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Computational modeling of Takotsubo cardiomyopathy: effect of spatially varying β-adrenergic stimulation in the rat left ventricle

In Takotsubo cardiomyopathy, the left ventricle shows apical ballooning combined with basal hypercontractility. Both clinical observations in humans and recent experimental work on isolated rat ventricular myocytes suggest the dominant mechanisms of this syndrome are related to acute catecholamine o...

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Autores principales: Land, Sander, Niederer, Steven A., Louch, William E., Røe, Åsmund T., Aronsen, Jan Magnus, Stuckey, Daniel J., Sikkel, Markus B., Tranter, Matthew H., Lyon, Alexander R., Harding, Sian E., Smith, Nicolas P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Physiological Society 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4233305/
https://www.ncbi.nlm.nih.gov/pubmed/25239804
http://dx.doi.org/10.1152/ajpheart.00443.2014
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author Land, Sander
Niederer, Steven A.
Louch, William E.
Røe, Åsmund T.
Aronsen, Jan Magnus
Stuckey, Daniel J.
Sikkel, Markus B.
Tranter, Matthew H.
Lyon, Alexander R.
Harding, Sian E.
Smith, Nicolas P.
author_facet Land, Sander
Niederer, Steven A.
Louch, William E.
Røe, Åsmund T.
Aronsen, Jan Magnus
Stuckey, Daniel J.
Sikkel, Markus B.
Tranter, Matthew H.
Lyon, Alexander R.
Harding, Sian E.
Smith, Nicolas P.
author_sort Land, Sander
collection PubMed
description In Takotsubo cardiomyopathy, the left ventricle shows apical ballooning combined with basal hypercontractility. Both clinical observations in humans and recent experimental work on isolated rat ventricular myocytes suggest the dominant mechanisms of this syndrome are related to acute catecholamine overload. However, relating observed differences in single cells to the capacity of such alterations to result in the extreme changes in ventricular shape seen in Takotsubo syndrome is difficult. By using a computational model of the rat left ventricle, we investigate which mechanisms can give rise to the typical shape of the ventricle observed in this syndrome. Three potential dominant mechanisms related to effects of β-adrenergic stimulation were considered: apical-basal variation of calcium transients due to differences in L-type and sarco(endo)plasmic reticulum Ca(2+)-ATPase activation, apical-basal variation of calcium sensitivity due to differences in troponin I phosphorylation, and apical-basal variation in maximal active tension due to, e.g., the negative inotropic effects of p38 MAPK. Furthermore, we investigated the interaction of these spatial variations in the presence of a failing Frank-Starling mechanism. We conclude that a large portion of the apex needs to be affected by severe changes in calcium regulation or contractile function to result in apical ballooning, and smooth linear variation from apex to base is unlikely to result in the typical ventricular shape observed in this syndrome. A failing Frank-Starling mechanism significantly increases apical ballooning at end systole and may be an important additional factor underpinning Takotsubo syndrome.
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spelling pubmed-42333052014-11-21 Computational modeling of Takotsubo cardiomyopathy: effect of spatially varying β-adrenergic stimulation in the rat left ventricle Land, Sander Niederer, Steven A. Louch, William E. Røe, Åsmund T. Aronsen, Jan Magnus Stuckey, Daniel J. Sikkel, Markus B. Tranter, Matthew H. Lyon, Alexander R. Harding, Sian E. Smith, Nicolas P. Am J Physiol Heart Circ Physiol Integrative Cardiovascular Physiology and Pathophysiology In Takotsubo cardiomyopathy, the left ventricle shows apical ballooning combined with basal hypercontractility. Both clinical observations in humans and recent experimental work on isolated rat ventricular myocytes suggest the dominant mechanisms of this syndrome are related to acute catecholamine overload. However, relating observed differences in single cells to the capacity of such alterations to result in the extreme changes in ventricular shape seen in Takotsubo syndrome is difficult. By using a computational model of the rat left ventricle, we investigate which mechanisms can give rise to the typical shape of the ventricle observed in this syndrome. Three potential dominant mechanisms related to effects of β-adrenergic stimulation were considered: apical-basal variation of calcium transients due to differences in L-type and sarco(endo)plasmic reticulum Ca(2+)-ATPase activation, apical-basal variation of calcium sensitivity due to differences in troponin I phosphorylation, and apical-basal variation in maximal active tension due to, e.g., the negative inotropic effects of p38 MAPK. Furthermore, we investigated the interaction of these spatial variations in the presence of a failing Frank-Starling mechanism. We conclude that a large portion of the apex needs to be affected by severe changes in calcium regulation or contractile function to result in apical ballooning, and smooth linear variation from apex to base is unlikely to result in the typical ventricular shape observed in this syndrome. A failing Frank-Starling mechanism significantly increases apical ballooning at end systole and may be an important additional factor underpinning Takotsubo syndrome. American Physiological Society 2014-09-19 2014-11-15 /pmc/articles/PMC4233305/ /pubmed/25239804 http://dx.doi.org/10.1152/ajpheart.00443.2014 Text en Copyright © 2014 the American Physiological Society Licensed under Creative Commons Attribution CC-BY 3.0 (http://creativecommons.org/licenses/by/3.0/deed.en_US) : © the American Physiological Society.
spellingShingle Integrative Cardiovascular Physiology and Pathophysiology
Land, Sander
Niederer, Steven A.
Louch, William E.
Røe, Åsmund T.
Aronsen, Jan Magnus
Stuckey, Daniel J.
Sikkel, Markus B.
Tranter, Matthew H.
Lyon, Alexander R.
Harding, Sian E.
Smith, Nicolas P.
Computational modeling of Takotsubo cardiomyopathy: effect of spatially varying β-adrenergic stimulation in the rat left ventricle
title Computational modeling of Takotsubo cardiomyopathy: effect of spatially varying β-adrenergic stimulation in the rat left ventricle
title_full Computational modeling of Takotsubo cardiomyopathy: effect of spatially varying β-adrenergic stimulation in the rat left ventricle
title_fullStr Computational modeling of Takotsubo cardiomyopathy: effect of spatially varying β-adrenergic stimulation in the rat left ventricle
title_full_unstemmed Computational modeling of Takotsubo cardiomyopathy: effect of spatially varying β-adrenergic stimulation in the rat left ventricle
title_short Computational modeling of Takotsubo cardiomyopathy: effect of spatially varying β-adrenergic stimulation in the rat left ventricle
title_sort computational modeling of takotsubo cardiomyopathy: effect of spatially varying β-adrenergic stimulation in the rat left ventricle
topic Integrative Cardiovascular Physiology and Pathophysiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4233305/
https://www.ncbi.nlm.nih.gov/pubmed/25239804
http://dx.doi.org/10.1152/ajpheart.00443.2014
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