16
Action Potential Features and Propagation: Mechanisms of Arrhythmias, Antiarrhythmic Drugs

I. Action potential (see Figures 16.1, 16.2)

II. Action potential propagation and mechanisms of arrhythmias

Two features characterize the propagation of the action potential: (1) how fast it propagates, i.e., conduction velocity; and (2) how fast it recovers and accepts new impulses, i.e., refractory period. Some tissues, like the slow AV nodal pathway, have a slow conduction yet a fast refractory period (in comparison to the fast AV nodal pathway). Other tissues, like the accessory pathway, have a fast conduction but a slow refractory period (in comparison to the AV node).

An arrhythmia may result from the following mechanisms:

Reentry (the most common mechanism, shown in Figures 16.3–16.6).
Increased automaticity. In this case, atrial or ventricular myocardial cells develop abnormal pacing capacity with spontaneous diastolic depolarization (e.g., accelerated idioventricular rhythm). Alternatively, after a pause, latent pacemaker cells may start firing in phase 4 (e.g., ventricular escape rhythm). Like sinus tachycardia, which is an automatic rhythm, an automatic arrhythmia generally displays a warm-up phenomenon at onset and warm-down phenomenon at offset.
Triggered activity secondary to afterdepolarizations. Afterdepolarizations are depolarizing oscillations in membrane potential that occur during the late part of phase 3 repolarization (early afterdepolarization, EAD) or during phase 4 (delayed afterdepolarization, DAD). If the afterdepolarization reaches a threshold potential, arrhythmia may be initiated (Figure 16.7). Afterdepolarization, whether EAD or DAD, is related to excessive intracellular accumulation of calcium. EADs are mainly seen during a very prolonged repolarization that allows spontaneous calcium release from the sarcoplasmic reticulum (e.g., after a pause or bradycardia). DADs, on the other hand, are promoted by a fast heart rate rather than a pause; the fast heart rate impedes reuptake of calcium into the sarcoplasmic reticulum, which increases intracytosolic calcium accumulation and thus the amplitude of DADs.

EAD-triggered activity may be due to a congenital or acquired long QT syndrome, electrolyte disturbances, or antiarrhythmic drugs. Automaticity and DAD-triggered activity are generally due to ischemia, catecholamine excess, hypoxia, acid–base disorders, or calcium overload from digoxin toxicity. Automaticity may also be due to cavity stretch.

A premature ventricular or atrial complex results from the same three mechanisms. In patients with heart disease, a change in sinus rate may create a ventricular reentry around the abnormal myocardial tissue, which could be isolated (PVC) or could become sustained into VT. PVC may also result from triggered activity arising from the abnormal tissue, which is a tissue prone to spontaneous depolarization, or fractionated late diastolic potential (a form of automaticity). Overall, the morphologies of the PVC and VT are frequently similar. Idiopathic PVCs arising from the RVOT are generally due to triggered activity.

All arrhythmias can exhibit a warm-up phenomenon, wherein the rate quickly accelerates upon initiation, but this is most characteristic of automatic tachycardias (such as automatic atrial tachycardia).

Induction of arrhythmias in the EP lab- Reentry can be initiated by pacing or by premature impulses. Reentry can be terminated by overdrive pacing or by premature impulses that enter the reentrant circuit and get blocked inside it, breaking it.

Conversely, pacing and premature impulses are not effective in initiating or terminating automatic tachycardias, which are thus difficult to induce in the EP lab. In fact, in the EP lab, automatic tachycardia is defined as a tachycardia that cannot be initiated or terminated with programmed electrical stimulation. Also, as opposed to reentry, automatic tachycardias do not respond well to DC cardioversion, as the automatic focus keeps firing independently of the surrounding electrical stimuli.

Schematic illustration of action potential of atrial and ventricular myocardium. — **Figure 16.1** Action potential of atrial and ventricular myocardium. Phase 0 corresponds to myocardial depolarization and QRS on ECG, phases 1 and 2 (plateau) correspond to the ST segment, phase 3 corresponds to the T wave, and phase 4 corresponds to the TP segment. Phases 1–3 correspond to repolarization, during which the cells are refractory to a new depolarization (refractory period). All myocardial cells reach the same phase 2 plateau level around the same time, and thus the ST segment is normally a flat isoelectric segment without intramyocardial gradient. Conversely, the T wave is like the bell curve of the repolarization of all myocardial cells, some of which repolarize early, and some late. The width of T and the length of QT indicate, in a way, how heterogeneous and dispersed the repolarization is, and thus the risk of arrhythmia. The normal U wave is a diastolic wave related to the mechanical stretch of the myocardium in phase 4 (diastole). The abnormal U wave could be part of phase 4 (delayed afterdepolarization, DAD), or part of phase 3 in patients with prolonged repolarization (early afterdepolarization [EAD] seen in patients with prolonged QT). In the latter patients, the U wave is actually a T2 repolarization wave; their QT is a QTU interval, and the distinction between T and U may not be very relevant in these patients.

The depolarization of one cell causes the sodium channels of adjacent cells to open and depolarize. There are two properties of electrical propagation: **(1) conduction velocity**, which depends on phase 0; **(2) refractory period**, which depends on the duration of phases 2–3. A reduction in the steepness of phase 0 (dashed phase 0, class I AAD) leads to slower velocity and wide QRS, while a prolonged phase 3 (dashed phase 3, class III AAD) leads to a prolonged QT interval.

Phase 1 uses I_Kto (transient outward K channel), phases 2 and 3 use outward I_Kr and I_Ks, and phase 4 depends on inward IK1 and on Na/K pump, which pumps 3 Na out and 2 K in, creating the negative baseline intracellular potential (the cell potential is close to the equilibrium potential of K).

**The action potential duration is increased at lower heart rates, and is reduced with tachycardia or β-adrenergic stimulation.** It is mainly the duration of phase 3 that is affected with changes in heart rate.

↓ indicates the entry of the ion inside the cell; ↑ indicates the exit of the ion.

Schematic illustration of action potential of the SA and AV nodes is characterized by a spontaneous depolarization in phase 4. — **Figure 16.2** Action potential of the SA and AV nodes is characterized by a spontaneous depolarization in phase 4. In addition, phase 0 is characterized by calcium rather than sodium entry, explaining the effect of calcium channel blockers on slowing the SA and AV node. Phase 0 is also slower than phase 0 of the atrial and ventricular cells, thus explaining the slower conduction through the AV node. Phase 4 depends on the funny K and Na channel (If). Spontaneous phase 4 depolarization may be seen in ischemic atrial or ventricular cells (increased automaticity).

Triggered activity can be spontaneous like automaticity, resulting from leakage of positive ions into the myocardial cell, but can also be induced with a premature beat or with a pause, particularly a pause introduced after fast pacing. Similarly to reentry, it may get entrained with pacing or terminated. Thus, during EP study, triggered activity resembles reentry. Since it depends on calcium channels, triggered activity may respond to calcium channel blockers (Table 16.1).

Schematic illustration of reentry as a mechanism of tachyarrhythmia. — **Figure 16.3** Illustration of reentry as a mechanism of tachyarrhythmia. In order to have reentry, adjacent myocardial areas (A and B) need to have **different refractory periods and different conduction velocities, separated by an anatomical or functional barrier. The pathway with the shorter refractory period needs to have a slower conduction.** The larger the difference in refractory period between A and B, the easier it is to initiate an arrhythmia; this difference between refractory periods is called the **tachycardia zone**. The slower the conduction velocity in A, the more likely it is to sustain the arrhythmia (slow conduction leads to a large ***excitable gap***, Figure 16.4). When the rhythm is regular, the electrical activity spreads through both areas simultaneously (*top*). After a **premature beat**, region B is still in its long refractory period, but region A has recovered (*lower left*). The electrical activity spreads through region A, then meets the tail end of region B; at that time, if region B has not recovered from its refractory period, arrhythmia does not occur (i). Since A conducts slowly, region B may well recover from its refractory period, allowing conduction to spread retrogradely through region B (ii). Eventually, this retrograde impulse reaches A faster than the electrical activity originating from the sinus node reaches A. Since A has a short refractory period, the impulse may propagate through A and stimulate the whole cardiac chamber again. Thus, this circle keeps repeating itself, stimulating the myocardial tissue at a rate faster than normal: this is the reentrant tachyarrhythmia.

These areas of slow conduction and different refractory period are seen around a scar (prior infarct, fibrosis, cardiomyopathy), an ischemic area, or a functionally slow area (crista terminalis for atrial flutter, slow pathway of AVNRT) or fast area (accessory pathway of AVRT). Scarred myocardium is an anatomic barrier for reentry. **The peri-scar myocardium has a slow conduction, but shorter action potential and shorter repolarization than the surrounding tissue.** An area is functionally slow when fibers in that area are organized transversally rather than longitudinally; electrical activity spreads more slowly transversally than longitudinally through gap junctions.

PVC or ventricular pacing may have three effects on a reentry that involves the ventricle (VT, AVRT) (Figure 16.5):

The PVC or ventricular pacing may conduct into the reentry and block it.
The PVC or ventricular pacing may enter the reentrant circuit and become part of it. Pacing at a rate faster than the tachycardia cycle length may actually entrain the tachycardia, if the refractory period is short enough and the excitable gap large enough to prevent pacing from being blocked in the reentry circuit. This is evident on the ECG by the fact that the interval between the last paced beat (or PVC) and the next QRS, i.e., post-pacing interval, is equal to the R–R interval of the tachycardia (if pacing is close enough to the reentrant zone, which is usually the case if one can engage the reentry). This is called resetting of the tachycardia. Since fast pacing may shorten the cycle length of the tachycardia and accelerate it, antitachycardia pacing may be risky.
In the case of VT microreentry, the ectopic or pacing focus may be far from the reentry, so that it conducts to the ventricles and prevents most or all of the ventricular myocardium from being activated through the reentry. The reentry, however, keeps looping independently, unaffected by the faraway pacing, with a post-pacing interval longer than the tachycardia cycle length. This does not usually happen with AVRT, where the reentry involves a large part of the ventricular myocardium; pacing either conducts through the AVRT or breaks it.

AVNRT and atrial tachycardia may break with PVC or ventricular pacing if it conducts retrogradely and enters the reentrant circuit. This is unlikely to happen, as the loops of AVNRT and atrial tachycardia are far from the ventricle. Usually, their cycle will not be affected, they keep looping independently of the QRS at their own pre-existing rate and atrial activity often becomes dissociated from ventricular activity (Figure 16.8).

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Tags: Practical Cardiovascular Medicine

Nov 27, 2022 | Posted by admin in CARDIOLOGY | Comments Off

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Action Potential Features and Propagation

16
Action Potential Features and Propagation: Mechanisms of Arrhythmias, Antiarrhythmic Drugs

I. Action potential (see Figures 16.1, 16.2)

II. Action potential propagation and mechanisms of arrhythmias

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