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AimsEnhanced sympathetic activity during acute ischaemia is arrhythmogenic, but the underlying mechanism is unknown. During ischaemia, a diastolic current flows from the ischaemic to the non-ischaemic myocardium. This 'injury' current can cause ventricular premature beats (VPBs) originating in the non-ischaemic myocardium, especially during a deeply negative T wave in the ischaemic zone. We reasoned that shortening of repolarization in myocardium adjacent to ischaemic myocardium increases the 'injury' current and causes earlier deeply negative T waves in the ischaemic zone, and re-excitation of the normal myocardium. We tested this hypothesis by activation and repolarization mapping during stimulation of the left stellate ganglion (LSG) during left anterior descending coronary artery (LAD) occlusion.Methods and resultsIn nine pigs, five subsequent episodes of acute ischaemia, separated by 20 min of reperfusion, were produced by occlusion of the LAD and 121 epicardial local unipolar electrograms were recorded. During the third occlusion, left stellate ganglion stimulation (LSGS) was initiated after 3 min for a 30-s period, causing a shortening of repolarization in the normal myocardium by about 100 ms. This resulted in more negative T waves in the ischaemic zone and more VPBs than during the second, control, occlusion. Following the decentralization of the LSG (including removal of the right stellate ganglion and bilateral cervical vagotomy), fewer VPBs occurred during ischaemia without LSGS. During LSGS, the number of VPBs was similar to that recorded before decentralization.ConclusionLSGS, by virtue of shortening of repolarization in the non-ischaemic myocardium by about 100 ms, causes deeply negative T waves in the ischaemic tissue and VPBs originating from the normal tissue adjacent to the ischaemic border.

BackgroundDispersion in ventricular repolarization is relevant for arrhythmogenesis.ObjectiveThe purpose of this study was to determine the spatiotemporal effects of sympathetic stimulation on ventricular repolarization.MethodsIn 5 anesthetized female open-chest pigs, ventricular repolarization was measured from the anterior, lateral, and posterior walls of the left ventricle (LV) and right ventricle using up to 40 transmural plunge needles (4 electrodes each) before and after left stellate ganglion stimulation (LSGS) and right stellate ganglion stimulation. In addition, LSGS was performed in 3 pigs (2 male, 1 female) before and after verapamil (5-10 mg/h) administration.ResultsLSGS yielded a biphasic response in repolarization in the lateral and posterior walls of the LV, with prolongation at ∼5 seconds (10 ± 1.5 ms) and shortening at 20-30 seconds of stimulation (-28.9 ± 4.4 ms) during a monotonic pressure increase. While the initial prolongation was abolished by verapamil, late shortening was augmented. Sequential transections of the vagal nerve and stellate ganglia augmented repolarization dispersion responses to LSGS in 2 of 5 hearts. An equal pressure increase by aortic occlusion resulted in a homogeneous shortening of repolarization in the LV, and the effects were smaller than those during LSGS. Right stellate stimulation shortened repolarization mainly in the anterior LV wall, but the effects were smaller than those of LSGS.ConclusionLSGS first prolongs (through the L-type calcium current) and then shortens repolarization. The effect of LSGS was prominent in the posterior and lateral, not the anterior, LV walls.

Background: Torsades de pointes arrhythmia is a potentially lethal polymorphic ventricular tachyarrhythmia (pVT) in the setting of long QT syndrome. Arrhythmia susceptibility is influenced by risk factors modifying repolarization.Objective: The purpose of this article was to characterize repolarization duration and heterogeneity in relation to pVT inducibility and maintenance.Methods: Sotalol was infused regionally or globally in isolated Langendorff blood-perfused pig hearts (N = 7) to create repolarization time (RT) heterogeneities. Programmed stimulation and epicardial activation and repolarization mapping were performed. The role of RT (heterogeneities) was studied in more detail using a computer model of the human heart.Results: pVTs (n = 11) were inducible at a critical combination of RT and RT heterogeneities. The pVT cycle lengths were similar in the short and long RT regions. Short-lasting pVTs were maintained by focal activity while longer-lasting pVTs by reentry wandering along the interface between the 2 regions. Local restitution curves from the long and short RT regions crossed. This was associated with T-wave inversion at coupling intervals at either side of the crossing point. These experimental observations were confirmed by the computer simulations.Conclusion: pVTs are inducible within a critical range of RT and RT heterogeneities and are maintained by reentry wandering along the repolarization gradient. Double potentials localize at the core of the reentrant circuit and reflect phase singularities. RT gradient and T waves invert with short-coupled premature beats in the long RT region as a result of the crossing of the restitution curves allowing reentry initiation. [ABSTRACT FROM AUTHOR]

The left ventricular ( LV) coronary-perfused canine wedge preparation is a model commonly used for studying cardiac repolarization. In wedge studies, transmembrane potentials typically are recorded; whereas, extracellular electrical recordings are commonly used in intact hearts. We compared electrically measured activation recovery interval ( ARI) patterns in the intact heart with those recorded at the same location in the LV wedge preparation. We also compared electrically recorded and optically obtained ARIs in the LV wedge preparation. Five Langendorff-perfused canine hearts were paced from the right atrium. Local activation and repolarization times were measured with eight transmural needle electrodes. Subsequently, left ventricular coronary-perfused wedge preparations were prepared from these hearts while the electrodes remained in place. Three electrodes remained at identical positions as in the intact heart. Both electrograms and optical action potentials were recorded (pacing cycle length 400-4000 msec) and activation and repolarization patterns were analyzed. ARIs found in the subepicardium were shorter than in the subendocardium in the LV wedge preparation but not in the intact heart. The transmural ARI gradient recorded at the cut surface of the wedge was not different from that recorded internally. ARIs recorded internally and at the cut surface in the LV wedge preparation, both correlated with optically recorded action potentials. ARI and RT gradients in the LV wedge preparation differed from those in the intact canine heart, implying that those observations in human LV wedge preparations also should be extrapolated to the intact human heart with caution. [ABSTRACT FROM AUTHOR]

Aims: The aim of this study was to evaluate the effect of increase in left ventricular (LV) pressure on repolarization and activation-recovery intervals. Methods and results: Six pig hearts were Langendorff-perfused. A compliant liquid-filled balloon, connected with a pressure transducer, inserted through the mitral orifice, could be filled until the required LV systolic pressurewas obtained. Agrid of 121 electrodes (11 × 11; 5 mminterelectrode distance)was sutured on the LV freewall. Ventricular pacing at 600 ms and at 400 or 450 ms was either performed from the LV wall or from the ventricular septum. Under all these four conditions, the pressure wave occurred at the same moment relative to the onset of the QRS complex. Consequently, the time relation between local repolarization and the pressurewave differed between the various pacing sites. Repolarization times (RTs) at a cycle length (CL) of 600 ms were prolonged by increased pressure. With stimulation from the LV, when the pressure wave coincides with the action potentials (APs) late in their phase (sites with relatively early repolarization), an increase in pressure from 0 to 100 mmHg delayed repolarization more than with stimulation from the septum, when the pressure wave occurs at a relatively earlier phase of the AP(sites with relatively late repolarization). At pacing atCL 400/450 ms, an increase in pressure caused RT prolongation at the LV free wall during LV stimulation, but less RT prolongation or even shortening during septal stimulation. Conclusion The effect of increased LV pressure is synchronization of repolarization. [ABSTRACT FROM AUTHOR]

Background Long QT2 (LQT2) syndrome is characterized by bifid (or notched) T waves, whose mechanism is not understood. Objective The purpose of this study was to test whether increased interventricular dispersion of repolarization induces bifid T waves. Methods We simultaneously recorded surface ECG and unipolar electrograms at baseline and after dofetilide in a canine model of dofetilide-induced LQT2 (6 male mongrel dogs). Standard ECG variables, T-wave duration, and moments of peaks of bifid T waves (Tp1 and Tp2) were correlated with moments of local repolarization. Epicardial electrograms were recorded over the left ventricular (LV) and right ventricular (RV) anterior walls (11 × 11 electrode grid, 5-mm interelectrode distance). In 5 of the 6 hearts, we also recorded intramural unipolar electrograms (n = 4–7 needles per heart). In each unipolar recording, we determined activation time, repolarization time (RTs), and activation–recovery interval. In addition, we studied RT response to heart rate changes. Results Dofetilide prolonged QT and QTc, induced bifid T waves in 4 of 6 animals, and prolonged RT heterogeneously in LV and RV, resulting in increased interventricular and LV intraventricular RT dispersion. Dofetilide did not induce a disparate response in activation–recovery interval across the transmural axis. Dofetilide-induced separation of RT across the RV–LV interface concurred with the moments of T-wave peaks. Dofetilide-induced steepening of restitution slopes was larger in LV than RV. Conclusion Dofetilide-induced bifid T waves result from interventricular RT dispersion. [ABSTRACT FROM AUTHOR]

Heterogeneous distribution of electrophysiological behavior across the heart is essential for normal cardiac function. If this heterogeneity becomes excessive it may contribute to arrhythmogenesis and sudden cardiac death. Controversy exists regarding the localization of activation and repolarization gradients in the diseased heart and how these heterogeneities contribute to arrhythmogenesis. In this review we focus on the genesis and existence of transmural heterogeneity in activation and repolarization. We will describe a possible embryonic origin of these heterogeneities and address the question how heterogeneities contribute to the genesis of the electrocardiogram and how they may cause reentrant arrhythmias. This review subsequently concentrates on several pathologies in which transmural heterogeneities are thought to play a role. [ABSTRACT FROM AUTHOR]