Pre-existing heterogeneities present in cardiac tissue are essential for maintaining the normal electrical and mechanical functions of the heart. Exacerbation of such heterogeneities or the emergence of dynamic factors can produce repolarization alternans, which are beat-to-beat alternations in the action potential time course. Traditionally, this was explained by restitution, but additional factors, such as cardiac memory, calcium handling dynamics, refractory period restitution, and mechano-electric feedback, are increasingly recognized as the underlying causes. The aim of this article is to review the mechanisms that generate cardiac repolarization alternans and convert spatially concordant alternans to the more arrhythmogenic spatially discordant alternans. This is followed by a discussion on how alternans generate arrhythmias in a number of clinical scenarios, and concluded by an outline of future therapeutic targets for anti-arrhythmic therapy.

Action potential duration (APD) and conduction velocity restitution explain the dependence of these parameters on the previous diastolic interval (DI). It is considered to be an adaptive mechanism for preserving diastole at fast heart rates. Hypokalaemia is known to induce ventricular arrhythmias that could be prevented by heptanol, the gap junction uncoupler, mediated through increases in ventricular refractory period (VERP) without alterations in APDs. The present study investigated alternans and restitution properties during normokalaemia, hypokalaemia alone or hypokalaemia with heptanol (0.1 mM) in Langendorff-perfused mouse hearts using a dynamic pacing protocol. APD90 alternans were elicited in the epicardium and endocardium during normokalaemia. Hypokalaemia increased the amplitudes of epicardial APD90 alternans when basic cycle lengths (BCLs) were ≤65 msec, which was associated with increases in maximum APD90 restitution gradients, critical DIs and APD90 heterogeneity. Heptanol (0.1 mM) did not exacerbate or reduce the APD90 alternans or alter these restitution parameters further. By contrast, endocardial APD90 alternans did not show increases in amplitudes during hypokalaemia at short BCLs studied, and restitution parameters were also unchanged. This was true whether in the presence or absence of 0.1 mM heptanol. The study demonstrates that anti-arrhythmic effects of heptanol exerted during hypokalaemia occurred despite exacerbation of APD90 alternans. This would suggest that even in the presence of arrhythmogenic APD90 alternans, arrhythmias could still be prevented by influencing VERP alone. Restitution data obtained here by dynamic pacing were compared to previous data from S1S2 pacing.

The aim of this article is to provide an overview of current debate on the monophasic action potential (MAP) recording technique, specifically whether the depolarizing or the reference electrode is responsible for recording the MAP waveform. A literature search was made using key words including monophasic action potential, MAP, electrophysiological basis, recording electrode, depolarizing electrode, contact electrode, indifferent electrode, and reference electrode. References from articles were screened for additional relevant papers. Articles published by the different experimental groups claim that depolarizing electrode, but not reference electrode, records MAPs from the myocardium. This can be more accurately described when considering biophysical theory, which states that MAP is a bipolar signal with contributions from not only the depolarizing electrode but also remote activation at the reference electrode. It is not meaningful to claim that one is the recording electrode because potential differences must be measured between two points in space. Nevertheless, the MAP technique is useful for assessing the local electrical activity of the myocardium in contact with the depolarizing electrode. It is important to have the recording electrode in close proximity with the reference electrode to minimize contamination from far-field signals.

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The present study examined the ventricular arrhythmic and electrophysiological properties during hyperkalemia (6.3 mM [K+] vs. 4 mM in normokalemia) and anti-arrhythmic effects of hypercalcemia (2.2 mM [Ca2+]) in Langendorff-perfused mouse hearts. Monophasic action potential recordings were obtained from the left ventricle during right ventricular pacing. Hyperkalemia increased the proportion of hearts showing provoked ventricular tachycardia (VT) from 0 to 6 of 7 hearts during programmed electrical stimulation (Fisher's exact test, P<0.05). It shortened the epicardial action potential durations (APDx) at 90, 70, 50 and 30% repolarization and ventricular effective refractory periods (VERPs) (analysis of variance, P<0.05) without altering activation latencies. Endocardial APDx and VERPs were unaltered. Consequently, ∆APDx (endocardial APDx-epicardial APDx) was increased, VERP/latency ratio was decreased and critical intervals for reexcitation (APD90-VERP) were unchanged. Hypercalcemia treatment exerted anti-arrhythmic effects during hyperkalemia, reducing the proportion of hearts showing VT to 1 of 7 hearts. It increased epicardial VERPs without further altering the remaining parameters, returning VERP/latency ratio to normokalemic values and also decreased the critical intervals. In conclusion, hyperkalemia exerted pro-arrhythmic effects by shortening APDs and VERPs. Hypercalcemia exerted anti-arrhythmic effects by reversing VERP changes, which scaled the VERP/latency ratio and critical intervals.