4.2: Mechanisms of Arrhythmia

Structural abnormalities or electric changes in the cardiomyocytes can impede impulse formation or change cardiac propagation, therefore facilitating arrhythmias. Arrhythmogenic mechanisms can arise in single cells (automaticity, triggered activity), but other mechanisms require multiple cells for arrhythmica induction (re-entry). We briefly discuss the pathophysiological mechanisms of the main causes of arrhythmia. [5]

Abnormal Impulse Formation

Abnormal Automaticity

The mechanism of abnormal automaticity is similar to the normal automaticity of sinus node cells. Abnormal automaticity can be caused by changes in the cell ion channel characteristics due to drugs (digoxine) or changes in the electrotonic environment (myocardial infarction). Abnormal automaticity can result from an increase of normal automaticity in non-sinus node cells or a truly abnormal automaticity in cells that don't exhibit a phase 4 diastolic depolarization. An important phenomenon in (both normal and abnormal) automaticity is overdrive suppression. In overdrive suppression the automaticity of cells is reduced after a period of high frequency excitation. The cellular mechanism responsible for this effect is an increased activity of the Na⁺, K⁺ pump (I_{Na, K}) which results in an increased efflux of Na⁺, thereby inducing a hyperpolarization.[2]

Triggered Activity

Triggered activity is depolarization of a cell triggered by a preceding activation. Due to early or delayed afterdepolarizations the membrane potential depolarizes and, when reaching a threshold potential, activates the cell. These afterdepolarizations are depolarizations of the membrane potential initiated by the preceding action potential. Depending on the phase of the action potential in which they arise, they are defined as early or late afterdepolarizations (Figure 4.2.1).

Figure 4.2.1: The different mechanisms of arrhythmia.

• A disturbance of the balance in influx and efflux of ions during the plateau phase (phase 2 or 3) of the action potential is responsible for the early afterdepolarizations. Multiple ion currents can be involved in the formation of early after depolarizations depending on the triggering mechanism. Early afterdepolarizations can develop in cells with an increased duration of the repolarization phase of the action potential, as the plateau phase is prolonged. The prolonged repolarization might reactivate the Ca²⁺ channels that have recovered from activation at the beginning of the repolarization. Otherwise disparity in action potential duration of surrounding myocytes can destabilize the plateau phase through adjacent depolarizing currents.
• Delayed afterdepolarizations occur after the cell has recovered after completion of repolarization. In delayed afterdepolarization an abnormal Ca²⁺ handling of the cell is responsible for the afterdepolarizations due to release of Ca²⁺ from the storage of Ca²⁺ in the sarcoplasmatic reticulum. The accumulation of Ca²⁺ increases membrane potential and depolarizes the cell until it reaches a certain threshold, thereby creating an action potential. A high heart rate can result in the accumulation of intracellular Ca²⁺ and induce delayed afterdepolarizations.

Disorders of Impulse Conduction

Conduction block

Conduction block or conduction delay is a frequent cause of bradyarrhythmias, especially if the conduction block is located in the cardiac conduction system. However tachyarrhythmias can also result from conduction block when this block produces a re-entrant circuit (see below). Conduction block can develop in different (pathophysiological) conditions or can be iatrogenic (medication, surgery).

Re-entry

Re-entry or circus movement is a multicellular mechanism of arrhythmia. Important criteria for the development of re-entry are a circular pathway with an area in this circle of unidirectional block and a trigger to induce the re-entry movement. Re-entry can arise when an impulse enters the circuit, follows the circular pathway and is conducted through an unidirectional (slow conducting) pathway. Whilst the signal is in this pathway the surrounding myocardium repolarizes. If the surrounding myocardium has recovered from the refractory state, the impulse that exits the area of unidirectional block can reactivate this recovered myocardium. This process can repeat itself and thus form the basis of a re-entry tachycardia. Slow conduction and/or a short refractory period facilitate re-entry. The reason of unidirectional block can be anatomical (atrial flutter, AVNRT, AVRT) or functional (myocardial ischemia) or a combination of both.[6, 7]