Anger, emotion, and arrhythmias: from brain to heart

Abstract

Strong emotion and mental stress are now recognized as playing a significant role in severe and fatal ventricular arrhythmias. The mechanisms, although incompletely understood, include central processing at the cortical and brain stem level, the autonomic nerves and the electrophysiology of the myocardium. Each of these is usually studied separately by investigators from different disciplines. However, many are regulatory processes which incorporate interactive feedforward and feedback mechanisms. In this review we consider the whole as an integrated interactive brain-heart system.

Keywords: anger; brain–heart system; emotion; mental stress.

Figure 1

The theme of this review is to consider the brain and heart as an interactive unit and its role in the generation of ventricular arrhythmias. Key components are (1) the electrophysiological changes occurring in the myocardium as a result of autonomic nerve stimulation; (2) the modulatory role of the sympathetic and parasympathetic nerves which tend to oppose and balance each other (3) central neural processing of emotional input and afferent input from the heart and circulation. Sympathetic nerve stimulation acting through β-adrenergic receptors influences a number of ion channels and transporters in cardiac myocytes. These effects include an increase in inward calcium current ICa and decrease in outward potassium current I_k, thereby tending to lengthen and shorten action potential duration (and refractoriness) respectively. Sympathetic stimulation favors the formation of both early after depolarizations (EAD) and delayed after depolarizations (DAD). These effects may be proarrhythmic as a result of triggered activity and/or modulation of refractoriness.

Figure 2

The two components of the autonomic nervous system, the sympathetic nerves and parasympathetic (vagus) nerves tend to act in a reciprocal manner such that, for example, an increase in sympathetic activity is accompanied by a decrease (or lesser increase) in parasympathetic activity. Evidence suggests that the right cerebral hemisphere is predominantly concerned with negative emotion and sympathetic activity, whereas the left hemisphere is predominantly concerned with positive emotion and parasympathetic activity. Autonomic nerve traffic from the brain to the heart is mainly ipsilateral between the brainstem and heart. There is also some degree of lateralization of the distribution of the right and left autonomic nerves on the heart. These considerations form the basis for the laterality hypothesis whereby central neural processes may be represented asymmetrically on the heart and thereby induce inhomogeneous repolarization and be proarrhythmic.

Figure 3

Schematic representation of β-adrenergic signaling in cardiomyocytes. Sympathetic stimulation and the consequent neurotransmitter release initiates the β-adrenergic signaling cascade in cardiomyocytes. Agonist binding to the β-adrenergic receptor (β-ADR) activates, via G_s, the plasma membrane bound adenylate cyclase (AC), which catalyzes the conversion of ATP to cAMP. cAMP activates I_f and PKA. PKA modulates, via phosphorylation, a number of cellular substrates, including ion channels, transporters, exchangers, intracellular Ca²⁺-handling proteins, and the contractile machinery.

Figure 4

Genetic predisposition to emotion and stress induced arrhythmias.