Electrical and Calcium Transient Alternans in Cell Pairs and Intact Atrium

Abstract

Cardiac arrhythmias, such as atrial fibrillation (AF), require an arrhythmogenic focus (ectopic activity) and transient or permanent tissue inhomogeneity (conduction heterogeneity). Electrical and calcium alternans in atrial tissue represent a risk factor for the occurrence of AF. The aims of our study were to determine characteristics of the development of Ca transient (CaT) alternans in coupled pairs of atrial myocytes and the relationship between cellular atrial alternans and occurrence of AF episodes in the perfused intact heart. Atrial cell pairs isolated from rabbit hearts were field stimulated at increasing rates until CaT alternans occurred. The CaT alternans usually initiated in one cell first. Alternans in the second cell rarely occurred simultaneously (3/11 pairs), but rather started at higher frequencies (5/11 pairs), or did not occur at all (3/11pairs). Stimulation with angiotensin (Ang II) lowered the pacing threshold for CaT alternans (from 1.71±0.08 to 1.49±0.14 Hz) and enhanced the degree of alternans (increased alternans ratio), presumably through activation of IP3 receptor-induced Ca release. Under control conditions cell pairs spontaneously switched between periods of concordant and discordant CaT alternans. Concordant and discordant CaT alternans between cell pairs led to intercellular heterogeneity in the CaT amplitude resulting in beat-to-beat intercellular Ca gradients. Ang II further enhanced these intercellular Ca gradients. In Langendorff perfused rabbit hearts pacing-induced electrical alternans were recorded with atrial bipolar electrograms and multielectrode mapping of the epicardial surface. The data revealed a high temporal correlation between atrial alternans and episodes of AF: atrial electrical alternans in form of atrial T wave alternans triggered AF episodes, and AF induced by a burst pacing protocol was followed by episodes of atrial T wave alternans. Ang II perfusion enhanced tissue-wide atrial T wave variability, suggesting enhanced electrical tissue heterogeneity and possibly discordant alternans at tissue level.