Molecular and Electrophysiological Mechanisms Underlying Cardiac Arrhythmogenesis in Diabetes Mellitus

Tse, Gary; Lai, Eric; Tse, Vivian; Yeo, Jie Ming

doi:10.1155/2016/2848759

Cited by 70 publications

(67 citation statements)

References 87 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Repolarization abnormalities can result in early or delayed afterdepolarizations, which can initiate triggered activity when their magnitudes are sufficiently large to reach the threshold potential for sodium channel reactivation. They can also increase the dispersion of repolarization, promoting unidirectional conduction block and reentry 27, 28…”

Section: Discussionmentioning

confidence: 99%

“…They can also increase the dispersion of repolarization, promoting unidirectional conduction block and reentry. 27,28 Several oxidative stress mechanisms have been proposed to explain the development and perpetuation of AF in the context of diabetes mellitus. 29 An excellent study demonstrated that maximal capacity for mitochondrial oxidation of palmitoyl-carnitine is decreased while mitochondrial H 2 O 2 emission during oxidation of carbohydrate-and lipid-based substrates is increased, corresponding to increased local oxidative stress in the tissue, demonstrating mitochondria to be the main source of ROS.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Xanthine Oxidase Inhibitor Allopurinol Prevents Oxidative Stress‐Mediated Atrial Remodeling in Alloxan‐Induced Diabetes Mellitus Rabbits

Yang

Zhao

Qiu

et al. 2018

JAHA

Self Cite

View full text Add to dashboard Cite

BackgroundThere are several mechanisms, including inflammation, oxidative stress and abnormal calcium homeostasis, involved in the pathogenesis of atrial fibrillation. In diabetes mellitus (DM), increased oxidative stress may be attributable to higher xanthine oxidase activity. In this study, we examined the relationship between oxidative stress and atrial electrical and structural remodeling, and calcium handling abnormalities, and the potential beneficial effects of the xanthine oxidase inhibitor allopurinol upon these pathological changes.Methods and ResultsNinety rabbits were randomly and equally divided into 3 groups: control, DM, and allopurinol‐treated DM group. Echocardiographic and hemodynamic assessments were performed in vivo. Serum and tissue markers of oxidative stress and atrial fibrosis, including the protein expression were examined. Atrial interstitial fibrosis was evaluated by Masson trichrome staining. ICaL was measured from isolated left atrial cardiomyocytes using voltage‐clamp techniques. Confocal microscopy was used to detect intracellular calcium transients. The Ca2+ handling protein expression was analyzed by Western blotting. Mitochondrial‐related proteins were analyzed as markers of mitochondrial function. Compared with the control group, rabbits with DM showed left ventricular hypertrophy, increased atrial interstitial fibrosis, oxidative stress and fibrosis markers, ICaL and intracellular calcium transient, and atrial fibrillation inducibility. These abnormalities were alleviated by allopurinol treatment.ConclusionsAllopurinol, via its antioxidant effects, reduces atrial mechanical, structural, ion channel remodeling and mitochondrial synthesis abnormalities induced by DM‐related increases in oxidative stress.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Xanthine Oxidase Inhibitor Allopurinol Prevents Oxidative Stress‐Mediated Atrial Remodeling in Alloxan‐Induced Diabetes Mellitus Rabbits

Yang

Zhao

Qiu

et al. 2018

JAHA

Self Cite

View full text Add to dashboard Cite

show abstract

“…The mechanisms of arrhythmogenesis have been studied using animal models as they permit the use of genetic or pharmacological manipulation to study the consequences of ion channel abnormalities (19,20,22,23,44–46). In the present study, arrhythmogenic effects of hyperkalemia were examined in Langendorff-perfused mouse hearts.…”

Section: Discussionmentioning

confidence: 99%

Anti-arrhythmic effects of hypercalcemia in hyperkalemic, Langendorff-perfused mouse hearts

et al. 2016

Self Cite

View full text Add to dashboard Cite

The present study examined the ventricular arrhythmic and electrophysiological properties during hyperkalemia (6.3 mM [K+] vs. 4 mM in normokalemia) and anti-arrhythmic effects of hypercalcemia (2.2 mM [Ca2+]) in Langendorff-perfused mouse hearts. Monophasic action potential recordings were obtained from the left ventricle during right ventricular pacing. Hyperkalemia increased the proportion of hearts showing provoked ventricular tachycardia (VT) from 0 to 6 of 7 hearts during programmed electrical stimulation (Fisher's exact test, P<0.05). It shortened the epicardial action potential durations (APDx) at 90, 70, 50 and 30% repolarization and ventricular effective refractory periods (VERPs) (analysis of variance, P<0.05) without altering activation latencies. Endocardial APDx and VERPs were unaltered. Consequently, ∆APDx (endocardial APDx-epicardial APDx) was increased, VERP/latency ratio was decreased and critical intervals for reexcitation (APD90-VERP) were unchanged. Hypercalcemia treatment exerted anti-arrhythmic effects during hyperkalemia, reducing the proportion of hearts showing VT to 1 of 7 hearts. It increased epicardial VERPs without further altering the remaining parameters, returning VERP/latency ratio to normokalemic values and also decreased the critical intervals. In conclusion, hyperkalemia exerted pro-arrhythmic effects by shortening APDs and VERPs. Hypercalcemia exerted anti-arrhythmic effects by reversing VERP changes, which scaled the VERP/latency ratio and critical intervals.

show abstract

“…Pre-clinical models have been useful for the studying the mechanisms of cardiac arrhythmogenesis and provide a platform for testing the arrhythmogenic potential of drugs [29], [37], [39], [40], [41], [42], [43], [44], [45], [46], [47]. Experiments in these systems have demonstrated different arrhythmic risk markers, such as increased TDR given by the maximum APD difference across the myocardial wall [48], increased critical interval for re-excitation given by the APD-ERP difference [23], [49], [50], [51], shortened λ and reduced λ-TRIAD (which is based on λ and repolarization properties of triangulation, reverse use dependence, instability and dispersion: TRIaD) [52].…”

Section: Introductionmentioning

confidence: 99%

Electrophysiological mechanisms of long and short QT syndromes

Tse

Chan

Keung

et al. 2017

IJC Heart & Vasculature

Self Cite

View full text Add to dashboard Cite

The QT interval on the human electrocardiogram is normally in the order of 450 ms, and reflects the summated durations of action potential (AP) depolarization and repolarization of ventricular myocytes. Both prolongation and shortening in the QT interval have been associated with ventricular tachy-arrhythmias, which predispose affected individuals to sudden cardiac death. In this article, the molecular determinants of the AP duration and the causes of long and short QT syndromes (LQTS and SQTS) are explored. This is followed by a review of the recent advances on their arrhythmogenic mechanisms involving reentry and/or triggered activity based on experiments conducted in mouse models. Established and novel clinical risk markers based on the QT interval for the prediction of arrhythmic risk and cardiovascular mortality are presented here. It is concluded by a discussion on strategies for the future rational design of anti-arrhythmic agents.

show abstract

Molecular and Electrophysiological Mechanisms Underlying Cardiac Arrhythmogenesis in Diabetes Mellitus

Cited by 70 publications

References 87 publications

Xanthine Oxidase Inhibitor Allopurinol Prevents Oxidative Stress‐Mediated Atrial Remodeling in Alloxan‐Induced Diabetes Mellitus Rabbits

Xanthine Oxidase Inhibitor Allopurinol Prevents Oxidative Stress‐Mediated Atrial Remodeling in Alloxan‐Induced Diabetes Mellitus Rabbits

Anti-arrhythmic effects of hypercalcemia in hyperkalemic, Langendorff-perfused mouse hearts

Electrophysiological mechanisms of long and short QT syndromes

Contact Info

Product

Resources

About