Circadian determinants of heart rhythm and arrhythmias

This review concerns the mechanisms underlying the circadian rhythm in the electrical activity of the healthy heart. Attention is focussed on the circadian rhythm of the heart rate, the PR interval and the vulnerability to ventricular tachyarrhythmias, because they help to explain the circadian rhythm in the incidence of bradyarrhythmias, atrioventricular block, ventricular fibrillation and sudden cardiac death. Ultimately, all cardiac circadian rhythms are assumed to be extracardiac in origin, driven by a master circadian clock in the suprachiasmatic nucleus (SCN) in the hypothalamus and this review summarises our current understanding of how the SCN is responsible. The oldest explanation is that cardiac circadian rhythms are the result of an acute post-translational regulation of cardiac ion channels by the autonomic nervous system under the control of the SCN - this may be involved, but current evidence is controvertible. There is good evidence that rhythms in the transcription of cardiac ion channels are involved - driven by local circadian clocks in the heart and circadian rhythms in plasma catecholamines and glucocorticoid (all ultimately under the control of the SCN). There is also a plausible suggestion that the core body temperature under the control of the SCN is involved. Understanding the processes involved will potentially highlight new ways of treating cardiac arrhythmias - for example, recently, a glucocorticoid receptor blocker has been shown to prevent the morning increase in ventricular arrhythmia susceptibility in the mouse.