ArticleJCI insight2023
Heterogeneous cardiac sympathetic innervation gradients promote arrhythmogenesis in murine dilated cardiomyopathy.
Article in JCI insight, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 21 citations in OpenAlex.
- Shock Induced Endotheliopathy and High Trauma Mortality-Fight-or-Flight Response Revisited.International journal of molecular sciences · 2026Review
- Neurovascular interactions in the ageing heart.Nature reviews. Cardiology · 2026Review
- Redefining Sudden Cardiac Death Risk Stratification in Dilated Cardiomyopathy: An Integrative Approach.Reviews in cardiovascular medicine · 2026Review
- Phospho-mimic βIII-tubulin rescues microtubule and cardiac defects in Duchenne muscular dystrophy mice.Journal of molecular and cellular cardiology · 2026Article
- Mechanical Dispersion in Dilated and Non-Dilated Left Ventricular Cardiomyopathy: A New Frontier in Arrhythmic Risk Prediction.Journal of clinical medicine · 2026Review
- Low-Dose Cardiac Radiation Improves Electrical Function and Reduces Ventricular Arrhythmogenesis in Mice With Nonischemic Cardiomyopathy.JACC. Clinical electrophysiology · 2026Article
- A model of β-adrenergic stimulation in human ventricular cells for tissue-scale simulations of sympathetically modulated tachycardias.The Journal of physiology · 2026Article
- Acute arrhythmias in a long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency mouse model.American journal of physiology. Heart and circulatory physiology · 2026Article
- Noradrenergic and cholinergic innervation of the normal human heart and changes associated with cardiomyopathy.Anatomical record (Hoboken, N.J. : 2007) · 2026Article
- Autonomic nervous system modulation in arrhythmias: mechanisms and therapeutic advances.Frontiers in physiology · 2026Review
- Regulation of Cardiac Function by the Autonomic Nervous System.Physiology (Bethesda, Md.) · 2025Review
- Stellate Ganglia: A Key Therapeutic Target for Malignant Ventricular Arrhythmia in Heart Disease.Circulation research · 2025Review
- Bayliss Starling Prize Lecture 2023: Neuropeptide-Y being 'unsympathetic' to the broken hearted.The Journal of physiology · 2025Article
- Neurocardiology: translational advancements and potential.The Journal of physiology · 2025Review
- Molecular and cellular neurocardiology in heart disease.The Journal of physiology · 2025Review
- Ultrastructure and cardiac impulse propagation: scaling up from microscopic to macroscopic conduction.The Journal of physiology · 2025Review
- Clinical neurocardiology: defining the value of neuroscience-based cardiovascular therapeutics - 2024 update.The Journal of physiology · 2025Review
- Hypertension-induced heart failure disrupts cardiac sympathetic innervation.American journal of physiology. Heart and circulatory physiology · 2024Article
- Review
- Sympathetic remodeling and altered angiotensin-converting enzyme 2 localization occur in patients with cardiac disease but are not exacerbated by severe COVID-19.Autonomic neuroscience : basic & clinical · 2024Article
Corrections and comments
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Authors and funding
18 authors at 7 institutions in 2 countries.
Funding
Abstract
Ventricular arrhythmias (VAs) in heart failure are enhanced by sympathoexcitation. However, radiotracer studies of catecholamine uptake in failing human hearts demonstrate a proclivity for VAs in patients with reduced cardiac sympathetic innervation. We hypothesized that this counterintuitive finding is explained by heterogeneous loss of sympathetic nerves in the failing heart. In a murine model of dilated cardiomyopathy (DCM), delayed PET imaging of sympathetic nerve density using the catecholamine analog [11C]meta-Hydroxyephedrine demonstrated global hypoinnervation in ventricular myocardium. Although reduced, sympathetic innervation in 2 distinct DCM models invariably exhibited transmural (epicardial to endocardial) gradients, with the endocardium being devoid of sympathetic nerve fibers versus controls. Further, the severity of transmural innervation gradients was correlated with VAs. Transmural innervation gradients were also identified in human left ventricular free wall samples from DCM versus controls. We investigated mechanisms underlying this relationship by in silico studies in 1D, 2D, and 3D models of failing and normal human hearts, finding that arrhythmogenesis increased as heterogeneity in sympathetic innervation worsened. Specifically, both DCM-induced myocyte electrical remodeling and spatially inhomogeneous innervation gradients synergistically worsened arrhythmogenesis. Thus, heterogeneous innervation gradients in DCM promoted arrhythmogenesis. Restoration of homogeneous sympathetic innervation in the failing heart may reduce VAs.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.