Investigation of the mechanisms underlying cardiac alternans - insights from a computational study

Cardiac alternans is potentially associated with cardiac arrhythmia. Two forms of Cardiac alternans, action potential (AP) and Ca²⁺ transient (CaT) alternans are believed to be strongly correlated; however, the primary mechanisms underlying the occurrence of cardiac alternans are still unclear. In this study, a computational model of human ventricular cells was implemented to simulate cardiac alternans. By utilizing AP-clamp protocol, results showed that CaT alternans were generated at fast pacing rates, but absence at slow rates irrespective of AP alternans, suggesting that CaT alternans proceeded before AP alternans. By inhibiting the intracellular Ca²⁺ release from the sarcoplasmic reticulum (SR), CaT alternans were abolished, demonstrating a crucial role of the intracellular Ca²⁺ handling dynamics in genesis of cardiac alternans. Furthermore, ICaL and the SR content were analysed during the time courses of AP alternans. CaT alternans were observed without apparent association with alternating ICaL, but closely related to the alteration of the SR content. Our simulation data suggests that the leading cause of cardiac alternans in the human ventricle is CaT alternans, while AP alternans is the secondary result.