Triggered activity occurs when after-depolarizations in-duced by a preceding action potential raise the resting membrane potential above the threshold value, leading to an additional action potential. After-depolarizations may be categorized as early, occurring during phase III of the action potential before achieving full repolarization, or delayed, occurring after full repolarization of the membrane. After-depolarizations may stimulate an iso-lated extrapropagated impulse or lead to sustained repet-itive activity. The crucial difference between triggered ac-tivity and abnormal automaticity is that triggered activity depends on a preceding action potential and cannot be self-induced. After-depolarizations or triggered activity are often associated with excessive increases in intracel-lular [Ca ]. The potential for development of triggered activity is accentuated in the presence of an increase in extracellular [Ca ] that would increase the amount of ionized calcium entering the cell during depolarization. Furthermore, conditions or pharmacological interven-tions favoring prolongation of the plateau (phase 3) of the action potential and prolongation of the QT interval of the electrocardiogram would increase intracellular [Ca++ ] and the potential for proarrhythmia.
Early after-depolarizations are purported to be the mechanism giving rise to torsades de pointes. Conditions or drugs known to prolong the action potential, espe-cially by interventions that decrease the outward potas-sium currents, facilitate development of torsades de pointes tachyarrhythmias. Early after-depolarizations may develop in association with hypokalemia, hypoxia, acidosis, and a wide range of pharmacological agents that interfere with outward currents or enhance inward currents. Antiarrhythmic agents, in particular sotalol, quinidine, and dofetilide, may give rise to after-depolar-izations and torsades de pointes tachyarrhythmia in persons with underlying cardiac abnormalities or alter-ations in plasma electrolytes. Conditions leading to bradycardia also may facilitate development of torsades de pointes tachyarrhythmia.
Early after-depolarizations and the associated ven-tricular arrhythmia can be prevented or suppressed by the appropriate adjustment of plasma potassium and/or magnesium concentrations. Lidocaine or procainamide may be effective for termination of the arrhythmia.
Delayed after-depolarizations (Figure 16.4) may oc-cur in the presence of a rapid heart rate, digitalis glyco-sides, hypokalemia, hypercalcemia and catecholamines. Each of these influences ultimately leads to an increase in intracellular ionized calcium that is known to activate an inward ionic current. The inward ionic current acti-vates a nonselective channel that normally is involved with the transport of sodium but that under pathophys-iological conditions may permit the movement of sodium or potassium ions. Upon reaching threshold, the calcium-induced oscillatory potentials lead to the pro-duction of a sustained ventricular arrhythmia. Delayed after-depolarizations, in contrast to early after-depolar-izations, are more likely to produce triggered tachy-arrhythmias during periods of short pacing cycle lengths (rapid heart rates). Exercise-induced ventricular tachy-cardia in persons without overt cardiac disease exem-plifies such a situation. The electrophysiological abnor-mality is catecholamine dependent and calcium sensitive. The arrhythmia may respond to L-type cal-cium channel antagonists or inhibitors of the cardiac β-adrenoceptor. Each of these approaches would serve to reduce the tissue calcium concentration.
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