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- W4384920007 abstract "Disturbances in calcium homeostasis in a cardiac myocyte can lead to calcium-overload conditions and abnormal calcium releases, which occur primarily in the following two phases of the action potential (AP): (a) triggered or late calcium release (LCR) during the plateau phase; (b) spontaneous calcium release (SCR) during the diastolic interval (DI). Experimental and numerical studies of LCRs and SCRs have suggested that these abnormal calcium releases can lead to triggered excitations and, thence to life-threatening ventricular arrhythmias. We explore this suggestion in detail by building on our work in the previous accompanying Paper I, where we have studied abnormal calcium releases and delayed afterdepolarizations (DADs) in two state-of-the-art mathematical models for human ventricular myocytes. Here, we carry out a detailed textit{in-silico} study of one of these models, namely, the ten Tusscher-Panfilov TP06~cite{ten2006alternans} model. We increase the L-type Ca-channel current $I_{rm{CaL}}$ to trigger LCRs, and calcium leak through the ryanodine receptor (RyR) to trigger SCRs, in the myocyte. We then perform multiscale simulations of coupled TP06-model myocytes in tissue in one-, two-, and three-dimensional (1D, 2D, and 3D) domains, with clumps of DAD-capable myocytes, to demonstrate how these clumps precipitate premature ventricular complexes (PVCs) that lead, in turn, to fibrillatory excitations like spiral and scroll waves. We examine possible pharmacological implications of our study for the class of ventricular arrhythmias that result from Catextsuperscript{2+} overload." @default.
- W4384920007 created "2023-07-21" @default.
- W4384920007 creator A5007147817 @default.
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- W4384920007 date "2023-07-14" @default.
- W4384920007 modified "2023-09-24" @default.
- W4384920007 title "Multiscale studies of delayed afterdepolarizations II: Calcium-overload-induced ventricular arrhythmias" @default.
- W4384920007 doi "https://doi.org/10.48550/arxiv.2307.10113" @default.
- W4384920007 hasPublicationYear "2023" @default.
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