Early afterdepolarizations

A cell may produce early afterdepolarizations that are depolarization during incomplete repolarization. This is possible if the action potential is considerably prolonged. This is the typical mechanism for elicitation of Torsade de Pointes arrhythmia, a typical complication of class III antiarrhythmics and many other drugs. 

Verduyn AC, Vos MA, van der Zande J et at. (1997) Further observations to elucidate the role of interventricular dispersion of repolarization and early afterdepolarizations in the genesis of acquired Torsade de Points arrhythmias. J Am Coll Cardiol 30 1575-1584... 

Vos MA, Verduyn SC, Gorgels APM et al. (1995) Reproducible induction of early afterdepolarizations and torsade de pointes arrhythmias by d-sotalol and pacing in... 

Figure 5 Reduction of Irt prolongs action potential duration. Here, the prolongation effects of 25%, 50%, and 75% reduction of h r on APD are shown in a virtual cell model after 1000 paced beats at a cycle length (CL) = 1000 ms. A 75% current reduction results in the development of arrhythmogenic early afterdepolarizations (EADs). [Adapted from (38).]...

Calcium overload is manifested as an early afterdepolarization of the cardiac action potential, which may result in premature depolarization of Purkinje fibers and the appearance of ventricular arrhythmias. With substantially increased calcium load, this may lead to ventricular tachyarrhythmias and death. 

Cardiac glycosides increase the influx of calcium, and decrease the outflow of potassium. Because there is little sequestration of calcium in cardiac cells, intracellular calcium may increase to toxic levels, particularly with high doses of the drug, and may exchange for sodium, via the sodium-calcium exchanger. This results in an overload of intracellular sodium and calcium, which, because of the decreased outflow of potassium, is not counterbalanced. Thus, calcium overload is manifested as an early afterdepolarization of the cardiac action potential, which may result in premature depolarization of Purkinje fibers and the appearance of ventricular arrhythmias, which may result in ventricular tachyarrhythmias and death. 

ABBREVIATIONS AV, atrioventricular DAD, delayed afterdepolarization DC, direct current HAD, early afterdepolarization WPW, Wolff-Parkinson-White supraventricular tachycardia IV, intra-X venous T, increase -I, decrease , unclear. 

Bailie DS, Inoue H, Kaseda S, Ben-David J, Zipes DP (1988) Magnesium suppression of early afterdepolarizations and ventricular tachyarrhythmias induced by cesium in dogs. Circulation 77 1395-1402... 

January CT, Riddle JM (1989) Early afterdepolarizations mechanism of induction and block. 

Swift F, Tovsrud N, Enger UH, SJaastad I, Sejersted OM (2007) The Na /K -ATPase a2-isoform regulate cardiac contractility in rat cardiomyocytes. Cardiovasc Res 75 109-117 Szabo B, Sweidan R, Rajagopalan CV, Lazzara R (1994) Role of Na Ca exchange current in Cs -induced early afterdepolarization in Purkinje fibers. J Cardiovasc Electrophysiol 5 933-944... 

Szabo B, Kovacs T, Lazzara R (1995) Role of calcium loading in early afterdepolarization generated by Cs" in canine and guinea pig Purkinje fibers. J Cardiovasc Electrophysiol 6 796-812... 

Lu HR, Marien R, Saels A, De Clerck F (2000). Are there sex-specific differences in ventricular repolarization or in drug-induced early afterdepolarizations in isolated rahhit Purkinje fibers J Cardiovasc Pharmacol 36 132-139. 

Lu HR, Vlaminckx E, Van Ammel K, De Clerck F (2002). Drug-induced long QT in isolated rabbit Purkinje fibers importance of action potential duration, triangulation and early afterdepolarizations. Eur J Pharmacol 452 183-192. 

Administration of magnesium sulfate is currently recommended as immediate first-line treatment for torsades (Zipes et al. 2006). While the mechanism of action is uncertain, magnesium may reduce the amplitude of early after-depolarizations by inhibiting the late influx of calcium ions via L-type calcium channels that are associated with delayed ventricular repolarization. Consequently, early afterdepolarizations are less likely to reach threshold potential and provoke or sustain torsades (Kaye and O Sullivan 2002). 

Studemk CR, Zhou Z, January C (2001) Differences in action potential and early afterdepolarization properties in LQT2 and LQT3 models of long QT syndrome. Br J Pharmacol... 

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