Hypertrophy in Rat Virtual Left Ventricular Cells and Tissue

Kharche, Sanjay; Zhang, H.; Clayton, RA; Holden, Arun V.

doi:10.1007/11494621_16

Cited by 3 publications

(9 citation statements)

References 18 publications

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“…This is due mainly to hyperglycemia-induced fibrosis which results in dysfunction of the CCS in the diabetic heart (see Figure 2). Moreover, it was demonstrated by Zhang et al [18] that diabetes-induced fibrosis of the heart was associated with the reduction of potassium channel (HCN4), Ca v 1.3, Ca v 3.1 (calcium channel), NCX1, (sodium-calcium exchanger) and connexin (Cx45) protein expression in the sinoatrial node of the heart which in turn resulted in brady-arrhythmia and possibly SCD [18]. Moreover, reduced ryanodine (RyR2) and sodium-calcium exchanger (NCX1) protein expression in the atrio-ventricular junction of the heart (AVJ) is believed to contribute in part to the prolongation of the PR interval.…”

Section: Scd Due To Diabetes-induced Autonomic System Neuropathy and Brady-arrhythmiasmentioning

confidence: 86%

“…Moreover, diabetes can also downregulate the beta-adrenergic receptor in the myocardium which in turn synergizes the brady-arrhythmias leading to cessation of the heart or SCD. There is new evidence that diabetes-induced cardiomyopathy is common and there is an increased risk of arrhythmias as a result of dysfunction of the cardiac conduction system (CCS) [17,18]. This is due mainly to hyperglycemia-induced fibrosis which results in dysfunction of the CCS in the diabetic heart (see Figure 2).…”

Section: Scd Due To Diabetes-induced Autonomic System Neuropathy and Brady-arrhythmiasmentioning

confidence: 99%

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Mechanisms of Diabetes Mellitus-Induced Sudden Cardiac Death

Smail¹,

Howarth²,

Singh³

et al. 2020

Sudden Cardiac Death

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More than 450 million people worldwide have diabetes mellitus (DM), a metabolic disorder characterized by an increase in blood glucose level (hyperglycemia) that arises from insufficient insulin secretion or resistance to insulin’s action. More than 70% of individuals with chronic DM will develop cardiovascular diseases (CVDs) including atherosclerosis and coronary artery diseases (CADs), hypertension, cardiac arrhythmias, cardiomyopathy (heart failure), stroke, and chronic kidney disease. A significant number of these individuals will also succumb to sudden cardiac death (SCD). SCD usually occurs in early morning from abnormal heart rhythms or arrhythmias and ventricular fibrillation. When the pumping action of the heart becomes erratic, a reduction in oxygenated blood to the brain leads to unconsciousness and brain damage. SCD is independent of age and sex and positively correlates with impairment in cardiac metabolism, muscle damage, fibrosis, apoptosis, hypertrophy, ischemia, and deranged cation signaling. This review centers on mechanisms by which intracellular cations (Na+, K+, and Ca2+) handling, inflammation, and oxidative and carbonyl stresses due to diabetes-induced hyperglycemia can lead to the deterioration of excitation/contraction coupling (ECC), impaired contractility, arrhythmias, and SCD in DM patients. It also discusses the beneficial effects of exercise training to attenuate the risk of SCD.

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Section: Scd Due To Diabetes-induced Autonomic System Neuropathy and Brady-arrhythmiasmentioning

confidence: 86%

Section: Scd Due To Diabetes-induced Autonomic System Neuropathy and Brady-arrhythmiasmentioning

confidence: 99%

Mechanisms of Diabetes Mellitus-Induced Sudden Cardiac Death

Smail¹,

Howarth²,

Singh³

et al. 2020

Sudden Cardiac Death

View full text Add to dashboard Cite

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“…This model has been modified according to available experimental data from rat ventricular cells [3], under Sham and HP conditions. The LV hypotrophy that induced by HP was modeled following the work of Kharche et al [7] and then implemented in the HP electromechanical model.…”

Section: Discussionmentioning

confidence: 99%

“…Firstly, changes in the myofilament responses to Ca #$ [3] have been incorporated in Sham and HP models (not shown in this paper). Secondly, followed the work of Kharche et al, 2005 [7] and to simulate LV hypertrophy, changes include sodium channel current, &' , up-regulated (conductance increased by 8%), the outward transient potassium channel current, I to , down-regulated (conductance decreased by 35%), and sodium-calcium exchanger current up-regulated (the &'*' scaling factor increased by 5 %), with a 30% increase in the cell size and cell capacitance [7], all of which have been implemented in the hypertension model.…”

Section: Model Developmentmentioning

confidence: 99%

“…It has been found that HP induces a left ventricular (LV) hypertrophy, which causes remodeling of several ion channels as well as prolongs the ventricles depolarization [7]. Such remodeling has been reported in the ventricular myocytes of some mammal species such as rats where hypertrophy induces changes in the density of several currents including, &' , () and &'*' , in addition to changes in the cell size and the calcium sensitivity of Ltype #$ which is myofilament responses to #$ in the cardiac cell [7]. Therefore, to simulate hypotrophy, all these changes have been employed in the electromechanical model for human ventricular myocytes in the current paper.…”

Section: Introductionmentioning

confidence: 99%

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Modelling the Effects of Hypertension on Ventricle Cells of Human Heart

Naser¹,

Zhang²,

Zhang³

2019

2019 Computing in Cardiology Conference (CinC)

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Systemic hypertension (HP) is one of the key risk factors for evolving cardiac hypertrophy and heart failure (HF). Previous studies have shown that cardiac hypertrophy is associated with altered excitation-contraction (E-C) coupling and enhanced myocardial contraction, whilst HF is associated with diminished contractility.This study aimed to investigate the functional impact of hypertension on the cardiac mechanical dynamics and the contracting mechanisms of the left ventricular myocytes of human heart. An electromechanical model of human ventricular cell model developed by Adeniran et al. has been modified by incorporating available experimental data from rat ventricular cells under Sham (control) and HP conditions. Hypertrophy was modeled by incorporating experimental data of changes in I Na , I to , I NaCa , cell size and myofilament responses to Ca 2+ in the cardiac cell.Simulations showed that HP produced:1) prolongation of the action potential duration at 90% repolarization (APD 90 ) by approximately 4.7%; 2) an increase of the intracellular calcium concentration ([Ca 2+ ] i ) by 36%; 3) no marked change in the sarcomere length or the contractile force. Simulation results were consistent with experimental data, validating the HP model development and indicated the pro-arrhythmic effects of HP.

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Mechanisms underlying adaptation of action potential duration by pacing rate in rat myocytes

Sallé¹,

Kharche

Zhang

et al. 2008

Progress in Biophysics and Molecular Biology

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Heart rate is an essential determinant of cardiac performance. In rat ventricular myocytes, a sudden increase in rate yields to a prolongation of the action potential duration (APD). The mechanism underlying this prolongation is controversial: it has been proposed that the longer APD is due to either: (1) a decrease in K+ currents only or (2) an increase in Ca2+ current only. The aim of this study was to quantitatively investigate the contribution of Ca2+ and K+ currents in the adaptation of APD to pacing rate. Simulation using a mathematical model of ventricular rat cardiac cell model [Pandit, S.V., Clark, R.B., Giles, W.R., Demir, S.S., 2001. A mathematical model of action potential heterogeneity in adult rat left ventricular myocytes. Biophys. J. 81, 3029-3051] predicted a role in the prolongation of APD for K+ currents only. In patch clamp experiments, increasing the pacing rate leads to a significant increase in APD in both control and detubulated myocytes, although it was more marked in control than detubulated myocytes. Supporting the model prediction, we observed that increasing stimulation frequency leads to a decrease in K+ currents in voltage clamped rat ventricular myocytes (square and action potential waveforms), and to a similar extent in both cell types. We have also observed that frequency-dependent facilitation of Ca2+ current occurred in control cells but not in detubulated cells (square and action potential waveforms). From these experiments, we calculated that the relative contribution of Ca2+ and K+ currents to the longer APD following an increase in pacing rate is approximately 65% and approximately 35%, respectively. Therefore, in contrast to the model prediction, Ca2+ current has a significant role in the adaptation of APD to pacing rate. Finally, we have introduced a simplistic modification to the Pandit's model to account for the frequency-dependent facilitation of Ca2+ current.

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Hypertrophy in Rat Virtual Left Ventricular Cells and Tissue

Cited by 3 publications

References 18 publications

Mechanisms of Diabetes Mellitus-Induced Sudden Cardiac Death

Mechanisms of Diabetes Mellitus-Induced Sudden Cardiac Death

Modelling the Effects of Hypertension on Ventricle Cells of Human Heart

Mechanisms underlying adaptation of action potential duration by pacing rate in rat myocytes

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