Repolarization alternans, the alternation of long and short action potential durations (APD), has been linked to the incidence of ventricular fibrillation and sudden cardiac death. Multiple heart diseases are associated with an increased vulnerability to alternans. It is known that cardiac remodelling in heart failure and other diseases alters both intracellular calcium release and reuptake within cardiomyocytes. Reduced reuptake capacity has been linked to alternans vulnerability. In the present study, the researchers aimed at characterizing how altered properties of the sarcoplasmic reticulum (SR) calcium release modulate alternans vulnerability. The researchers adapted Heijman–Rudy computer models of ventricular myocyte to obtain precise control over SR release dynamics and magnitude, allowing for the evaluation of these properties in alternans formation and suppression. The data shows that sufficiently increased calcium release may surprisingly prevent alternans via a mechanism linked to the functional depletion of junctional SR during release. The model also allowed to provide a detailed explanation of alternans formation. In conclusion, the study shows how altered dynamics and magnitude of SR calcium release modulate alternans vulnerability which could be exploited to develop strategies to reduce arrhythmia occurrence.
Modulation of cardiac alternans by altered sarcoplasmic reticulum calcium release: a simulation study
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