Temporal alterations and cellular mechanisms of transmural repolarization during progression of mouse cardiac hypertrophy and failure

Shi, Chenxia; Wang, X.; Dong, Fang; Wang, Y.; Hui, Jie; Lin, Zexu; Yang, Jing; Xu, Yancheng

doi:10.1111/apha.12071

Cited by 18 publications

(20 citation statements)

References 43 publications

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“…The failing heart phenotype is characterized by distinct alterations in selected ion channels, changes in intracellular calcium cycling, alterations in cell-cell coupling proteins, enhanced interstitial fibrosis, and cellular hypertrophy [5]–[7]. Experimental studies in animal models provide evidence for enhanced repolarization gradients in the setting of the failing heart [8], [9] and these can promote reentrant arrhythmias. However, recent studies performed using explanted failing human hearts [6], [10], [11] provide little evidence for these enhanced repolarization gradients.…”

Section: Introductionmentioning

confidence: 99%

Electrophysiological and Structural Remodeling in Heart Failure Modulate Arrhythmogenesis. 2D Simulation Study

et al. 2014

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BackgroundHeart failure is operationally defined as the inability of the heart to maintain blood flow to meet the needs of the body and it is the final common pathway of various cardiac pathologies. Electrophysiological remodeling, intercellular uncoupling and a pro-fibrotic response have been identified as major arrhythmogenic factors in heart failure.ObjectiveIn this study we investigate vulnerability to reentry under heart failure conditions by incorporating established electrophysiological and anatomical remodeling using computer simulations.MethodsThe electrical activity of human transmural ventricular tissue (5 cm×5 cm) was simulated using the human ventricular action potential model Grandi et al. under control and heart failure conditions. The MacCannell et al. model was used to model fibroblast electrical activity, and their electrotonic interactions with myocytes. Selected degrees of diffuse fibrosis and variations in intercellular coupling were considered and the vulnerable window (VW) for reentry was evaluated following cross-field stimulation.ResultsNo reentry was observed in normal conditions or in the presence of HF ionic remodeling. However, defined amount of fibrosis and/or cellular uncoupling were sufficient to elicit reentrant activity. Under conditions where reentry was generated, HF electrophysiological remodeling did not alter the width of the VW. However, intermediate fibrosis and cellular uncoupling significantly widened the VW. In addition, biphasic behavior was observed, as very high fibrotic content or very low tissue conductivity hampered the development of reentry. Detailed phase analysis of reentry dynamics revealed an increase of phase singularities with progressive fibrotic components.ConclusionStructural remodeling is a key factor in the genesis of vulnerability to reentry. A range of intermediate levels of fibrosis and intercellular uncoupling can combine to favor reentrant activity.

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Section: Introductionmentioning

confidence: 99%

Electrophysiological and Structural Remodeling in Heart Failure Modulate Arrhythmogenesis. 2D Simulation Study

et al. 2014

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“…23 From a histopathological point of view, it has been shown that fiber disarray and/or fibrosis are correlated with the occurrence of TWA and VT in HCM. Kon-no et al 9 investigated TWA in 12 patients with HCM and LV hypertrophy and found that TWA may be related to an abnormal myocardial disarray and/or fibrosis.…”

Section: Discussionmentioning

confidence: 99%

Late gadolinium enhancement of cardiac magnetic resonance imaging indicates abnormalities of time-domain T-wave alternans in hypertrophic cardiomyopathy with ventricular tachycardia

Naka¹,

Sato²,

Oikawa³

et al. 2015

Heart Rhythm

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“…The abnormality that is most consistently found in animal models of cardiac hypertrophy is the prolongation of the APD [23–25]. Ca 2+ plays a key role in the excitation-contraction coupling and the activation of Ca 2+ -dependent signalling pathways.…”

Section: Discussionmentioning

confidence: 99%

Effects of Wenxin Keli on the Action Potential and L-Type Calcium Current in Rats with Transverse Aortic Constriction-Induced Heart Failure

Guo

et al. 2013

Evidence-Based Complementary and Alternative Medicine

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Objective. We investigated the effects of WXKL on the action potential (AP) and the L-type calcium current (I Ca-L) in normal and hypertrophied myocytes. Methods. Forty male rats were randomly divided into two groups: the control group and the transverse aortic constriction- (TAC-) induced heart failure group. Cardiac hypertrophy was induced by TAC surgery, whereas the control group underwent a sham operation. Eight weeks after surgery, single cardiac ventricular myocytes were isolated from the hearts of the rats. The APs and I Ca-L were recorded using the whole-cell patch clamp technique. Results. The action potential duration (APD) of the TAC group was prolonged compared with the control group and was markedly shortened by WXKL treatment in a dose-dependent manner. The current densities of the I Ca-L in the TAC group treated with 5 g/L WXKL were significantly decreased compared with the TAC group. We also determined the effect of WXKL on the gating mechanism of the I Ca-L in the TAC group. We found that WXKL decreased the I Ca-L by accelerating the inactivation of the channels and delaying the recovery time from inactivation. Conclusions. The results suggest that WXKL affects the AP and blocked the I Ca-L, which ultimately resulted in the treatment of arrhythmias.

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Temporal alterations and cellular mechanisms of transmural repolarization during progression of mouse cardiac hypertrophy and failure

Abstract: The two distinct TDR modes were revealed during the progression of mouse cardiac hypertrophy and failure, indicating that the remodelling of TDR depends on the stage of the disease.

Cited by 18 publications

References 43 publications

Electrophysiological and Structural Remodeling in Heart Failure Modulate Arrhythmogenesis. 2D Simulation Study

Electrophysiological and Structural Remodeling in Heart Failure Modulate Arrhythmogenesis. 2D Simulation Study

Late gadolinium enhancement of cardiac magnetic resonance imaging indicates abnormalities of time-domain T-wave alternans in hypertrophic cardiomyopathy with ventricular tachycardia

Effects of Wenxin Keli on the Action Potential and L-Type Calcium Current in Rats with Transverse Aortic Constriction-Induced Heart Failure

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