Background-Enhanced sympathetic activity facilitates complex ventricular arrhythmias and fibrillation. The restitution properties of action potential duration (APD) are important determinants of electrical stability in the myocardium. Steepening of the slope of APD restitution has been shown to promote wave break and ventricular fibrillation. The effect of adrenergic stimulation on APD restitution in humans is unknown. Methods and Results-Monophasic action potentials were recorded from the right ventricular septum in 18 patients.Standard APD restitution curves were constructed at 3 basic drive cycle lengths (CLs) of 600, 500, and 400 ms under resting conditions and during infusion of isoprenaline (15 patients) or adrenaline (3 patients). The maximum slope of the restitution curves was measured by piecewise linear regression segments of sequential 40-ms ranges of diastolic intervals in steps of 10 ms. Under control conditions, the maximum slope was steeper at longer basic CLs; eg, mean values for the maximum slope were 1.053Ϯ0.092 at CL 600 ms and 0.711Ϯ0.049 at CL 400 ms (ϮSEM). Isoprenaline increased the steepness of the maximum slope of APD restitution, eg, from a maximum slope of 0.923Ϯ0.058 to a maximum slope of 1.202Ϯ0.121 at CL 500 ms. The effect of isoprenaline was greater at the shorter basic CLs. A similar overall effect was observed with adrenaline. Conclusions-The

SUMMARYSudden unexpected death in epilepsy (SUDEP) is probably caused by periictal cardiorespiratory alterations such as central apnea, bradyarrhythmia, and neurogenic pulmonary edema. These alterations may occur in people with epilepsy and vary in duration and severity. Seizurerelated ventricular tachyarrhythmias have also been hypothesized to be involved in SUDEP, but compelling evidence of these, or of predisposition to these, is lacking. Ventricular tachyarrhythmias are facilitated by pathologic cardiac repolarization. Electrocardiography (ECG) indicators of pathologic cardiac repolarization, such as prolongation or shortening of QT intervals as well as increased QT dispersion, are established risk factors for life-threatening tachyarrhythmia and sudden cardiac death (SDC). Abnormalities in cardiac repolarization have recently been described in people with epilepsy. Importantly, periictal ventricular tachycardia and fibrillation have also been reported in the absence of any underlying cardiac disease. Therefore, pathologic cardiac repolarization could promote SCD in people with epilepsy and could be one plausible cause for SUDEP.Herein, we review abnormal cardiac repolarization in people with epilepsy, describe the putative contribution of antiepileptic drugs, and discuss the potential role of pathologic cardiac repolarization in SUDEP. Based on these, measures to reduce the risk of or prevent SUDEP may include antiarrhythmic medication and implantation of cardiac combined pacemaker-defibrillator devices.

Transmural repolarisation differences within the ventricular wall of the human heart were absent at cycle lengths within the physiological range but also during prolonged cycles. During early (global) ischaemia repolarisation changed equally in subepicardial and subendocardial regions and transmural homogeneity of repolarisation was preserved.

This review examines current knowledge of the effects of higher brain centres and autonomic control loops on the heart with particular relevance to arrhythmogenesis. There is now substantial evidence that higher brain function (cortex), the brain stem and autonomic nerves affect cardiac electrophysiology and arrhythmia, and that these may function as an interactive system. The roles of mental stress and emotion in arrhythmogenesis and sudden cardiac death are no longer confined to the realms of anecdote. Advances in molecular cardiology have identified cardiac cellular ion channel mutations conferring vulnerability to arrhythmic death at the myocardial level. Indeed, specific channelopathies such as long QT syndrome and Brugada syndrome are selectively sensitive to either sympathetic or vagal stimulation. There is increasing evidence that afferent feedback from the heart to the higher centres may affect efferent input to the heart and modulate the cardiac electrophysiology. The new era of functional neuroimaging has identified the central neural circuitry in this brain-heart axis. Since precipitants of sudden fatal arrhythmia are frequently environmental and behavioural, central pathways translating stress into autonomic effects on the heart might be considered as therapeutic targets. These brain-heart interactions help explain the apparent randomness of sudden cardiac events and provide new insights into future novel therapies to prevent sudden death.

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forward to collaborating with Dr. Solaro in this new position and to welcoming his new editorial team to the journal.The Journal of Molecular and Cellular Cardiology publishes work advancing knowledge of the mechanisms responsible for both normal and diseased cardiovascular function. To this end papers are published in all relevant areas. These include (but are not limited to): structural biology; genetics; proteomics; morphology; stem cells; molecular biology; metabolism; biophysics; electrophysiology; pharmacology and physiology. Papers are encouraged with both basic and translational approaches. The journal is directed not only to basic scientists but also to clinical cardiologists who wish to follow the rapidly advancing frontiers of basic knowledge of the heart and circulation.

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We developed an algorithm to calculate a reentry vulnerability index from intervals between local repolarization and activation. The algorithm accurately identified the region of reentry in 2 animal models of functional reentry. The clinical application was demonstrated in a patient with VT and identified the area of reentry without the need of inducing the arrhythmia.