Altered parasympathetic nervous system regulation of the sinoatrial node in Akita diabetic mice

Krishnaswamy, Pooja S.; Egom, Emmanuel E.; Moghtadaei, Motahareh; Jansen, Hailey J.; Azer, John; Bogachev, Oleg; Mackasey, Martin; Robbins, Courtney; Rose, Robert A.

doi:10.1016/j.yjmcc.2015.02.024

Cited by 36 publications

(46 citation statements)

References 49 publications

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“…In addition, a 1.2 French octapolar electrophysiology catheter was inserted in the heart via the right jugular vein, as we have described previously2324. P wave duration and PR interval were measured from surface ECGs.…”

Section: Methodsmentioning

confidence: 99%

“…To investigate patterns of electrical conduction in the atria we used high resolution optical mapping in atrial preparations as we have described previously232425. Optical mapping was performed using the voltage sensitive dye di-4-ANEPPS (10 μM).…”

Section: Methodsmentioning

confidence: 99%

“…The level of fibrosis was quantified using ImageJ software as previously described2324. Total collagen content was measured using a hydroxyproline assay (Sigma-Aldrich) according to kit instructions.…”

Section: Methodsmentioning

confidence: 99%

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Atrial structure, function and arrhythmogenesis in aged and frail mice

Jansen

Moghtadaei

Mackasey

et al. 2017

Sci Rep

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Atrial fibrillation (AF) is prevalent in aging populations; however not all individuals age at the same rate. Instead, individuals of the same chronological age can vary in health status from fit to frail. Our objective was to determine the impacts of age and frailty on atrial function and arrhythmogenesis in mice using a frailty index (FI). Aged mice were more frail and demonstrated longer lasting AF compared to young mice. Consistent with this, aged mice showed longer P wave duration and PR intervals; however, both parameters showed substantial variability suggesting differences in health status among mice of similar chronological age. In agreement with this, P wave duration and PR interval were highly correlated with FI score. High resolution optical mapping of the atria demonstrated reduced conduction velocity and action potential duration in aged hearts that were also graded by FI score. Furthermore, aged mice had increased interstitial fibrosis along with changes in regulators of extracellular matrix remodelling, which also correlated with frailty. These experiments demonstrate that aging results in changes in atrial structure and function that create a substrate for atrial arrhythmias. Importantly, these changes were heterogeneous due to differences in health status, which could be identified using an FI.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Atrial structure, function and arrhythmogenesis in aged and frail mice

Jansen

Moghtadaei

Mackasey

et al. 2017

Sci Rep

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“…This may be related to autonomic dysregulation, with increased adrenergic drive with or without impairment of parasympathetic response. Thus, in Akita diabetic mice, the SA node is less responsive to acetylcholine because of a reduction in acetylcholine-activated K + current ( I K,ACh ), which is due to altered phosphoinositide 3-kinase (PI3K) signalling [76]. …”

Section: Diabetic Cardiomyopathy: Cardiac Electrophysiological Andmentioning

confidence: 99%

Molecular and Electrophysiological Mechanisms Underlying Cardiac Arrhythmogenesis in Diabetes Mellitus

Tse

Lai

Tse

et al. 2016

Journal of Diabetes Research

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Diabetes is a common endocrine disorder with an ever increasing prevalence globally, placing significant burdens on our healthcare systems. It is associated with significant cardiovascular morbidities. One of the mechanisms by which it causes death is increasing the risk of cardiac arrhythmias. The aim of this article is to review the cardiac (ion channel abnormalities, electrophysiological and structural remodelling) and extracardiac factors (neural pathway remodelling) responsible for cardiac arrhythmogenesis in diabetes. It is concluded by an outline of molecular targets for future antiarrhythmic therapy for the diabetic population.

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“…17,28,29 Optical mapping was done using the voltage sensitive dye di-4-ANEPPS (10 μmol/L) and blebbistatin (10 μmol/L) to suppress contractile activity. All analyses were performed using custom software.…”

Section: High-resolution Optical Mappingmentioning

confidence: 99%

Effects of Wild-Type and Mutant Forms of Atrial Natriuretic Peptide on Atrial Electrophysiology and Arrhythmogenesis

Hua

MacLeod

Polina

et al. 2015

Circ: Arrhythmia and Electrophysiology

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Background-Atrial natriuretic peptide (ANP) is a hormone with numerous beneficial cardiovascular effects. Recently, a mutation in the ANP gene, which results in the generation of a mutant form of ANP (mANP), was identified and shown to cause atrial fibrillation in people. The mechanism(s) through which mANP causes atrial fibrillation is unknown. Our objective was to compare the effects of wild-type ANP and mANP on atrial electrophysiology in mice and humans. Methods and Results-Action potentials (APs), L-type Ca 2+ currents (I Ca,L ), and Na + current were recorded in atrial myocytes from wild-type or natriuretic peptide receptor C knockout (NPR-C −/− ) mice. In mice, ANP and mANP (10-100 nmol/L) had opposing effects on atrial myocyte AP morphology and I Ca,L . ANP increased AP upstroke velocity (V max ), AP duration, and I Ca,L similarly in wild-type and NPR-C −/− myocytes. In contrast, mANP decreased V max , AP duration, and I Ca,L , and these effects were completely absent in NPR-C −/− myocytes. ANP and mANP also had opposing effects on I Ca,L in human atrial myocytes. In contrast, neither ANP nor mANP had any effect on Na + current in mouse atrial myocytes. Optical mapping studies in mice demonstrate that ANP sped electric conduction in the atria, whereas mANP did the opposite and slowed atrial conduction. Atrial pacing in the presence of mANP induced arrhythmias in 62.5% of hearts, whereas treatment with ANP completely prevented the occurrence of arrhythmias. Conclusions-These findings provide mechanistic insight into how mANP causes atrial fibrillation and demonstrate that wildtype ANP is antiarrhythmic.

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Altered parasympathetic nervous system regulation of the sinoatrial node in Akita diabetic mice

Cited by 36 publications

References 49 publications

Atrial structure, function and arrhythmogenesis in aged and frail mice

Atrial structure, function and arrhythmogenesis in aged and frail mice

Molecular and Electrophysiological Mechanisms Underlying Cardiac Arrhythmogenesis in Diabetes Mellitus

Effects of Wild-Type and Mutant Forms of Atrial Natriuretic Peptide on Atrial Electrophysiology and Arrhythmogenesis

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