心室复极异常与恶性室性心律失常

自1903年Einthoven将心电图应用于临床以来，对心血管疾病的诊断和治疗起了非常重要的作用。尽管已经历了一个世纪的岁月，但对心电图的形成原理并未完全阐明，甚至对心电图的基本波形的形成原理仍有争议。但在临床实践中，对心电现象与临床意义的关联已积累了丰富的经验。例如：人们很早就认识到心电图的异常波往往和猝死相关联。     

天门冬氨酸对心室复极和室性心律失常的影响

目的研究腹腔注射天门冬氨酸(NMDA)对心室复极和室性心律失常诱发的影响。方法将36只成年Wistar大鼠随机分为对照组(CTL组)、NMDA组(N组)、NMDA+NMDA的受体拮抗剂MK-801组(N+M组),分别连续10d腹腔给予生理盐水、NMDA、NMDA+MK-801。记录体表心电图(II导联),并在Langerdorff灌流下行程控电刺激,记录左室前壁基底部(LAB)、前壁心尖部(LAA)、后壁基底部(LPB)和后壁心尖部(LPA)复极过程,测量单向动作电位时程(MAPD)和有效不应期(ERP),及其离散度,计算室性心律失常诱发率和频率阈值。结果与CTL组比较,N组PR间期、QT间期和QTc间期延长,心率增快;左室20%、复极三角和90%的复极时间(MAPD20、triangulation、MAPD90)延长,ERP/MAPD90较小;心室复极离散度增加[COVMAPD90:(0.153±0.017)vs(0.034±0.003),COVERP:(0.242±0.018)vs(0.078±0.009),P均0.01];室性心律失常诱发率增加(100%vs 16.7%,P均0.01)。而MK-801减弱了NMDA对心室复极和室性心律失常诱发的影响。结论慢性注射NMDA将延长心室复极时程,增加复极离散度和室性心律失常的易感性。     

胺碘酮对心室复极波形态影响的临床意义

目的 探讨胺碘酮对心室复极波形态的影响。方法 选择各类心律失常194例按下列剂量与方法口服胺碘酮400－600mg/日,10天后改服200－400mg/日,并重点观察ST－U、H．R、Q－T间期等变化情况。结果 显效144例（74．23％）,有效36例（18．3％）,总有效率92．59％。窦性心动过缓30例（15．46％）,P－R间期延长者10例（5．15％）,连结区逸博节律6例（3．0％）,Q－T间期延长者16例（8．25％）。148例ST－T形态正常者,在应用胺碘酮治疗和维持治疗期间,出现122例（82．43％）心室复极波形态变化。其中ST段水平下移者4例（2．70％）,T波峰值消失40例（27．0％）,平直18例（12．16％）,双峰、双相44例（29．73％）,倒置者8例（5．41％）,U波增大及倒置各4例（5．41％）。结论 胺碘酮导致ST－U形态的改变,考虑为该药影响心室肌复极的延迟及不均衡。     

心脏复极储备异常与恶性室性心律失常

心脏复极异常可导致尖端扭转型室性心动过速和心脏性猝死。复极储备是心脏具有的内源性抗心律失常机制,可用来解释心脏复极异常的程度和心律失常发生的可能性。复极储备降低可发生在多种影响心肌细胞离子电流的病理状况和药物作用下,如各种因素导致外向电流降低和内向电流增加时,这些因素可导致恶性心律失常和心源性猝死的易感性增高。现总结心脏复极储备异常的发生机制及相关心律失常的预防和治疗。     

室内传导延迟病人心室复极时间的测定

为观察室内传导延迟(IVCD)时 Q-T 间期和复极时间变化,测量46例 IVCD 体表心电图的除极和复极时间,并与对照组30例进行比较。结果表明,IVCD 病人的 Q-T、Q-T_c 间期延长,不仅是由于除极时间延长,而且与复极时间延长有关。提出应重视和加强对心室复极时间 J-T、Q-T_c—QRS 间期的研究。     

抗心律失常药物的致心律失常作用

抗心律失常药物的致心律失常作用是指抗心律失常药物在某些患者中应用时,在特定病程中或在特定的临床情况下出现用药前没有的新的心律失常或使原有心律失常更加恶化.有的抗心律失常药致心律失常作用后果严重,如不及时处理可危机生命,增加病死率.因此,在抗心律失常治疗过程中,正确及时识别抗心律失常药的致心律失常作用并采取相应对策有着非常重要的临床意义.     

低血钾患者心室复极时间与复极离散度的临床意义

关于低血钾心室复极时间的确定 (ＱＴ间期还是ＱＵ间期 ) ,国内外尚未统一认识。低血钾的复极离散度少有报道。本文旨在通过一组典型的低血钾患者的心电图 ,测量心室复极时间及复极离散度 ,了解低血钾对心室复极时间影响。一、资料与方法随机选择血清钾在 2 6～ 3 4ｍｍｏｌ/Ｌ之间患者 2 5例 ,男14例 ,女 11例。年龄在 18～ 80岁 ,平均年龄 46岁。其中周期性麻痹 9例 ,电解质紊乱 5例 ,高血压病 3例 ,冠心病 2例 ,肝癌 3例 ,糖尿病酮症酸中毒 2例 ,甲状腺机能亢进 1例。选择 2 5例经临床检查健康人为对照组 ,其年龄、性别与低血钾组无明显…     

阻滞延迟钠电流:治疗心律失常的新曙光

大量临床试验证明,目前应用的抗心律失常药物有很大局限性,可能使器质性心脏病患者心律失常病死率和总病死率增加,针对新的靶点寻找更加安全、有效的药物是抗心律失常药物研究的热点。选择性延迟钠电流阻滞剂在治疗浓度不抑制峰钠电流,不延长或仅有限度的延长动作电位时程或QT间期,可能避免药物致心律失常作用的危险,且对房性和室性心律失常均有效,因而针对抑制延迟钠电流的药物治疗可能是未来抗心律失常治疗的新方向。     

复极后不应期

复极后不应期(Postrepolarization refractoriness)并非是一个全新概念,早在1974年,Gettes就已注意并观察到这一心电现象。近年来,对其研究更加深入,并有了显著进展。[定义]正常心肌或心肌细胞的复极常与其不应期同时结束,但缺血心肌却不如此,即兴奋性的恢复明显滞后于复极结束。顾名思义,在复极完成后,心肌细胞仍处于不应期的时间段即为复极后不应期对心房肌和心室肌均为如此。[复极后不应期的发生]对房室结细胞,复极后不应期属于一种生理现象,并经腺苷介导可以更延长     

心室复极的频率适应性

正常心电活动由心肌除极和复极两部分组成。心室除极指心室肌激动的过程,心电图表现为QRS波。而心室复极指心室肌恢复极化状态的过程,心电图表现为J波、ST段、T波和/或U波。临床上常用QT间期代表心室复极。心室复极异常可引起严重的室性心律失常。例如,长QT综合征,无论是遗传性或     

Prevention of Pazopanib-Induced Prolonged Cardiac Repolarization and Proarrhythmic Effects

Background

Pazopanib (PZP) may induce prolonged cardiac repolarization and proarrhythmic effects, similarly to other tyrosine kinase inhibitors.

Objectives

To demonstrate PZP-induced prolonged cardiac repolarization and proarrhythmic electrophysiological effects and to investigate possible preventive effects of metoprolol and diltiazem on ECG changes (prolonged QT) in an experimental rat model.

Methods

Twenty-four Sprague-Dawley adult male rats were randomly assigned to 4 groups (n = 6). The first group (normal group) received 4 mL of tap water and the other groups received 100 mg/kg of PZP (Votrient^® tablet) perorally, via orogastric tubes. After 3 hours, the following solutions were intraperitoneally administered to the animals: physiological saline solution (SP), to the normal group and to the second group (control-PZP+SP group); 1 mg/kg metoprolol (Beloc, Ampule, AstraZeneca), to the third group (PZP+metoprolol group); and 1mg/kg diltiazem (Diltiazem, Mustafa Nevzat), to the fourth group (PZP+diltiazem group). One hour after, and under anesthesia, QTc was calculated by recording ECG on lead I.

Results

The mean QTc interval values were as follows: normal group, 99.93 ± 3.62 ms; control-PZP+SP group, 131.23 ± 12.21 ms; PZP+metoprolol group, 89.36 ± 3.61 ms; and PZP+diltiazem group, 88.86 ± 4.04 ms. Both PZP+metoprolol and PZP+diltiazem groups had significantly shorter QTc intervals compared to the control-PZP+SP group (p < 0.001).

Conclusion

Both metoprolol and diltiazem prevented PZP-induced QT interval prolongation. These drugs may provide a promising prophylactic strategy for the prolonged QTc interval associated with tyrosine kinase inhibitor use.     

Potential Factors That Affect Electrocardiographic Progression of Interatrial Block

Introduction: Interatrial block (IAB; P wave ≥ 110 ms) is associated with atrial tachyarrhythmias and left atrial electromechanical dysfunction. This subtle abnormality is highly prevalent and may exist as partial (pIAB) or advanced IAB (aIAB). Indeed, theoretically pIAB could progress to aIAB with worsening interatrial conduction over time. However, this has been poorly investigated. We retrospectively appraised this phenomenon and also evaluated the influence of common clinical factors such as coronary artery disease (CAD), hypertension (HTN), and use of antihypertensive medications. Methods: Between January 2003 and June 2004, 27 patients who had aIAB on routine 12‐lead ECGs were identified. Past serial ECGs of each patient were evaluated for evidence of change in IAB type. Medical records of respective patients were then reviewed for HTN, type of antihypertensive medication used, and other common comorbidities. Results: Median progression time from pIAB to aIAB was shorter (42 months; mean ± SD = 39.2 ± 30.5) compared to that of normal P wave (P‐normal) to aIAB (66 months; mean ± SD = 64.2 ± 25.6). Use of angiotensin‐converting enzyme inhibitors (ACEIs) appeared to significantly delay the progression time in patients who progressed from pIAB to aIAB (50.1 ± 28.3 vs 10 ± 10.4 months; P = 0.04). Beta‐adrenergic blocker use alone did not significantly affect either progression time but when used in conjunction with ACEIs, appeared to slow such progression. Conclusion: Progression time from pIAB to aIAB is shorter compared to that of P‐normal to aIAB. Given the consequences of IAB, awareness of such progression could be important for clinicians in anticipating potential sequelae.     

Proarrhythmic Potential of Antimicrobial Agents

Several antiarrhythmic and non-cardiovascular drug therapies including antimicrobial agents have been implicated as the causes for QT interval prolongation, torsades de pointes (TdP) ventricular tachycardia and sudden cardiac death. Most of the drugs that have been associated with the lengthening of the QT interval or development of TdP can also block the rapidly activating component of the delayed rectifier potassium current (IKr) in the ventricular cardiomyocytes. This article presents a review of the current literature on the QT interval prolonging effect of antimicrobials based on the results of the in vitro, in vivo studies and case reports. Our observations were derived from currently available Medline database. As we found, the most frequently QT interval prolonging antimicrobials are erythromycin, clarithromycin, fluoroquinolones, halofantrine, and pentamidine. Almost every antimicrobial-associated QT interval prolongation occurs in patients with multiple risk factors of the following: drug interactions, female gender, advanced age, structural heart disease, genetic predisposition, and electrolyte abnormalities. In conclusion, physicians should avoid prescribing antimicrobials having QT prolonging potential for patients with multiple risk factors. Recognition and appropriate treatment of TdP are also indispensable.     

Quantitative Aspects of Ventricular Repolarization

Introduction: QT dispersion assesses repolarization inhomogeneity on 12-lead standard ECG. However, the implications of the electrical cardiac vector during the repolarization phase (the T wave loop) with the genesis of this phenomenon are unknown. Methods and Results: The aim of this study was to explore conventional 12-lead resting ECG QT dispersion and the corresponding morphology of the spatial three-dimensional (3-D) T wave loop in 25 normals subjects, 30 postmyocardial infarction (Ml) patients, and in 17 individuals with congenital long QT syndrome (LQTS). Standard and XYZ ECG leads were simultaneously digitized (250 Hz) and automatically analyzed. Ventricular repolarization dispersion was estimated by the range (RAN12o) and standard deviation (SD12o) of the 12 rate corrected QTo intervals (between the Q wave onset and the T wave offset). Spatial T wave loops were extracted from XYZ data and analyzed with a 3-D algorithm which provides quantitative parameters related to the loop morphology. All scalar measurements of dispersion were significantly larger in the two pathological populations; however none of them could discriminate post-MI from LQTS groups (RAN12o = 33.3, 61.4, and 62.7 ms respectively, for the three populations). Conversely, a loss of planarity and an increased roundness of the T wave loop were observed in the two pathological groups, with the former effect more pronounced in the LQTS (P = 0.04 compared to post-MI) and the latter in the post-MI group (P = 0.02 compared to LQTS). Furthermore, multiple regression and principal component analyses showed that planarity and roundness are independently involved with QT dispersion. Conclusion: Changes in the morphology of the spatial T wave loop associated with QT dispersion were identified. These changes discriminate different substrates of repolarization inhomogeneity. The use of a 3-D technique to assess repolarization inhomogeneity may bring additional information on the intrinsic nature of this disorder.     

Evolution of Action Potential Propagation and Repolarization in Cultured Neonatal Rat Ventricular Myocytes

INTRODUCTION: Cultured neonatal rat ventricular myocytes (NRVM) reestablish gap junctions as they form synchronously and spontaneously beating monolayers, thus providing a useful model for studying activation and repolarization. METHODS AND RESULTS: We used the multielectrode array data acquisition system with 60 unipolar electrodes to investigate the functional organization of cultured NRVM, by determining propagation and repolarization patterns. Activation maps were constructed from the local activation times at each electrode. During days 3 to 8 in culture, QRS amplitude and dV/dt(max) increased with age. Concomitantly, with the culture maturation, QT interval (representing action potential duration) decreased, and T wave amplitude and slopes of the T wave ascending and descending limbs progressively increased. The changes in conduction velocity were different than those of the electrogram properties, slightly increasing during the first 3 to 5 days and gradually declining toward day 8 in culture. CONCLUSION: Establishment of uniform activation patterns in spontaneously firing or driven myocytes in monolayer cultures is accompanied by organization of activation and repolarization whose evolution appears in concert with that of a mature connexin43 staining pattern. The experimental techniques developed in this study provide useful tools to investigate the complex relations among gap junctions, conduction velocity, and propagation patterns, as well as a means to learn how gap junctional remodeling under pathophysiologic conditions predisposes the myocardium to arrhythmias.     

Shock-Induced Dispersion of Ventricular Repolarization:

Shock-induced Dispersion and VF Induction. Introduction: Shock-induced dispersion of ventricular repolarization (SIDR) caused by an electrical field stimulus has been suggested as a mechanism of ventricular fibrillation (VF) induction: however, this hypothesis has not been studied systematically in the intact heart. Likewise, the mechanism underlying the upper (ULV) and lower (LLV) limit of vulnerability remains unclear.
Methods and Results: In eight Langendorff-perfused rabbit hearts, monophasic action potentials were recorded simultaneously from ten different sites of both ventricles. Truncated biphasic T wave shocks were randomly delivered at various coupling intervals and strengths, exceeding the vulnerable window, ULV, and LLV. SIDR, defined as the difference between the longest and shortest postshock repolarization times, was 64 ± 15 msec for sbocks inducing VF. SIDR was 41 ± 17 msec for shocks delivered above the ULV, and 33 ± 14 and 27 ± 8 msec for shocks delivered 10 msec before and after the vulnerable window, respectively (all P < 0.01 vs VF-inducing shocks). Although SIDR was larger for shocks delivered below the LLV(93 ± 24 msec, P < 0.01 vs VF-inducing shocks), the repolarization extension was significantly smaller for shocks below the LLV (10.3%± 3.9% vs 16.3%± 4.9%, P < 0.01).
Conclusion: SIDR is influenced by the shock timing and intensity. Large SIDR within the vulnerable window and an SIDR decrease toward its borders suggest that SIDR is essential for VF induction. The decrease in SIDR toward greater shock strengths may explain the ULV. Small repolarization extension for shocks below the LLV may explain why these shocks, despite producing large SIDR, fail to induce VF.     

在电压范围测量的心室复极离散

利用单相动作电位 (MAP)技术描述一种在电压范围内测量心室复极空间离散的新方法。 10个均匀分布的MAP电极 ( 2个位于心内膜、8个位于心外膜 )在 8只离体Langendorff灌流兔心脏上同步记录MAP信号。电压范围的复极离散定义为 3相复极期间某一时刻不同部位MAP复极百分比最大与最小值之差。每隔 10ms计算一次电压离散值并以此构建离散曲线。结果 :将测得的复极离散值对复极时间作图得到一条离散曲线 ,其特点为 :离散在复极早期呈逐渐增加的趋势 ,达到峰值后开始下降 ,并在复极晚期降至趋向于零。为检测此方法的实用性 ,我们比较了离散曲线与双相T波电击易损窗的关系后发现 ,易损窗占绝对优势地发生在离散值高的时候 ,并且曲线的峰值与易损窗的左沿密切相关 (r=0 .95 ,P <0 .0 1)。另外 ,心肌缺血使离散曲线高度增加 ,峰值左移 ,同时易损窗的宽度增加。结论 :电压范围的复极离散可为我们提供一种新的测量复极非均一性的手段 ,从而有助于更好地理解心律失常易感性     

Electrocardiographic Quantitation of Heterogeneity of Ventricular Repolarization

Background: QT interval dispersion (QT_d) measured from the surface ECG has emerged as the most common noninvasive method for assessing heterogeneity of ventricular repolarization. Although QT_d correlates with dispersion of monophasic action potential duration at 90% repolarization and with dispersion of recovery time recorded from the epicardium, total T‐wave area, representing a summation of vectors during this time interval, has been shown to have the highest correlation with these invasive measures of dispersion of repolarization. However, recent clinical studies suggest that the ratio of the second to first eigenvalues of the spatial T‐wave vector using principal component analysis (PCA ratio) may more accurately reflect heterogeneity of ventricular repolarization. Methods: To better characterize the ECG correlates of surface ECG measures of heterogeneity of ventricular repolarization and to establish normal values of these criteria using an automated measurement method, the relations of QRS onset to T‐wave offset (QT_od) and to T‐wave peak (QT_pd) dispersion and the PCA ratio to T‐wave area and amplitude, heart rate, QRS axis and duration, and the QT_o interval were examined in 163 asymptomatic subjects with normal resting ECGs and normal left ventricular mass and function. QT_od and QT_pd were measured by computer from digitized ECGs as the difference between the maximum and minimum QT_o and QT_p intervals, respectively. Results: In univariate analyses, a significant correlation was found between the sum of the T‐wave area and the PCA ratio (R =?0.46, P < 0.001), but there was no significant correlation of the sum of T‐wave area with QT_od (R = 0.11, P = NS) or QT_pd (R=0.09, P = NS). There were only modest correlations between QT_od and QT_pd (R = 0.45) and between the PCA ratio and QT_od (R = 0.29) and QT_pd (R = 0.49) (each P < 0.001). In stepwise multivariate linear regression analyses, the PCA ratio was significantly related to the sum of T‐wave area, T‐wave amplitude in aVL, and to female gender (overall R = 0.54, P < 0.001), QT_od correlated only with the maximum QT_o0 interval (R = 0.39, P < 0.001), and QT_pd was related to heart rate and QRS axis (overall R = 0.36, P <0.001). In addition, the normal interlead dispersion of repolarization as measured by QT_od was significantly greater than dispersion measured by QT_od (23.5 ± 11.5 ms vs 18.3 ± 11.2 ms, P < 0.001). Conclusions: These findings provide new information on ECG measures of heterogeneity of repolarization in normal subjects, with a significantly higher intrinsic variability of Q to T‐peak than Q to T‐offset dispersion and only modest correlation between these wo measures. The independent relation of the PCA ratio to the sum of T‐wave area suggests that the PCA ratio may be a more accurate surface ECG reflection of the heterogeneity of ventricular repolarizat on. A.N.E. 2000;5(1):79–87