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Circadian rhythm of cardiac electrophysiology, arrhythmogenesis, and the underlying mechanisms.

ABSTRACT: Cardiac arrhythmias are a leading cause of cardiovascular death. It has long been accepted that life-threatening cardiac arrhythmias (ventricular tachycardia, ventricular fibrillation, and sudden cardiac death) are more likely to occur in the morning after waking. It is perhaps less well recognized that there is a circadian rhythm in cardiac pacemaking and other electrophysiological properties of the heart. In addition, there is a circadian rhythm in other arrhythmias, for example, bradyarrhythmias and supraventricular arrhythmias. Two mechanisms may underlie this finding: (1) a central circadian clock in the suprachiasmatic nucleus in the hypothalamus may directly affect the electrophysiology of the heart and arrhythmogenesis via various neurohumoral factors, particularly the autonomic nervous system; or (2) a local circadian clock in the heart itself (albeit under the control of the central clock) may drive a circadian rhythm in the expression of ion channels in the heart, which in turn varies arrhythmic substrate. This review summarizes the current understanding of the circadian rhythm in cardiac electrophysiology, arrhythmogenesis, and the underlying molecular mechanisms.

SUBMITTER: Black N

PROVIDER: S-EPMC6520649 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Circadian rhythm of cardiac electrophysiology, arrhythmogenesis, and the underlying mechanisms.

Black Nicholas N D'Souza Alicia A Wang Yanwen Y Piggins Hugh H Dobrzynski Halina H Morris Gwilym G Boyett Mark R MR

Heart rhythm 20180829 2

Cardiac arrhythmias are a leading cause of cardiovascular death. It has long been accepted that life-threatening cardiac arrhythmias (ventricular tachycardia, ventricular fibrillation, and sudden cardiac death) are more likely to occur in the morning after waking. It is perhaps less well recognized that there is a circadian rhythm in cardiac pacemaking and other electrophysiological properties of the heart. In addition, there is a circadian rhythm in other arrhythmias, for example, bradyarrhythm ...[more]

PMID: 30170229

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Project description:OBJECTIVES:This study sought to test the hypothesis that elimination of sites of abnormal repolarization, via epicardial RFA, suppresses the electrocardiographic and arrhythmic manifestations of BrS. BACKGROUND:Brugada syndrome (BrS) is associated with ventricular tachycardia and ventricular fibrillation leading to sudden cardiac death. Nademanee et al. reported that radiofrequency ablation (RFA) of right ventricular outflow tract epicardium significantly reduced the electrocardiogram and arrhythmic manifestations of BrS. These authors concluded that low-voltage fractionated electrogram activity and late potentials are caused by conduction delay within the right ventricular outflow tract and that the ameliorative effect of RFA is caused by elimination of this substrate. Szel et al. recently demonstrated that the abnormal electrogram activity is associated with repolarization defects rather than depolarization or conduction defects. METHODS:Action potentials (AP), electrograms, and pseudoelectrocardiogram were simultaneously recorded from coronary-perfused canine right ventricular wedge preparations. Two pharmacological models were used to mimic BrS genotype: combination of INa blocker ajmaline (1 to 10 ?M) and IK-ATP agonist pinacidil (1 to 5 ?M); or combination of Ito agonist NS5806 (4 to 10 ?M) and ICa blocker verapamil (0.5 to 2 ?M). After stable induction of abnormal electrograms and arrhythmic activity, the preparation was mapped and epicardial RFA was applied. RESULTS:Fractionated low-voltage electrical activity was observed in right ventricular epicardium but not endocardium as a consequence of heterogeneities in the appearance of the second upstroke of the epicardial AP. Discrete late potentials developed as a result of delay of the second upstroke of the AP and of concealed phase 2 re-entry. Epicardial RFA of these abnormalities normalized Brugada pattern and abolished arrhythmic activity, regardless of the pharmacological model used. CONCLUSIONS:Our results suggest that epicardial RFA exerts its ameliorative effect in the setting of BrS by destroying the cells with the most prominent AP notch, thus eliminating sites of abnormal repolarization and the substrate for ventricular tachycardia ventricular fibrillation.

Dataset Information

Circadian rhythm of cardiac electrophysiology, arrhythmogenesis, and the underlying mechanisms.

Publications

Circadian rhythm of cardiac electrophysiology, arrhythmogenesis, and the underlying mechanisms.

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