ArticleAmerican journal of physiology. Regulatory, integrative and comparative physiology2012
Neuromodulation targets intrinsic cardiac neurons to attenuate neuronally mediated atrial arrhythmias.
Article in American journal of physiology. Regulatory, integrative and comparative physiology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 52 citations in OpenAlex.
- Electrophysiology and 3D-imaging reveal properties of human intracardiac neurons and increased excitability with atrial fibrillation.The Journal of physiology · 2025Article
- Neurocardiology: translational advancements and potential.The Journal of physiology · 2025Review
- Cardiotoxicity Associated With a Low Doses of 5-FU Promotes Morphoquantitative Changes in the Intrinsic Cardiac Nervous System.Cardiovascular toxicology · 2025Article
- Neuropsychobiology of fear-induced bradycardia in humans: progress and pitfalls.Molecular psychiatry · 2024Review
- Cardiac Neuroanatomy and Fundamentals of Neurocardiology.Cardiac electrophysiology clinics · 2024Review
- Vagus nerve stimulation alleviates cardiac dysfunction and inflammatory markers during heart failure in rats.Autonomic neuroscience : basic & clinical · 2024Article
- Predicting Heart Cell Types by Using Transcriptome Profiles and a Machine Learning Method.Life (Basel, Switzerland) · 2022Article
- Autonomic imbalance and atrial ectopic activity-a pathophysiological and clinical view.Frontiers in physiology · 2022Review
- Autonomic modulation of ventricular electrical activity: recent developments and clinical implications.Clinical autonomic research : official journal of the Clinical Autonomic Research Society · 2021Review
- The Intrinsic Cardiac Nervous System and Its Role in Cardiac Pacemaking and Conduction.Journal of cardiovascular development and disease · 2020Review
- Spinal cord neural network interactions: implications for sympathetic control of the porcine heart.American journal of physiology. Heart and circulatory physiology · 2020Article
- Androgen Effects on the Adrenergic System of the Vascular, Airway, and Cardiac Myocytes and Their Relevance in Pathological Processes.International journal of endocrinology · 2020Review
- Autonomic Modulation for Cardiovascular Disease.Frontiers in physiology · 2020Review
- Thoracic spinal cord neuromodulation obtunds dorsal root ganglion afferent neuronal transduction of the ischemic ventricle.American journal of physiology. Heart and circulatory physiology · 2019Article
- Calming the Nervous Heart: Autonomic Therapies in Heart Failure.Cardiac failure review · 2018Review
- Synaptic Plasticity in Cardiac Innervation and Its Potential Role in Atrial Fibrillation.Frontiers in physiology · 2018Review
- Application of animal and human PET in cardiac research.American journal of cardiovascular disease · 2018Review
- Influence of cardiac nerve status on cardiovascular regulation and cardioprotection.World journal of cardiology · 2017Review
- Premature Ventricular Contraction Coupling Interval Variability Destabilizes Cardiac Neuronal and Electrophysiological Control: Insights From Simultaneous Cardioneural Mapping.Circulation. Arrhythmia and electrophysiology · 2017Article
- Recurrent myocardial infarction: Mechanisms of free-floating adaptation and autonomic derangement in networked cardiac neural control.PloS one · 2017Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
Our objective was to determine whether atrial fibrillation (AF) results from excessive activation of intrinsic cardiac neurons (ICNs) and, if so, whether select subpopulations of neurons therein represent therapeutic targets for suppression of this arrhythmogenic potential. Trains of five electrical stimuli (0.3-1.2 mA, 1 ms) were delivered during the atrial refractory period to mediastinal nerves (MSN) on the superior vena cava to evoke AF. Neuroanatomical studies were performed by injecting the neuronal tracer DiI into MSN sites that induced AF. Functional studies involved recording of neuronal activity in situ from the right atrial ganglionated plexus (RAGP) in response to MSN stimulation (MSNS) prior to and following neuromodulation involving either preemptive spinal cord stimulation (SCS; T(1)-T(3), 50 Hz, 200-ms duration) or ganglionic blockade (hexamethonium, 5 mg/kg). The tetramethylindocarbocyanine perchlorate (DiI) neuronal tracer labeled a subset (13.2%) of RAGP neurons, which also colocalized with cholinergic or adrenergic markers. A subset of DiI-labeled RAGP neurons were noncholinergic/nonadrenergic. MSNS evoked an ∼4-fold increase in RAGP neuronal activity from baseline, which SCS reduced by 43%. Hexamethonium blocked MSNS-evoked increases in neuronal activity. MSNS evoked AF in 78% of right-sided MSN sites, which SCS reduced to 33% and hexamethonium reduced to 7%. MSNS-induced bradycardia was maintained with SCS but was mitigated by hexamethonium. We conclude that MSNS activates subpopulations of intrinsic cardiac neurons, thereby resulting in the formation of atrial arrhythmias leading to atrial fibrillation. Stabilization of ICN local circuit neurons by SCS or the local circuit and autonomic efferent neurons with hexamethonium reduces the arrhythmogenic potential.
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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.