Arrhythmias are abnormalities of the heart rate or rhythm caused by disorders of impulse generation or conduction.

Disorders of Impulse Generation: Latent Pacemakers and Triggered Automaticity

All parts of the cardiac conduction system demonstrate a spontaneous phase 4 depolarization (automaticity), and are therefore potential or latent pacemakers. Because sinoatrial node (SAN) pacemaking is of the highest frequency (70–80 beats/min), it causes overdrive suppression of pacemaking by the atrioventricular node (AVN) (50–60 beats/min) or Purkinje fibres (30–40 beats/min). However, ischaemia, hypokalaemia, fibre stretch or local catecholamine release may increase automaticity in latent pacemakers, which can then ‘escape’ from SAN dominance to cause arrhythmias.

Triggered automaticity is caused by afterdepolarizations. These are oscillations in the membrane potential that occur during or after repolarization. Oscillations large enough to reach threshold initiate premature action potentials and thus heart beats (Figure 48a). This may occur repeatedly, initiating a sustained arrhythmia either directly or by triggering re-entry (see below). Afterdepolarization magnitude is influenced by changes in heart rate, catecholamines and parasympathetic withdrawal.

Early afterdepolarizations (EADs) occur during the terminal plateau or repolarization phases of the action potential. They develop more readily in Purkinje fibres than in ventricular or atrial myocytes. EADs can be induced by agents that prolong action potential duration and increase the inward current. For example, drugs such as sotalol which block K⁺ currents can cause EADs and triggered activity by delaying repolarization, especially when the heart rate is slow. The abnormal rhythms induced by such drugs resemble torsade de pointes, a type of congenital arrhythmia.

Delayed afterdepolarizations (DADs) occur after repolarization is complete, and are caused by excessive increases in cellular [Ca²⁺]. DADs can be caused by catecholamines, which increase Ca²⁺ influx through the L-type Ca²⁺ channel, and by digitalis glycosides, which increase [Ca²⁺]_i (see Chapter 47). They can also occur in heart failure, in which myocyte Ca²⁺ regulation is impaired. The oscillation of membrane potential following the increase in [Ca²⁺]_i is caused by a transient inward current involving Na⁺ influx, and the occurrence and magnitude of DADs and the likelihood that they will cause arrhythmias is increased by conditions that enhance this current. These include increased Ca²⁺ release from the sarcoplasmic reticulum and longer action potentials, which cause larger increases in [Ca²⁺]_i. Therefore, drugs prolonging action potential duration may trigger DADs, whereas drugs shortening the action potential have the opposite effect. The magnitude of the transient inward current is also influenced by the resting membrane potential, and is maximal when this is approximately −60 mV.

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