Medikamentöse Therapie tachykarder Herzrhythmusstörungen

Zusammenfassung Tachykarde Herzrhythmusstörungen lassen sich im wesentlichen auf eine Störung der Erregungsbildung — Fokusgenese — oder der Erregungsleitung — begünstigend für eine Kreiserregung —, zurückführen. Antiarrhythmika wirken diesen beiden entscheidenden Störungen entgegen. Auf Grund ihrer Hauptwirkung auf das Aktionspotential isolierter Herzmuskelzellen in therapeutischen Dosen lassen sich die Antiarrhythmika in 4 Gruppen einteilen. Beim Menschen läßt die schwerpunktmäßige Beeinflussung der Erregungsleitung in den verschiedenen Anteilen des Erregungsleitungssystems Anwendungsschwerpunkte begründen und Nebenwirkungen voraussagen. Die Antiarrhythmikawirkung auf die elektrophysiologischen Vorgänge am kranken menschlichen Herzen sind bisher noch unzureichend untersucht, so daß für die klinische Therapie letztlich die Empirie, d.h. die systematische therapeutische Anwendung entscheidet. Für die wichtigsten Antiarrhythmika haben sich so bevorzugte Indikationen ergeben. Unter bestimmten Voraussetzungen ist in der Klinik aber auch eine pathogenetisch differenzierende Therapie möglich, wenn auf Grund der bekannten spezifischen Wirkung eines Antiarrhythmikums ein Rückschluß auf die Pathogenese möglich wird; so u.a. beim Ansprechen auf Kalziumantagonisten, Typ Verapamil, die offenbar spezifisch auf sogenannte slow response Aktionspotentiale wirken. Vorbestehende TU-Abnormitäten im EKG weisen auf eine inhomogene Repolarisation als prädisponierenden Faktor für ventrikuläre Tachykardien durch Kreiserregung hin. Beim akuten Herzinfarkt kommt es zu wechselnden elektrophysiologischen Voraussetzungen für die Entstehung von Herzrhythmusstörungen, die eine therapeutische Beeinflussung durch ein einziges Antiarrhythmikum unwahrscheinlich erscheinen lassen. In der Hospitalphase ist eine ausreichend dosierte prophylaktische Gabe von Lidokain sinnvoll, in der prähospitalen Phase ohne Überwachungsmöglichkeit jedoch von zweifelhaftem Wert. Die prophylaktische Gabe von Betarezeptorenblockern kann in der posthospitalen Nachbehandlungsphase das Risiko des plötzlichen Herztodes um 50% senken. Auch bei anderen Risikopatienten mit ventrikulären Herzrhythmusstörungen ist eine konsequente antiarrhythmische Behandlung notwendig.     

阵发性心房颤动患者心房复极离散度的研究

目的　通过记录阵发性心房颤动 (房颤 )患者心房单相动作电位 (MAP) ,分析心房复极离散度与房颤发生的关系。方法　特发性阵发性房颤患者与无自发房颤病史的阵发性室上性心动过速患者各 1 5例 ,均接受心内电生理检查和 /或导管射频消融治疗。两根 MAP电极于右心房共取 4～ 1 0个不同部位进行同步的窦性心律基础刺激 (S1)及期前刺激 S2 时的 MAP记录。测量、计算心房复极离散度(RTd)及动作电位时限和局部冲动时间的离散度 (APDd、ATd)。　结果　窦性心律时房颤组最大 RTd显著大于对照组 (1 2 3 .69± 54.67) ms比 (64 .2 5± 2 3 .2 9) ms,(P<0 .0 1 )。其差异主要来源于 APDd(1 1 5.0 0± 4 6.90 ) ms比 (57.56± 3 3 .57) ms,(P<0 .0 1 ) ,ATd差异无显著性。随 S1、S2 的加入 ,各组局部激动时间和离散度逐渐增大 ,而动作电位时限逐渐缩短 ,且房颤组的这种改变程度显著大于对照组。在S1时无房颤发生 ,加入期前刺激时 ,大多数房颤组患者均多次诱发出短阵房颤。其诱发率及次数均显著高于对照组。　结论　研究结果表明 ,MAP记录技术是临床观察、分析心房复极离散度及其在阵发性房颤中的作用的较佳方法。心房复极离散度的增加是阵发性房颤发生的重要因素。期前刺激时动作电位时限的缩短和离散以及传导障碍在     

Beat-to-beat repolarisation variability in body surface electrocardiograms

The repolarisation variability in body surface electrocardiograms has been evaluated by beat-to-beat QT interval variability. Interpolated R-peak time and template T-wave matching algorithms were used to determine the characteristic time points of the R-wave and T-wave, respectively. The T-wave time can be determined accurately and robustly by searching for the best match between a template T-wave and measured T-waves. The authors studied 5 min multichnnel ECG recordings (35 channels) measured in 20 healthy subjects. A QT variability of 2.24±0.79 ms was obtained (1.15±0.30 ms, if linear detrend was used), which is significantly lower than that reported in several other studies. To explore this discrepancy, the sensitivity of the template matching algorithm to periodic and random noise on the ECG was estimated by a simulation study. The results showed that the repolarisation variability depended on selection of the appropriate lead, the signal-to-noise ratio and the effectiveness of baseline correction. Lead II of a standard 12-lead ECG is a reasonable choice for QT variability analysis; however, precordial leads V3-V6 could be better with regard to the amplitude of the T-wave. Poor signal-to-noise ratios can lead to unrealistic values for repolarisation variability.     

Coronary artery disease diagnosis based on exercise electrocardiogram indexes from repolarisation,depolarisation and heart rate variability

Several indexes have been reported to improve the accuracy of exercise test electrocardiogram (ECG) analysis in the diagnosis of coronary artery disease (CAD), compared with the classical ST depression criterion. Some of them combine repolarisation measurements with heart rate (HR) information (such as the so-called ST/HR hysteresis); others are obtained from the depolarisation period (such as the Athens QRS score); finally, there are heart rate variability (HRV) indexes that account for the nervous system activity. The aim of this study was to identify the best exercise ECG indexes for CAD diagnosis. First, a method to automatically estimate repolarisation and depolarisation indexes in the presence of noise during a stress test was developed. The method is divided into three stages: first, a preprocessing step, where QRS detection, filtering and baseline beat rejection are applied to the raw ECG, prior to a weighted averaging secondly, a post-processing step in which potentially noisy averaged beats are identified and discarded based on their noise variance; finally, the measurement step, in which ECG indexes are computed from the averaged beats. Then, a multivariate discriminant analysis was applied to classify patients referred for the exercise test into two groups: ischaemic (positive coronary angiography) and low-risk (Framingham risk index<5%). HR-corrected repolarisation indexes improved the sensitivity (SE) and specificity (SP) of the classical exercise test (SE=90%, SP-79% against SE=65%, SP=66%). Depolarisation indexes also achieved an improvement over ST depression measurements (SE=78%, SP=81%). HRV indexes obtained the best classification results in our study population (SE=94%, SP=92%) by means of the very high-frequency power (VHF) (0.4–1 Hz) at stress peak.     

Orange flavonoid hesperetin modulates cardiac hERG potassium channel via binding to amino acid F656

Background and aimsHesperetin belongs to the flavonoid subgroup classified as citrus flavonoids and is the main flavonoid in oranges. A high dietary intake of flavonoids has been associated with a significant reduction in cardiovascular mortality. HERG potassium channels play a major role in cardiac repolarisation and represent the most important pharmacologic target of both antiarrhythmic and proarrhythmic drugs.Methods and resultsWe used the two-microelectrode voltage-clamp technique to analyse inhibitory effects of hesperetin on hERG potassium channels heterologously expressed in Xenopus oocytes. Hesperetin blocked hERG potassium channels in a concentration dependent manner. Onset of block was fast and completely reversible upon wash-out. There was no significant effect of hesperetin on channel kinetics. Affinity of hesperetin to mutant F656A hERG channel was significantly decreased compared to WT hERG, indicating a binding site in the channel pore cavity. In contrast, affinity of hesperetin to Y652A hERG was not different from the affinity to WT hERG.ConclusionWe found an antagonist of cardiac hERG channels that modulates hERG currents by accessing the aromatic pore binding site, particularly amino acid phe-656. Regarding high hesperetin concentrations found in oranges and the increasing consumption of oranges and orange juice in Europe, potential effects of hesperetin on cardiac electrophysiology in vivo deserve further investigation.     

Evidence of mechanoelectric feedback in the atria of patients with atrioventricular nodal reentrant tachycardia

Objective Patients with atrioventricular nodal reentrant tachycardia (AVNRT) could serve as a clinical model to study the effects of mechanical stretch in the electrical properties of atrial myocardium.Materials and methods We studied 14 patients with AVNRT. Peak, mean and minimal atrial pressures, atrial refractoriness (ERP) in the right atrial appendage and high right atrial lateral wall and monophasic action potential duration at 90% of repolarisation (MAPd90) in the right atrial appendage were assessed during atrial pacing at 500 and 400 ms and after 2 min of pacing at the tachycardia cycle length. Measurements were repeated from the same positions after ventricular pacing at the same cycle lengths and after 2 min of tachycardia. Susceptibility to atrial fibrillation (AF) was assessed by noting whether AF was induced during ERP evaluation.Results Atrial pressure showed a statistically significant increase during ventricular pacing compared to baseline. This increase remained substantially unchanged when the tachycardia was induced. A significant reduction in atrial ERP and MAPd90 was also observed during ventricular pacing at all cycle lengths compared to atrial pacing. Two minutes of spontaneous tachycardia were enough to change the atrial ERP and MAPd90 to values significantly lower than those during atrial pacing at the cycle length of tachycardia. During the ERP evaluation AF was induced more often during the tachycardia (28%) than during ventricular (14%) and atrial pacing (0%).Conclusion In AVNRT patients, ventricular pacing and reentrant tachycardia significantly increase right atrial pressures and subsequently shorten ERP and MAPd90, leading to an enhanced propensity for AF.     

How to measure electrocardiographic QT interval in the anaesthetized rabbit

Many drugs prolong QT or QU intervals [QT(U)] in the electrocardiogram (ECG), and this may be associated with the generation of drug-induced torsades de pointes. Therefore, it is essential to assess the ability of the newly developed drugs to prolong QT(U) interval. For this purpose, both in vivo and in vitro rabbit models are frequently used. However, it is very difficult to locate the end of the QT(U) interval in most rabbit ECGs when repolarisation is delayed, as the shape of the T and U waves may be deformed. In addition, as the heart rate of the rabbit is very high, the T (or U) wave may overlap the P wave or even the QRS complex of the following sinoatrial beat. In these circumstances, application of the “extrapolation method” makes it possible to determine the length of the QT(U) interval. This article describes the extrapolation method, shows ECG examples of typical T and U waves in the anaesthetized rabbit, and makes an attempt to provide a useful guide for researchers to measure reliably and reproducibly the duration of the QT(U) interval in rabbit studies.