Inferring the Cellular Origin of Voltage and Calcium Alternans from the Spatial Scales of Phase Reversal during Discordant Alternans

摘要: Beat-to-beat alternation of the action potential duration (APD) in paced cardiac cells has been linked to onset lethal arrhythmias. Both experimental and theoretical studies have shown that alternans at single cell level can be caused by unstable membrane voltage (Vm) dynamics steep APD-restitution, or intracellular calcium (Ca) cycling high sensitivity Ca release from sarcoplasmic reticulum on load. Identifying which these two mechanisms is primary cause cellular alternans, however, remained difficult since Vm are bidirectionally coupled. Here, we use numerical simulations a physiologically detailed ionic model show origin inferred measuring length scales over APD Cai reverse phase during spatially discordant alternans. The main conclusion comparable few millimeters equal when driven restitution, but differ markedly predominantly cycling. In latter case, still reverses millimeter tissue scale due electrotonic coupling, while submillimeter scale. These results experimentally accessible measurements used shed light