Cardiac Mechano-Electric Coupling: Acute Effects of Mechanical Stimulation on Heart Rate and Rhythm

Abstract

The heart is vital for biological function in almost all chordates, including human. It beats continually throughout our life, supplying the body with oxygen and nutrients while removing waste products. If it stops - so does life. The heartbeat involves precise coordination of the activity of billions of individual cells, as well as their swift and well-coordinated adaption to changes in physiological demand. Much of the vital control of cardiac function occurs at the level of individual cardiac muscle cells, including acute beat-by-beat feedback from the local mechanical environment to electrical activity (as opposed to longer-term changes in gene expression, and functional or structural remodelling). This process is known as Mechano-Electric Coupling (MEC). In the current review, we: present evidence for, and implications of, MEC in health and disease in human; summarise our understanding of MEC effects gained from whole animal, organ, tissue, and cell studies; identify potential molecular mediators of MEC responses; and demonstrate the power of computational modelling in developing a more comprehensive understanding of 'what makes the heart tick'.

Sinoatrial Node Structure, Mechanics, Electrophysiology and the Chronotropic Response to Stretch in Rabbit and Mouse

“…The SAN also responds to altered hemodynamic load through the Bainbridge response: an increase in BR upon right atrial distention, which may help in matching cardiac output to venous return (Bainbridge, 1915). This response was initially thought to be neurally mediated; however, mechanically induced changes in BR have since been demonstrated in isolated heart, atria, SAN, and single SAN cells, indicating the involvement of mechano-sensitive mechanisms (Quinn and Kohl, 2020) intrinsic to pacemaker cells (Quinn and Kohl, 2012). Here, we investigate how structural and mechanical properties of the SAN relate to amplitude and directionality of stretch-induced changes in BR, including a comparison between rabbit and mouse as important species-specific differences may exist (Cooper and Kohl, 2005).…”

Mechanical stimulation of endocardial Purkinje fibres can trigger ventricular arrhythmias

“…Variation in the type of mechanically activated arrhythmia has been previously reported (e.g. Franz et al, 1992;Kohl et al, 2011;Quinn et al, 2017;Quinn & Kohl, 2020). In the rat LV, ectopics with a negative R-wave may originate from either the myocardium or the distal Purkinje network distant from origins affiliated with the normal sinus rhythm (e.g.…”

“…The inter-dependence of mechanical and electrical activity is demonstrated by the processes of excitation-contraction coupling (Bers, 2002) and mechano-electric feedback/coupling (Orini et al, 2017;Quinn & Kohl, 2020). A manifestation of these interactions are mechanically-induced arrhythmias which occur in several clinical settings such as atrial fibrillation, commotio cordis, hypertrophy and heart failure e.g.…”

“…(Quinn et al, 2017) showed that in isolated rabbit hearts, focal mechanical stimulation of the epicardial surface could trigger arrhythmias arising from the site of mechanical stimulation. Mechanically-induced arrhythmias are typically explained in terms of the activation of stretch-activated, non-specific cationic ion channels within the myocardium, though the identity of these in the ventricular myocardium is uncertain (White, 2006;Syeda et al, 2015;Quinn & Kohl, 2020).…”

“…PFs are recognised as an important factor in clinical arrhythmias e.g. (Haissaguerre et al, 2016) as are mechanically-induced arrhythmias (Orini et al, 2017;Quinn & Kohl, 2020).…”