地尔硫注射液治疗老年心力衰竭伴快速房性心律失常的疗效和安全性研究

目的观察老年中度和重度心力衰竭伴快速房性心律失常(包括心房颤动和心房扑动)患者静脉注射地尔硫控制心室率的有效性和安全性。方法选取NYHAⅢ、Ⅳ级的中、重度心力衰竭伴快速房性心律失常的老年患者,给予地尔硫静脉注射,观察有效率及血压、症状和体征变化。结果85例患者入选,80例(94.1%)患者有效,心室率由用药前的(149.5±18.2)次/分下降至用药结束时的(95.3±17.5)次/分,下降幅度36.2%,平均起效时间(6.3±3.9)分钟,用药前后心室率下降有显著意义(P<0.001)。所有患者血压均有下降但多在正常范围,有5例出现低血压,1例出现Ⅰ度房室传导阻滞伴窦性心动过缓,无1例出现心功能恶化。结论静脉注射地尔硫能迅速有效地控制中重度心力衰竭伴快速房性心律失常的老年患者的快速心室率,而且安全性高。     

Differences in arrhythmogenicity between the canine right ventricular outflow tract and anteroinferior right ventricle in a model of Brugada syndrome

BACKGROUND: The Brugada syndrome is characterized by ST-segment elevation on the ECG, especially in the right precordial leads sensitive to the right ventricular outflow tract (RVOT). OBJECTIVES: The purpose of this study was to evaluate the hypothesis that right ventricular electrophysiologic heterogeneity caused arrhythmogenicity in the Brugada syndrome. METHODS: Action potentials (APs) were mapped on the epicardium of 14 RVOT preparations and on the transmural surfaces of 15 pairs of RVOT and right ventricular anteroinferior (RVAI) preparations isolated from canine hearts. Brugada ECG and arrhythmias were induced with pilsicainide (2.5-12.5 micromol/L), pinacidil (1.25-12.5 micromol/L), and terfenadine (2.0 micromol/L). RESULTS: Low doses of drugs elevated the J-ST segment and induced APs with both short and long action potential durations (APDs) in contiguous RVOT epicardial regions. In addition, APs in the RVOT had a larger phase 1 notch and longer APD than in RVAI. The longest APDs were in the epicardium in RVOT but in the endocardium in RVAI regions. High doses of drugs eliminated the phase 2 dome of the AP and abbreviated APDs in the epicardium but not in endocardium and reduced the epicardial heterogeneity of APs but increased the transmural gradient of APD in 14 (93%) of the RVOT preparations. In contrast, abbreviations of epicardial APDs occurred in only 4 (27%) of the RVAI preparations. Ventricular tachycardia occurred more frequently in the RVOT (47%) than in paired RVAI preparations (7%). Blocking the transient outward current reduced the heterogeneity of APs and eliminated arrhythmogenicity in all preparations. CONCLUSION: Compared with the RVAI region, the RVOT has greater electrophysiologic heterogeneity that contributes to arrhythmogenicity in this model of Brugada syndrome.     

Tyramine-Induced cardiac arrhythmias

Five out of 12 physically healthy patients with depression undergoing a tyramine pressor test developed cardiac arrhythmias. These arrhythmias occurred in drug-free patients in three out of 12 infusions following as little as 0.03 mg/kg of tyramine and after moclobemide, a reversible inhibitor of monoamine oxidase-A, in four out of 14 tyramine infusions with as little as 0.04 mg/kg of tyramine. The arrhythmias seen were independent of patient's age and occurred both before and after 30 mmHg elevations in systolic blood pressure. Electrocardiographic abnormalities and arrhythmias seen were a loss of p waves, sinus tachycardia, frequent atrial ectopic beats, atrial premature beats, Wenckebach phenomenon, junctional rhythm, ventricular ectopics, varying QRS configurations, and ventricular bigeminy. Tyramine, both oral and intravenous, caused similar reproducible changes in dogs, though not in rats, mice or guinea pigs. Practical implications are that tyramine pressor testing in humans should be performed cautiously and only with adequate cardiac monitoring and resuscitation facilities at hand. These findings suggest that a normal dietary component can induce serious cardiac arrhythmias, and that a low-tyramine diet may be of value for patients who are susceptible to cardiac arrhythmias.     

Newer aspects of antiarrhythmic drug development: Introduction

Although cardiac arrhythmias remain a serious clinical problem in many patients with heart disease, the exact role of antiarrhythmic drug therapy is currently under intense evaluation. Within the last several years it has become clear that there are significant risks as well as potential benefits associated with existing agents. Ongoing studies in large patient populations should help determine the benefit/risk ratio of traditional therapy. Regardless of the outcome of these trials, current electrophysiological dogma will have to be re-evaluated and newer concepts evolve for drug development to make further progress. The goal of this symposium is to exchange information among basic and clinical investigators so as to facilitate the emergence of novel electrophysiological concepts that will form the basis for future generations of antiarrhythmic drugs.     

Post-ischemic release of nucleosides and oxypurines in isolated rat hearts. Possible involvement of ventricular fibrillation

Summary In isolated perfused rat hearts global ischemia for 2, 5, and 15 min was produced. Depending on the duration of the ischemia, postischemic reperfusion led to the release of adenosine and its catabolites, and to more or less severe ventricular tachyarrhythmias. When ventricular fibrillation occurred, a highly significant increase in the purine release was observed compared with non-fibrillating hearts. Prevention of fibrillation by antiarrhythmic drugs decreased the purine release in a highly significant way. After only 2 min of ischemia, reperfusion did not lead to ventricular fibrillation. Electrical induction of fibrillation during the reperfusion in these hearts provoked the release of very high amounts of the purine compounds. A similar effect of electrically-induced fibrillation was also obtained in hearts without a previous ischemic period. The findings suggest that ventricular fibrillation is able to induce the release of purine derivatives from the heart.     

Intravenous nitroglycerin suppresses exercise-induced arrhythmias in patients with ischaemic heart disease: implications for long-term treatment

We studied 20 patients with ischaemic heart disease, who consistentlydeveloped complex ventricular arrhythmias during exercise testing.Treadmill exercise was performed twice, both during the placeboinfusion and then during intravenous administration of nitroglycerin,titrated to reduce systolic blood pressure by 10 mmHg. Exerciseduration in those administered placebo was 7·8 ±1·7 and 7·9 ± 1·5 min, respectively(ns): angina developed in five patients and ischaemic ST changesin 10. In those administered nitroglycerin, exercise durationincreased to 8·4 ± 2 mm (P<0·05). DiagnosticST segment depression was observed in only two patients andonly one had angina. Ventricular arrhythmias, consistently presentduring both tests on those administered placebo, were dramaticallyreduced by nitroglycerin in all 20 patients. There were 455(mean 35·8± 16·8) and 4l8 (mean 34·4±11·1)ventricular ectopic beats in the two exercise tests on thoseadministered placebo and 11 in those receiving the nitroglycerininfusion (mean 0·6 ± 0·1 (P<0·001).There were 28 and 29 couplets in those receiving placebo (ns)and none in those receiving nitroglycerin (P<0·001).Ventricular tachycardia was present in six and eight patientswho received placebo but in none in those administered nitroglycerin(P<0·001). Abolition of exercise-induced arrhythmiaswas maintained during chronic treatment with oral coronary vasodilators.Prevention of exercise-related arrhythmias by nitroglycerinappears a good indicator of their ischaemic origin and may providevaluable information for long-term prophylaxis with oral vasodilators,thus avoiding antiarrhythmic agents with their potential sideeffects.     

Electrophysiologic mechanisms of ventricular arrhythmias

In this work the electrophysiologic mechanisms of ventricular arrhythmias have been briefly summarized. Ventricular arrhytmias can be caused either by pacemaker activity or by reentrant excitation. Enhancement of normal automaticy can generate a parasystolic rhythm in normal fibers. Abnormal automaticity may arise fom fibers in which maximum diastolic potential has been reduced by a variety of interventions. Triggered activity is caused by either an early (EAD) or delayed (DAD) afterdepolarization and requires a prior normal action potential for initiation. While there is growing evidence that EAD-induced triggered activity plays a significant role in the Long QTU syndrome and Torsade de Pointes, no clinical arrhythmias has definitely been ascribed to DADs, although DADs have been recorded in man after acute digoxin intoxication.Ventricular arrhytmias can be also caused by reentrant excitation, which can be subdivided into reflection or circus movement reentry (CMR). In the reflection model impulses in both directions are transmitted over the same pathway. In the CMR three models can be differentiated: the ring model, which requires a fixed anatomical obstacle; the figure-eight model and the leading circle model, where functional rather than fixed anatomical obstacles are involved.Abbreviations AV atrio-ventricular - CMR circus movement reentry - DAD delayed afterdepolarization - EAD early afterdepolarization - ECG electrocardiogram - LV left ventricle - MAP monophasic action potential - MF muscle fiber - PF Purkinje fiber - RV right ventricle - TdP Torsade de Pointes     

氨乙基异硫脲对大鼠离体心脏冠脉结扎后再灌期心律失常与细胞动作电位的作用

用Langendorff方法与微电极技术研究自由基清除剂氨乙基异硫脲(AET)对离体大鼠心脏冠脉结扎后再灌期心律失常与细胞动作电位的作用。AET(0.001～1mmol/L)使室颤和室速发生率明显下降,使正常窦性心律时间增加。浓度为0.01～1mmol/L的AET可使不可逆室颤发生率下降为零。冠脉阻塞再灌损伤使缺血中心区心肌动作电位波形异常,APA,RP,V_(max)各参数下降。AET(0.1mmol/L)可使异常波形动作电位显著减少。