Autonomic Modulation in Cardiac Health and Disease

The heart is under continuous control by the autonomic nervous system, in which sympathetic and parasympathetic branches exert opposing influences on rate, rhythm and contractility. In health, a dynamic balance between sympathoexcitation and parasympathetic tone ensures adaptability to physiological demands, from exercise to rest. In disease states such as myocardial infarction, heart failure or arrhythmia, this balance becomes disrupted, leading to excessive sympathetic drive, reduced vagal activity and adverse remodelling of neural networks. Therapeutic strategies now aim to restore autonomic equilibrium through neuromodulatory interventions, including targeted nerve blockade, electrical stimulation of the vagus and novel non-invasive approaches. Advances in imaging and molecular mapping have revealed the structural plasticity of cardiac innervation, highlighting the potential to prevent sudden cardiac death by modulating neural inputs. Together, these insights underpin a rapidly evolving field that bridges fundamental neuroscience and clinical cardiology, with global implications for the management of cardiovascular morbidity and mortality.

Research from Nature Portfolio

Recent studies have demonstrated that photothermal neuromodulation using platinum-coated nanoshells in the NIR-II wavelength can achieve rapid, reversible activation and inhibition of autonomic fibres in large-animal models, offering precise control of heart rate and protection against acute ventricular arrhythmias. Foundational circuit-mapping work has applied tissue-clearing and optogenetic tools to delineate the three-dimensional organisation of sympathetic and parasympathetic inputs to the sinoatrial node, revealing distinct cholinergic and noradrenergic pathways that govern rate modulation. Seminal investigation into post-infarction innervation identified that blockade of protein tyrosine phosphatase σ enables sympathetic fibres to regenerate into scar tissue, normalising electrophysiological properties and markedly reducing arrhythmic susceptibility in preclinical models.

Autonomic Modulation in Cardiac Health and Disease publication trend

The graph below shows the total number of articles in autonomic modulation in cardiac health and disease across all publications each year (not limited to Nature Index journals).

Technical terms

Autonomic nervous system: the network of nerves regulating involuntary cardiac, vascular and organ functions.

Sympathetic tone: the baseline level of ‘fight or flight’ neural activity that increases heart rate and contractility.

Parasympathetic tone: the baseline level of ‘rest and digest’ activity, primarily mediated by the vagus nerve, that slows heart rate.

Photothermal neuromodulation: a method that uses light-absorbing materials to convert light into heat, thereby modulating neural excitability.

Vagal nerve stimulation: electrical activation of the vagus nerve to enhance parasympathetic output and stabilise cardiac electrophysiology.

Transient receptor potential vanilloid 1 (TRPV1): a temperature-sensitive ion channel involved in sensory signalling, including cardiac afferent pathways.

Neuropeptide Y (NPY): a sympathetic co-transmitter that modulates vascular tone, myocardial perfusion and arrhythmia susceptibility.

References

1. Pt nanoshells with a high NIR-II photothermal conversion efficiency mediates multimodal neuromodulation against ventricular arrhythmias. Nature Communications (2024).
2. Identification of peripheral neural circuits that regulate heart rate using optogenetic and viral vector strategies. Nature Communications (2019).
3. Autonomic Modulation for Cardiovascular Disease. Frontiers in Physiology (2020).
4. Targeting protein tyrosine phosphatase σ after myocardial infarction restores cardiac sympathetic innervation and prevents arrhythmias. Nature Communications (2015).
5. Quantification of sympathetic hyperinnervation and denervation after myocardial infarction by three-dimensional assessment of the cardiac sympathetic network in cleared transparent murine hearts. PLOS ONE (2017).
6. Cardiac TRPV1-afferent signaling promotes arrhythmogenic ventricular remodeling after myocardial infarction. JCI Insight (2020).
7. Neuropeptide-Y causes coronary microvascular constriction and is associated with reduced ejection fraction following ST-elevation myocardial infarction. European Heart Journal (2019).
8. The cardiac sympathetic co-transmitter neuropeptide Y is pro-arrhythmic following ST-elevation myocardial infarction despite beta-blockade. European Heart Journal (2019).
9. Coronary Sinus Neuropeptide Y Levels and Adverse Outcomes in Patients With Stable Chronic Heart Failure. JAMA Cardiology (2020).