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(Circulation Research. 2000;87:725.)
© 2000 American Heart Association, Inc.

Editorial

When Does Spontaneous Sarcoplasmic Reticulum CA²⁺ Release Cause a Triggered Arrythmia? Cellular Versus Tissue Requirements

Steven R. Houser

From the Cardiovascular Research Group, Temple University, School of Medicine, Philadelphia, Pa.

Correspondence to Steven R. Houser, PhD, Cardiovascular Research Group, Temple University, School of Medicine, 3400 N Broad St, Philadelphia, PA 19034. E-mail srhouser@unix.temple.edu

Key Words: triggered arrhythmias • nonreentrant arrhythmias • Ca²⁺ overload • Ca²⁺-activated currents • Na⁺-Ca²⁺ exchange

	Introduction

 
Ventricular arrhythmias are a major cause of sudden premature death in patients with ischemic heart disease, hypertrophy, and congestive heart failure. The processes that initiate these arrhythmias include reentry, abnormal automaticity, and triggered activity.^{1 2} In the past three decades, there has been substantial investigation into each of these processes.^{3 4} This discussion will focus on triggered activity caused by delayed afterdepolarizations (DADs).

Triggered activity has been widely studied for more than 20 years in whole hearts, isolated myocytes, and muscle and in Purkinje fiber preparations.^{5 6} Two general types of triggered afterdepolarizations have been observed and characterized. Early afterdepolarizations occur during the plateau phase of long-duration action potentials (APs). These secondary depolarizations involve either reactivation of the L-type Ca²⁺ channel or Na⁺ channel.^{6 7} DADs occur after repolarization of the AP to the resting potential and are caused by spontaneous release of Ca²⁺ from the sarcoplasmic reticulum (SR).^{6 8 9 10 11 12} The resulting elevation of cytosolic free Ca²⁺ activates inward current(s) that causes diastolic depolarization. When DADs are of a sufficient magnitude, an AP is induced. In the intact heart, these APs can propagate throughout the myocardium to cause extra heartbeats. In addition, if they find the ventricle in a partially refractory state or with conduction abnormalities, these APs can lead to tachyarrhythmias and fibrillation.

It is well established that DADs result from spontaneous Ca²⁺ release from a Ca²⁺-overloaded SR.^{9 10 11} Many early studies of DADs used cardiac glycosides to increase cellular and SR Ca²⁺ and induce Ca²⁺ overload. It is now clear that many other . . . [Full Text of this Article]

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