Reference : Experimental assessment of a myocyte-based multiscale model of cardiac contractile dy...
Scientific journals : Article
Physical, chemical, mathematical & earth Sciences : Multidisciplinary, general & others
http://hdl.handle.net/2268/227845
Experimental assessment of a myocyte-based multiscale model of cardiac contractile dysfunction.
English
Lascano, Elena C. [> >]
Felice, Juan I. [> >]
Wray, Sandra [> >]
Kosta, Sarah mailto [Université de Liège - ULiège > Département d'astrophys., géophysique et océanographie (AGO) > Thermodynamique des phénomènes irréversibles >]
Dauby, Pierre mailto [Université de Liège - ULiège > Département d'astrophys., géophysique et océanographie (AGO) > Thermodynamique des phénomènes irréversibles >]
Cabrera-Fischer, Edmundo I. [> >]
Negroni, Jorge A. [> >]
2018
Journal of theoretical biology
456
16-28
No
International
0022-5193
1095-8541
England
[en] Cardiac contractile dysfunction ; Hemodynamics ; Multiscale model ; Myocyte contraction model ; Sheep experiments
[en] Cardiac contractile dysfunction (CD) is a multifactorial syndrome caused by different acute or progressive diseases which hamper assessing the role of the underlying mechanisms characterizing a defined pathological condition. Mathematical modeling can help to understand the processes involved in CD and analyze their relative impact in the overall response. The aim of this study was thus to use a myocyte-based multiscale model of the circulatory system to simulate the effects of halothane, a volatile anesthetic which at high doses elicits significant acute CD both in isolated myocytes and intact animals. Ventricular chambers built using a human myocyte model were incorporated into a whole circulatory system represented by resistances and capacitances. Halothane-induced decreased sarco(endo)plasmic reticulum Ca(2+) (SERCA2a) reuptake pump, transient outward K(+) (Ito), Na(+)-Ca(2+) exchanger (INCX) and L-type Ca(2+) channel (ICaL) currents, together with ryanodine receptor (RyR2) increased open probability (Po) and reduced myofilament Ca(2+) sensitivity, reproduced equivalent decreased action potential duration at 90% repolarization and intracellular Ca(2+) concentration at the myocyte level reported in the literature. In the whole circulatory system, model reduction in mean arterial pressure, cardiac output and regional wall thickening fraction was similar to experimental results in open-chest sheep subjected to acute halothane overdose. Effective model performance indicates that the model structure could be used to study other changes in myocyte targets eliciting CD.
http://hdl.handle.net/2268/227845
10.1016/j.jtbi.2018.07.038
Copyright (c) 2018. Published by Elsevier Ltd.

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