Simultaneous Quantification of Spatially Discordant Alternans in Voltage and Intracellular Calcium in Langendorff-Perfused Rabbit Hearts and Inconsistencies with Models of Cardiac Action Potentials and Ca Transients

Frontiers in Physiology
Ilija UzelacFlavio H Fenton

Abstract

Rationale: Discordant alternans, a phenomenon in which the action potential duration (APDs) and/or intracellular calcium transient durations (CaDs) in different spatial regions of cardiac tissue are out of phase, present a dynamical instability for complex spatial dispersion that can be associated with long-QT syndrome (LQTS) and the initiation of reentrant arrhythmias. Because the use of numerical simulations to investigate arrhythmic effects, such as acquired LQTS by drugs is beginning to be studied by the FDA, it is crucial to validate mathematical models that may be used during this process. Objective: In this study, we characterized with high spatio-temporal resolution the development of discordant alternans patterns in transmembrane voltage (Vm) and intracellular calcium concentration ([Cai](+2)) as a function of pacing period in rabbit hearts. Then we compared the dynamics to that of the latest state-of-the-art model for ventricular action potentials and calcium transients to better understand the underlying mechanisms of discordant alternans and compared the experimental data to the mathematical models representing Vm and [Cai](+2) dynamics. Methods and Results: We performed simultaneous dual optical mapping imaging of ...Continue Reading

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Citations

Dec 24, 2018·American Journal of Physiology. Heart and Circulatory Physiology·Haibo NiWayne R Giles
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Sep 8, 2021·Frontiers in Physiology·Manuel Marina-BreysseDavid Filgueiras-Rama
Dec 31, 2021·Biophysical Journal·D'Artagnan GreeneYohannes Shiferaw

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