left main coronary artery. Acute pretreatment with levosimendan (0.2 or 0.6 mg/kg orally 1 h before coronary artery occlusion) did not influence the incidence, onset and duration of arrhythmias. Long-term pretreatment with levosimendan (0.2 or 0.6 mg/kg orally twice a day for 2 weeks) increased the survival rate (50% and 81% vs. 44% in controls) and the number of animals without any arrhythmia (37% and 31% vs. 5% in controls). The present results demonstrate that chronic oral treatment with levosimendan could be beneficial in congestive heart failure and arrhythmias resulting from regional myocardial ischaemia.     

An evaluation of maprotiline intravenous kinetics and comparison of two oral doses

Summary The kinetics of maprotiline have been evaluated in six normal volunteers following rapid intravenous administration of 75 mg. Blood levels could be resolved using a biexponential equation. Mean estimates of half-life, volume of distribution and systemic clearance were 40±15 h, 51.7± 18.01 l/kg and 0.92±0.24 l/kg/h, respectively. Blood/plasma concentrations varied between subjects from 0.77 to 1.64. A comparison of the bioavailability of two oral doses (a 75 mg tablet and three 25 mg tablets) was carried out in the same volunteers. No significant difference was observed between the maprotiline concentrations obtained for the two doses at sampling times up to 26 h. No significant difference was found in the area under the concentration vs. time curves for the two doses. Equivalent bioavailability can be assumed. On the basis of the intravenous injection study, systemic bioavailability averaged 66% and 70% for the 75 mg and three 25 mg tablets respectively.     

Changes in haemodynamics and left ventricular function during intravenous nifedipine infusion with and without additional propranolol in patients with coronary artery disease. A randomized,placebo controlled trial

Summary The haemodynamic effects of a combined intravenous treatment of nifedipine and propranolol in ten patients with coronary artery disease compared to a single treatment with nifedipine or placebo were investigated.Nifedipine infusion resulted in a reduction of left ventricular (LV) afterload and LV volumes with an increase in heart rate and EF and no change of the double product, coronary sinus flow, LV diastolic parameters and dp/dt_max. Addition of propranolol lowers myocardial oxygen demand by reducing heart rate and dp/dt_max together with a sustained afterload reduction with no change in LV volumes and EF.The vasodilatatory action of nifedipine pretreatment balanced the negative effects of acute beta-receptor blockade on LV function and allows the reduction of myocardial oxygen demand without a deterioration of LV function.     

Ranolazine in patients with coronary artery disease

Traditional anti-anginal agents such as beta-blockers and nitrates improve symptoms of cardiac ischemia by affecting either blood pressure or heart rates. Despite aggressive therapy, many patients suffer persistent angina, and optimal therapy is limited by intolerance to traditional agents. Ranolazine, a novel anti-anginal agent that is approved for use in the US, is felt to improve ischemic symptoms by reducing myocardial cellular sodium and calcium overload via inhibition of the late sodium current (I(Na)) of the cardiac action potential. Several Phase-III trials in patients with chronic angina have demonstrated that ranolazine improves exercise tolerance and reduces ischemic symptoms as compared with placebo. In the largest evaluation of ranolazine, the MERLIN-TIMI 36 trial (Metabolic Efficiency with Ranolazine for Less Ischemia in non ST elevation acute coronary syndrome), ranolazine did not reduce the risk of death or recurrent myocardial infarction in patients with non-ST-elevation acute coronary syndromes, but it did improve ischemic symptoms over the subsequent year of therapy. Thus, ranolazine offers clinicians a new therapy in the long-term treatment of patients with chronic angina.     

Ranolazine in patients with coronary artery disease

Traditional anti-anginal agents such as β-blockers and nitrates improve symptoms of cardiac ischemia by affecting either blood pressure or heart rates. Despite aggressive therapy, many patients suffer persistent angina, and optimal therapy is limited by intolerance to traditional agents. Ranolazine, a novel anti-anginal agent that is approved for use in the US, is felt to improve ischemic symptoms by reducing myocardial cellular sodium and calcium overload via inhibition of the late sodium current (I_Na) of the cardiac action potential. Several Phase-III trials in patients with chronic angina have demonstrated that ranolazine improves exercise tolerance and reduces ischemic symptoms as compared with placebo. In the largest evaluation of ranolazine, the MERLIN-TIMI 36 trial (Metabolic Efficiency with Ranolazine for Less Ischemia in non ST elevation acute coronary syndrome), ranolazine did not reduce the risk of death or recurrent myocardial infarction in patients with non-ST-elevation acute coronary syndromes, but it did improve ischemic symptoms over the subsequent year of therapy. Thus, ranolazine offers clinicians a new therapy in the long-term treatment of patients with chronic angina.     

Radionuclide assessment of ventricular function in patients with coronary artery disease: clinical perspective

This paper describes how the clinical applications of radionuclide ventriculography have developed during the last decade. The role of resting radionuclide angiography in the assessment of myocardial infarctions, suspected left ventricular aneurysms, and the assessment of right ventricular function are discussed. Currently exercise radionuclide angiography probably represents the best way of assessing left ventricular function under stress. Extensive experience has been gained with this technique in a large number of centres worldwide. Initially the techniques were compared against coronary arteriography as the gold standard, figures for sensitivity, specificity and predictive value of the test in predicting stenosed coronary arteries were produced. This article points out that the exercise study demonstrates the physiological response of the left ventricle to exercise and not every patient with coronary artery disease can be expected to manifest abnormal physiology. Certain valuable prognostic information may be obtained from the results of the exercise radionuclide studies which may guide cardiologists as to which patients should be treated conservatively and which patients should undergo a prognostic intervention. The techniques are of major value in determining the results of both medical and interventional therapy. Abnormal ventricular function response to exercise is not specific for coronary artery disease however, and the relevance of the study must be analysed in relationship to the population under investigation.     

Pethidine clearance during continuous intravenous infusions in postoperative patients.

1 Pethidine pharmacokinetics in ten female patients during continuous i.v. infusion for 32 h post-surgery have been determined. 2 The blood clearance of pethidine (mean +/- 2.d.) measured directly was 599 +/- 135 ml/min and is in marked contrast to some reported values. 3 Other model-dependent pharmacokinetic parameters were consistent with previously reported values. 4 Pethidine and indocyanine green clearance were correlated but the correlation was mediated through body weight. 5 Pethidine clearance and steady state concentration were predictable retrospectively from linear multivariable equations involving simple physical characteristics of the patient.     

Pharmacokinetics of intravenous bepridil in patients with coronary disease

The pharmacokinetics of intravenous bepridil (1-[2-(N-benzylanilino)-1-(isobutoxymethyl)ethyl]pyrrolidine ) were studied in 16 patients undergoing cardiac catheterization for evaluation of coronary disease, all with normal base-line hemodynamic and renal functions. Ten patients received 3 mg/kg and six patients received 4 mg/kg of bepridil infused over a period of 30 min. Plasma bepridil concentrations were measured by HPLC and analyzed by model-dependent and model-independent methods. The mean (+/- SD) maximum plasma bepridil concentrations at the end of the infusion were 2047 +/- 820 ng/mL (3 mg/kg) and 2478 +/- 1426 ng/mL (4 mg/kg). Postinfusion bepridil concentrations were best described by a two-compartment open model. The model-dependent harmonic mean distribution and elimination half-lives were 1.7 h (range: 1.1-2.2 h) and 19.7 h (range: 8.0-61.9 h), respectively. The harmonic mean elimination half-life from model-independent analysis was 14.9 h (range: 7.4-64.0 h). The arithmetic means of other model-independent kinetic parameters were systemic clearance, 0.524 +/- 0.215 L X kg-1 X h-1; Vd, 15.3 +/- 10.9 L/kg; and Vdss, 10.1 +/- 6.0 L/kg. Model-dependent and model-independent estimates of half-life and clearance agreed reasonably well. Bepridil was well tolerated, effecting little or no change in central hemodynamics or EKG intervals. The extensive distribution and relatively slow clearance of bepridil account for its long elimination half-life. Intravenous bepridil appears to be a safe calcium (II) antagonist that is suitable for once-a-day dosing.     

美托洛尔联合胺碘酮治疗冠心病慢性心力衰竭患者室性心律失常的研究

目的 探讨酒石酸美托洛尔片联合胺碘酮治疗冠心病慢性心力衰竭患者室性心律失常的疗效。方法 选择2013年7月-2017年8月在喀什地区第一人民医院治疗的245例冠心病慢性心力衰竭室性心律失常患者作为研究对象,根据治疗方法的不同分为对照组（100例）与观察组（145例）。对照组给予胺碘酮治疗,观察组在对照组的基础上给予酒石酸美托洛尔片,两组患者均治疗观察3个月。观察两组患者的临床疗效,比较两组治疗前后的心功能指标、QT离散度（QTd）和不良反应情况。结果 治疗后,观察组的总有效率为99.3%,显著高于对照组的89.0%,两组比较差异具有统计学意义（P<0.05）。治疗后,两组左室射血分数显著升高,左房内径显著降低（P<0.05）;且观察组心功能改善情况显著优于对照组（P<0.05）。治疗后,两组QTd均显著降低（P<0.05）,且观察组显著低于对照组（P<0.05）。在治疗期间,两组不良反应发生率分别为2.1%和15.0%,观察组显著低于对照组（P<0.05）。结论 酒石酸美托洛尔片联合胺碘酮治疗冠心病慢性心力衰竭患者室性心律失常具有较好的临床疗效,能改善患者心功能,调节QT离散度,减少不良反应的发生。     

参松养心胶囊在冠心病患者室性心律失常中的疗效观察

目的观察参松养心胶囊在冠心病患者室性心律失常中的疗效。方法选择经过冠状动脉造影检查确诊冠心病合并室性心律失常的86例患者,随机分为两组,一组为参松养心胶囊单药治疗组46例(单药组),一组为参松养心胶囊联合美托洛尔缓释片治疗组(联合组)40例,治疗前后均行动态心电图检查,比较两组患者室性心律失常的改善情况。结果两组间治疗后1周、1个月、3个月疗效比较,均无统计学差异(P0.05)。而各组间在治疗1个月和3个月后疗效比较,均有统计学差异(P0.05)。结论参松养心胶囊具有稳定心肌细胞膜电位作用,能降低冠脉阻力及改善心肌细胞供氧。提示在一定时间内,随着疗程的延长,呈现出更好的疗效。在治疗冠心病患者室性心律失常有重要作用。     

阿托伐他汀对老年冠状动脉严重病变患者左心室功能的影响

目的探讨不同剂量阿托伐他汀对老年冠脉严重病变且未进行血运重建患者左心室功能的影响。方法连续入选40例冠状动脉造影证实血管严重病变但不适于血运重建术或不愿行血运重建术的老年患者,完全随机分为小剂量组（10mg／d）20例、大剂量组（40mg／d）20例,随访1年,检测基础条件下、治疗6个月、治疗12个月时脑利钠肽前体（Pro—BNP）水平,超声心动图测定左心室舒张末期内径（LVEDD）、左心室收缩末期内径（LVESD）、左心室射血分数（LVEF）等参数变化,并测定血脂水平、炎症因子（hs-CRP）、ALT、AST、CPK等指标。结果治疗6个月时,2组Pro—BNP水平下降[小剂量组（1204．44±1117．72）pg／ml,大剂量组（727．07±720．26）pg／m1],LVEF水平升高[小剂量组（59．634-5．59）％,大剂量组（62．08±5．77）％]（均P〈0．05）;治疗1年时,2组心功能均显著改善,包括血浆Pro—BNP水平下降[小剂量组（778．55±1316．33）pg／ml,大剂量组（344．89±303．52）pg／ml]、LVEF升高[小剂量组（61．56±6．60）％,大剂量组（63．49±8．17）％]、左心室内径缩小（P〈0．01）,但2组问比较差异无统计学意义。3个月后2组患者血浆hs—CRP水平明显下降[小剂量组（4．68±2．19）mg／L,大剂量组（4．63±1．91）mg／L]（P〈0．05）,治疗6个月和1年时总胆固醇水平、低密度脂蛋白水平、hs—CRP水平显著下降6个月[小剂量组分别为（2．08±0．41）mmol／L、（3．40±2．10）mg／L;大剂量组分别为（3．50±0．53）mmol／L、（1．88±0．49）mmo]／L、（2．31±1．55）mg／L。1年时小剂量组分别为（3．50±0．40）mmol／L、（1．97±0．45）mmol／L、（2．34±1．61）mg／L,大剂量组分别为（3．42±0．54）mmol／L、（1．77±0．44）mmol／L、（1．58±1．17）mg／L]（P〈0．01）。治疗1年,所有患者无肝功能异常,肌酸激酶无明显增高。结论在冠脉严重病变患者中无论应用大剂量、小剂量阿托伐他汀均可以显著降低血浆hs—CRP、Pro—BNP水平,改善左心室功能,并且未见明显不良反应。     

Effect of glucagon on ventricular arrhythmias after coronary artery occlusion and on ventricular automaticity in the dog

1. In anaesthetized dogs, glucagon (100 mug/kg i.v.), caused a significant increase in heart rate and decrease in mean arterial blood pressure. Ventricular automaticity, as determined by the time to the onset of first vagal escape beat and the number of such indioventricular beats during the 30 s period of vagal stimulation, was not significantly altered.2. In unanaesthetized dogs with ventricular arrhythmias produced by two-stage ligation of the anterior descending branch of the left coronary artery, glucagon (30 and 100 mug/kg i.v.), restored normal sinus rhythm in a few animals. In the remaining dogs, there was a significant reduction in the ventricular ectopic activity.3. The significant positive chronotropic response to glucagon elicited in anaesthetized animals was not observed in conscious dogs whose coronary arteries had been ligated.4. These findings enhance the potential usefulness of glucagon in the treatment of acute myocardial infarction, which may often be associated with disturbances of ventricular rhythm.5. In the light of observations made by other workers, it is suggested that the antiarrhythmic effect of glucagon may be due to movement of potassium ions into the cardiac cell.     

Antiarrhythmic and antifibrillatory action of diltiazem on early and late phase ventricular arrhythmias following coronary artery occlusion and on reperfusion ventricular arrhythmias

The effects of diltiazem on ventricular arrhythmias and ventricular vulnerability for fibrillation, both in the very beginning of myocardial ischemia and in the early stage of myocardial necrosis, were evaluated in 13 mongrel dogs. In part I of the study, repeated coronary occlusions were performed. Time course and extent of ventricular ectopy were continuously recorded, and changes in ventricular fibrillation threshold were assessed, both after coronary artery occlusion and release. In part II, a permanent coronary artery occlusion was performed, and the changes in frequency of ventricular arrhythmias were assessed. Diltiazem displayed strong antiarrhythmic and antifibrillatory effects on early ventricular occlusion arrhythmias. The drop in ventricular fibrillation threshold 5 min after coronary occlusion was significantly attenuated. Following the release of coronary artery obstruction, diltiazem failed to reduce the frequency of ventricular fibrillation immediately after the onset of reperfusion. However, during the early postreperfusion period, the drug was able to accelerate significantly the increase in the ventricular fibrillation threshold. Late phase ventricular arrhythmias were not influenced by the drug even when high doses were applied. The different antiarrhythmic actions of diltiazem on early and late phase ventricular arrhythmias can be assumed to be due to differences in the arrhythmogenesis at the very onset of myocardial ischemia compared to the stage of myocardial necrosis.     

不同剂量氯吡格雷对经皮冠状动脉介入治疗的冠状动脉左主干病变患者的疗效与安全性

目的：评价不同剂量氯吡格雷对经皮冠状动脉介入治疗(PCI)的冠状动脉左主干病变患者的近期疗效和安全性。方法：2006年1月至2010年1月因冠状动脉左主干病变(左主干狭窄＞75％)在北京安贞医院抢救中心接受PCI、年龄≤75岁的患者为研究对象,收集其临床资料进行回顾性分析。根据服用氯吡格雷剂量将患者分为75 mg剂量组(PCI治疗后第1～30天口服氯吡格雷75 mg/d)和150 rmg剂量组(PCI治疗后第1～30天口服氯吡格雷150 mg/d)。记录2组患者PCI治疗前和治疗后1、7、14、30 d 血小板最大聚集率和最大聚集时间,观察2组患者住院期间不良反应的发生情况。结果：共120例PCI治疗后住院患者纳入研究。其中,75 mg剂量组男性46例,女性18例,平均年龄(55±7)岁;150 mg剂量组男性35例,女性21例,平均年龄(50±8)岁。PCI治疗前和治疗后1、7、14、30 d血小板最大聚集率和最大聚集时间,75 mg剂量组分别为84％±18％和(240±48)s、81％±14％和(238±44)s、59％±12％和(210±42)s、48％±10％和(199±40)s、43％±10％和(184±30)s,150 mg剂量组分别为86％±16％和(244±46)s、77％±16％和(239±46)s、51％±11％和(180±41)s、40％±10％和(166±33)s、38％±9％和(159±35)s,治疗后2组患者血小板最大聚集率和最大聚集时间均呈下降趋势,但150 mg剂量组这2项指标均低于75 mg剂量组(均P＜0.01)。2组2项指标治疗后7、14、30 d分别与治疗前、治疗后1 d相比差异均有统计学意义(均P＜0.05);2组血小板最大聚集率治疗后14、30 d与治疗后7 d相比差异有统计学意义(P＜0.05);150 mg剂量组血小板最大聚集率治疗后1 d与治疗前相比差异有统计学意义(均P＜0.05)。2组患者均未出现严重出血、再发心肌梗死、中风等心血管事件。*轻微出血和腹痛、消化不良、便秘、皮疹、头晕、头痛等不良反应发生率(75 mg剂量组12例、18.7％,150 mg剂量组13例、23.1％)组间差异无统计学意义(x2=1.046,P=0.593)。结论：在冠状动脉左主干病变患者经皮冠状动脉介入治疗后的抗血栓治疗中,氯吡格雷150 mg/d和75 mg/d均为有效、安全的剂量,但150 mg/d较75 mg/d能更明显地降低血小板聚集且不增加出血风险,可能更有利于减少PCI治疗后血栓的发生。