Electrophysiological remodeling in heart failure

Wang, Yanggan; Hill, Joseph A.

doi:10.1016/j.yjmcc.2010.01.009

Cited by 101 publications

(103 citation statements)

References 254 publications

(249 reference statements)

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“…It has been shown that heart failure originates at the cellular scale [28,29,30]. Alterations in ionic currents and calcium handling lead to a prolonged action potential, a lower …”

Section: Heart Failurementioning

confidence: 99%

Multiscale model of the human cardiovascular system: Description of heart failure and comparison of contractility indices

Kosta

Negroni

Lascano

et al. 2017

Mathematical Biosciences

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A multiscale model of the cardiovascular system is presented. Hemodynamics is described by a lumped parameter model, while heart contraction is described at the cellular scale. An electrophysiological model and a mechanical model were coupled and adjusted so that the pressure and volume of both ventricles are linked to the force and length of a halfsarcomere. Particular attention was paid to the extreme values of the sarcomere length, which must keep physiological values. This model is able to reproduce healthy behavior, preload variations experiments, and ventricular failure. It also allows to compare the relevance of standard cardiac contractility indices. This study shows that the theoretical gold standard for assessing cardiac contractility, namely the end-systolic elastance, is actually load-dependent and therefore not a reliable index of cardiac contractility.

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“…It has been shown that heart failure originates at the cellular scale [28,29,30]. Alterations in ionic currents and calcium handling lead to a prolonged action potential, a lower …”

Section: Heart Failurementioning

confidence: 99%

Multiscale model of the human cardiovascular system: Description of heart failure and comparison of contractility indices

Kosta

Negroni

Lascano

et al. 2017

Mathematical Biosciences

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“…Because transmural gradients of repolarization are major factors influencing vulnerability to cardiac arrhythmias, 84,119,120 proper establishment and maintenance of electric gradients within the ventricular wall are clearly of great interest and importance. In particular, enhanced dispersion of repolarization is associated with several forms of lifethreatening reentrant and torsade-related ventricular arrhythmias, as occur in long-QT, short-QT, and Brugada syndromes, as well as catecholaminergic polymorphic ventricular tachycardia.…”

Section: Relationship Of Irx Genes To Cardiovascular Diseasementioning

confidence: 99%

“…84 In addition, heart disease is accompanied by electric remodeling, which is usually characterized by elevated heterogeneity of repolarization and increased susceptibility to arrhythmia. 120 Interestingly, reduced transmural repolarization gradients can also occur in some heart failure patients, 121 which may explain the increased susceptibility of Irx5 KO mice to arrhythmias, although these mice also show reduced refractoriness, 16 a condition strongly linked to arrhythmia vulnerability. 122 Thus, it is conceivable that changes in expression or mutations of IRX5 may be linked to cardiac arrhythmia in human.…”

Section: Relationship Of Irx Genes To Cardiovascular Diseasementioning

confidence: 99%

Iroquois Homeodomain Transcription Factors in Heart Development and Function

Kim

Rosén²,

Bruneau³

et al. 2012

Circulation Research

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Numerous cardiac transcription factors play overlapping roles in both the specification and proliferation of the cardiac tissues and chambers during heart development. It has become increasingly apparent that cardiac transcription factors also play critical roles in the regulation of expression of many functional genes in the prenatal and postnatal hearts. Accordingly, mutations of cardiac transcription factors cannot only result in congenital heart defects but also alter heart function thereby predisposing to heart disease and cardiac arrhythmias. In this review, we summarize the roles of Iroquois homeobox (Irx) family of transcription factors in heart development and function. In all, 6 Irx genes are expressed with distinct and overlapping patterns in the mammalian heart. Studies in several animal models demonstrate that Irx genes are important for the establishment of ventricular chamber properties, the ventricular conduction system, as well as heterogeneity of the ventricular repolarization Key Words: Iroquois homeobox Ⅲ cardiac transcription factor Ⅲ cardiac development T he heart is the first functional organ formed in the mammalian embryo in order to provide the necessary nutrients for growth and development. 1 Throughout life, the contraction sequence of the heart in each beat is orchestrated by well-defined electric activation patterns designed to enable efficient mechanical pumping of blood. Electric impulses begin in the auto-rhythmic cells of the sinoatrial node and propagate to the atria, thereby initiating contraction and blood propulsion into the relaxed and compliant ventricles. The electric impulses then proceed with highly controlled delay to the ventricles via the specialized ventricular conduction system (VCS), comprising sequentially the atrioventricular node, His bundles, left and right bundle branches, and Purkinje fiber network. Electrical stimulation of the VCS ultimately results in highly ordered ventricular contractions proceeding from the apex toward the base as well as from the endomyocardium to epimyocardium, 2,3 thus enabling efficient blood ejection into the systemic and pulmonary circulations. The ventricles then repolarize and relax in reverse order from epimyocardium to endomyocardium and from the base toward the apex.Efficient heart function requires the precise and harmonious union of structure and function, which is achieved by precisely controlled patterns of gene expression within different cardiac regions at developmental stages. For example, in the early embryo, cardiac transcription factors (TFs) such as Nkx2-5, 4 Gata, 5 Hand, 6 Nfat, 7 and the T-box family members 8 regulate many key aspects of heart development, including cardiac chamber septation, valve formation, and outflow tract morphogenesis. Consequently, mutations in these TFs are directly associated with several congenital heart diseases. 9 On the other hand, some of these same genes control expression of key functional genes regulating contractile and electric properties of the mature heart. 10 -13...

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“…The mechanical and electrical activation of the heart is in part dependent on the spatial distribution of GJs (22). Changes in GJ patterning and expression level can result in the development of arrhythmias in numerous cardiovascular diseases (23)(24)(25). The alteration in the expression level and spatial distribution of Cx43 in the hypertrophic myocardium suggests that this protein is influenced by ventricular remodeling (18).…”

Section: A B C D Ementioning

confidence: 99%

Reduction of isoproterenol-induced cardiac hypertrophy and modulation of myocardial connexin43 by a KATP channel agonist

Sun

Wang

Hao

et al. 2014

Molecular Medicine Reports

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Abstract. Cardiac hypertrophy is a compensatory mechanism that occurs in conjunction with cardiovascular diseases. Although hypertrophy of the myocardium provides certain benefits during the early stages of cardiovascular disease, prolonged hypertrophy is potentially harmful to the heart and can result in arrhythmia and heart failure. The aim of this study was to investigate whether an ATP-sensitive K + (K ATP ) channel agonist was capable of reducing isoproterenol (Iso)-induced cardiac hypertrophy and modulating myocardial connexin43 (Cx43) expression. Fifty male Sprague Dawley rats were randomly assigned to five groups: Normal, vehicle, nicorandil, glibenclamide and nicorandil plus glibenclamide. Rats in the four treatment groups received Iso injection for seven days, followed by administration with saline, nicorandil, glibenclamide or a combination of nicorandil and glibenclamide, respectively, for four weeks. Cardiac hypertrophy was then evaluated by measuring body weight, heart weight and left-ventricular weight, and plasma B-type natriuretic peptide levels were evaluated by ELISA. Immunocytochemistry and a reverse transcription-polymerase chain reaction were performed to detect the spatial distribution and gene expression of myocardial Cx43, respectively. The K ATP channel agonist nicorandil markedly attenuated the degree of myocardial hypertrophy induced by Iso as compared with the vehicle group. Myocardial Cx43 expression was significantly decreased and redistributed following cardiac hypertrophy. The decrease and redistribution of Cx43 was reduced following treatment with the K ATP channel agonist nicorandil. Addition of the K ATP channel blocker glibenclamide eliminated the beneficial effects of nicorandil against hypertrophy and on connexin43.In conclusion, the present study indicated that chronic use of K ATP channel agonists following cardiac hypertrophy can attenuate ventricular remodeling and upregulate the expression level and spatial distribution of Cx43.

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Electrophysiological remodeling in heart failure

Cited by 101 publications

References 254 publications

Multiscale model of the human cardiovascular system: Description of heart failure and comparison of contractility indices

Multiscale model of the human cardiovascular system: Description of heart failure and comparison of contractility indices

Iroquois Homeodomain Transcription Factors in Heart Development and Function

Reduction of isoproterenol-induced cardiac hypertrophy and modulation of myocardial connexin43 by a KATP channel agonist

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