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• W2113200468 abstract "In spite of its potential impact on simulation results, the problem of setting the appropriate Ca 2+ concentration ([Ca 2+ ] o ) in computational cardiac models has not yet been properly considered. Usually [Ca 2+ ] o values are derived from in vitro electrophysiology. Unfortunately, [Ca 2+ ] o in the experiments is set significantly far (1.8 or 2 mM) from the physiological [Ca 2+ ] in blood (1.0–1.3 mM). We analysed the inconsistency of [Ca 2+ ] o among in vivo , in vitro and in silico studies and the dependence of cardiac action potential (AP) duration (APD) on [Ca 2+ ] o . Laboratory measurements confirmed the difference between standard extracellular solutions and normal blood [Ca 2+ ]. Experimental data on human atrial cardiomyocytes confirmed literature data, demonstrating an inverse relationship between APD and [Ca 2+ ] o . Sensitivity analysis of APD on [Ca 2+ ] o for five of the most used cardiac cell models was performed. Most of the models responded with AP prolongation to increases in [Ca 2+ ] o , i.e. opposite to the AP shortening observed in vitro and in vivo. Modifications to the Ten Tusscher–Panfilov model were implemented to demonstrate that qualitative consistency among in vivo , in vitro and in silico studies can be achieved. The Courtemanche atrial model was used to test the effect of changing [Ca 2+ ] o on quantitative predictions about the effect of K + current blockade. The present analysis suggests that (i) [Ca 2+ ] o in cardiac AP models should be changed from 1.8 to 2 mM to approximately 1.15 mM in order to reproduce in vivo conditions, (ii) the sensitivity to [Ca 2+ ] o of ventricular AP models should be improved in order to simulate real conditions, (iii) modifications to the formulation of Ca 2+ -dependent I CaL inactivation can make models more suitable to analyse AP when [Ca 2+ ] o is set to lower physiological values, and (iv) it could be misleading to use non-physiological high [Ca 2+ ] o when the quantitative analysis of in vivo pathophysiological mechanisms is the ultimate aim of simulation." @default.
• W2113200468 created "2016-06-24" @default.
• W2113200468 creator A5009600398 @default.
• W2113200468 creator A5060301654 @default.
• W2113200468 creator A5074039900 @default.
• W2113200468 date "2009-06-13" @default.
• W2113200468 modified "2023-10-18" @default.
• W2113200468 title "From <i>in vivo</i> plasma composition to <i>in vitro</i> cardiac electrophysiology and <i>in silico</i> virtual heart: the extracellular calcium enigma" @default.
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• W2113200468 doi "https://doi.org/10.1098/rsta.2009.0032" @default.
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