Delayed afterdepolarization-mediated triggered activity associated with slow calcium sequestration near the endocardium

Calcium-Mediated Triggered Activity. Introduction: Previously, we have shown that cells near the endocardium are more prone to elevated diastolic intracellular calcium levels than cells near the epicardium. The arrhythmogenic consequence of such regional differences in calcium handling is not clear. Methods and Results: Using optical mapping techniques, calcium transients and action potentials were recorded simultaneously from ventricular sites across the transmural wall of the arterially perfused canine left ventricular wedge preparation during control conditions, and under conditions of increased calcium entry (I-K blockade and beta-adrenergic stimulation). Under conditions of enhanced calcium entry, the decay of the calcium transient and diastolic calcium levels during rapid pacing were slower (38%, P < 0.01) and higher (215%, P < 0.02), respectively, near (within similar to 3 mm) the endocardium compared to the epicardium (n = 9). Immediately after termination of rapid pacing under conditions of increased calcium entry, ectopic activity and simultaneous delayed afterdepolarizations and spontaneous calcium release events were observed. Over all experiments, ectopic activity occurred more frequently closer to the endocardium compared to the epicardium. Conclusions: Under conditions of enhanced calcium entry, myocytes closer to the endocardium exhibit a higher level of diastolic calcium and greater ectopic activity compared to the epicardium. We show for the first time simultaneous delayed afterdepolarization and spontaneous calcium release events from myocytes in a normally coupled multicellular preparation. These data combined suggest that myocytes near the endocardium are more susceptible to calcium-mediated triggered activity.