About

Jeffrey Ardell is a Professor-in-Residence in the Departments of Medicine and Anesthesiology at the University of California Los Angeles. His research focuses on neurocardiology, autonomic regulation, and neuromodulation therapies related to cardiovascular health. Ardell has contributed extensively to understanding the neural control of the heart, including the organization and function of cardiac neurons, the mechanisms of vagal nerve stimulation, and the development of targeted neuromodulation techniques for treating heart failure and arrhythmias. His work involves both basic neuroscience and translational applications, aiming to improve therapeutic strategies for cardiovascular diseases through innovative neuromodulation approaches.

Research topics

• Internal medicine
• Neuroscience
• Medicine
• Psychology
• Biology
• Cardiology
• Anatomy

Selected publications

• BS-534526-002 CHRONIC VAGUS NERVE STIMULATION ATTENUATES SENSORY–SYMPATHETIC ACTIVATION AND INFLAMMATION AFTER MYOCARDIAL INFARCTION

  Heart Rhythm · 2026-04-01

  articleOpen access
  PublisherOA PDFDOI

• Selective vagus nerve stimulation to target cardiac efferent activity in humans for treatment of heart disease

  Physiology · 2025-05-01

  article

  Introduction and Objective: Spatially selective vagus nerve stimulation (sVNS) offers a promising solution to mitigate the off-target effects associated with traditional VNS in which the whole nerve is stimulated. This could serve as a precise method to address chronic heart failure by specifically targeting efferent cardiac fibres and thereby enhance therapeutic outcomes by avoiding off-target effects and eliminating the need for titration. However, the spatial organisation of afferent and efferent cardiac-related fibres within the vagus nerve remains unknown. To address this, we have determined the functional organisation of the cardiac afferent and efferent projections within the cervical vagus nerve of pigs and have initiated translational work in humans. Methods: A multi-electrode sVNS cuff (28-electrode array: 2 rings x 14 electrodes) was placed at the mid-cervical level of the exposed left vagus nerve in pigs and prior to surgical implantation of an FDA approved VNS device in consenting epilepsy patients (NCT05664854, REC 22/LO/0463). Current was applied sequentially to each pair of electrodes in the same radial (o’clock) position on the 2 rings while recording evoked cardiac, pulmonary and laryngeal responses. This was repeated at different parameters optimised for the respective functional responses and repeated after vagotomy in pigs. Results: In pigs, there were 2.0±1.7 (mean±SD) most effective electrode pairs eliciting heart rate (HR) decrease of -7.8±3.4% associated with cardiac efferent activation. A HR increase of 10.2±5.3% (n=6) was induced and sustained post-vagotomy, associated with cardiac afferent activation. There was significant spatial separation of all four regions but specifically, cardiac afferent and efferent CoMs (200±137°, p<0.05, mean±1SD) at the mid-cervical level. In preliminary studies in one human, there was 5% tachycardia with full VNS. During sVNS, this was sustained with 3-4% tachycardia for 11/14 electrode pairs (cardiac afferent). On 3 electrodes, a 4, 5, and 7.5% bradycardia was achieved, respectively. This displayed selective activation of cardiac efferent projections. Conclusions: Significant separation between afferent and efferent cardiac-related regions occurred in all pigs, localised to roughly the opposite sides of the nerve, in close proximity to the pulmonary and laryngeal regions, respectively. For the first time, we have shown this within the vagus nerve in one human; work is in progress on further human studies. This would allow the ability to selectively elicit therapeutic-related efferent effects without affecting afferent-related reflexes. This paves the way for more targeted neuromodulation to enhance precision and efficacy of VNS therapy in treating heart failure. Medical Research Council Grant MR/Z504555/1 National Institutes of Health grant 3OT2OD026545 This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.

  PublisherDOI

• Right stellate ganglion stimulation modulates arrhythmogenesis in acute left lateral ventricular ischemia

  Utrecht University Repository (Utrecht University) · 2025-08-01

  articleOpen access

  Aims Acute myocardial ischaemia causes fatal arrhythmias as result of a flow of 'injury current'. Left stellate ganglion stimulation (LSGS) modulates the injury current and is arrhythmogenic during left anterior ventricular wall ischaemia. The role of right stellate ganglion stimulation (RSGS) in arrhythmogenesis is unclear. We hypothesized that RSGS is proarrhythmic during left lateral ventricular wall ischaemia. Methods and results In 11 anaesthetized female pigs, ventricular repolarization was measured in unipolar epicardial electrograms from the left lateral ventricular wall. Seven subsequent episodes of acute ischaemia (5 min) were produced by occlusion of the circumflex coronary artery (CX), separated by 20 min of reperfusion. The second occlusion served as a control. After 3 min of ischaemia during the third occlusion, LSGS was initiated for 30 s. In the 4th occlusion, RSGS was performed. After decentralization of both left and right stellate ganglia and vagal nerves, LSGS and RSGS were initiated (6th and 7th occlusions). RSGS during ischaemia was more arrhythmogenic than LSGS or control with more spontaneous ventricular premature beats (3-5 min of ischaemia) and two instances of ventricular fibrillation. The LSGS-induced effect on repolarization was absent in myocardium that had been ischaemic for 3 min by CX occlusion. Conclusions LSGS-induced repolarization shortening is absent in ischaemic myocardium. RSGS was more arrhythmogenic following CX occlusion than LSGS or control. These data demonstrate that the arrhythmogenic influence of RSGS or LSGS is contingent on the location of ischaemic zone supporting the clinical findings that bilateral sympathectomy is superior to left sympathectomy alone.

  Publisher

• IS090 ADVANCES IN OUR CLINICAL UNDERSTANDING OF AUTONOMIC REGULATION THERAPY USING VAGAL NERVE STIMULATION IN PATIENTS WITH HEART FAILURE

  Neuromodulation Technology at the Neural Interface · 2025-01-01

  articleOpen access1st authorCorresponding
  PublisherDOI

• Right stellate ganglion stimulation modulates arrhythmogenesis in acute left lateral ventricular ischaemia

  Cardiovascular Research · 2025-07-14 · 1 citations

  articleOpen access

  AIMS: Acute myocardial ischaemia causes fatal arrhythmias as result of a flow of 'injury current'. Left stellate ganglion stimulation (LSGS) modulates the injury current and is arrhythmogenic during left anterior ventricular wall ischaemia. The role of right stellate ganglion stimulation (RSGS) in arrhythmogenesis is unclear. We hypothesized that RSGS is proarrhythmic during left lateral ventricular wall ischaemia. METHODS AND RESULTS: In 11 anaesthetized female pigs, ventricular repolarization was measured in unipolar epicardial electrograms from the left lateral ventricular wall. Seven subsequent episodes of acute ischaemia (5 min) were produced by occlusion of the circumflex coronary artery (CX), separated by 20 min of reperfusion. The second occlusion served as a control. After 3 min of ischaemia during the third occlusion, LSGS was initiated for 30 s. In the 4th occlusion, RSGS was performed. After decentralization of both left and right stellate ganglia and vagal nerves, LSGS and RSGS were initiated (6th and 7th occlusions). RSGS during ischaemia was more arrhythmogenic than LSGS or control with more spontaneous ventricular premature beats (3-5 min of ischaemia) and two instances of ventricular fibrillation. The LSGS-induced effect on repolarization was absent in myocardium that had been ischaemic for 3 min by CX occlusion. CONCLUSIONS: LSGS-induced repolarization shortening is absent in ischaemic myocardium. RSGS was more arrhythmogenic following CX occlusion than LSGS or control. These data demonstrate that the arrhythmogenic influence of RSGS or LSGS is contingent on the location of ischaemic zone supporting the clinical findings that bilateral sympathectomy is superior to left sympathectomy alone.

  PublisherOA PDFDOI

• O002 DECIPHERING THE ANATOMICAL AND FUNCTIONAL ORGANIZATION OF CARDIAC FIBERS IN THE PORCINE CERVICAL VAGUS NERVE FOR SPATIALLY SELECTIVE CARDIAC EFFERENT NEUROMODULATION

  Neuromodulation Technology at the Neural Interface · 2025-01-01

  article
  PublisherDOI

• Neuropeptide Y regulation of L-type Ca ²⁺ channel activity is altered following chronic myocardial infarction

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-11-29

  preprintOpen access

  Abstract Neuropeptide Y (NPY) is a co-transmitter released from sympathetic neurons along with norepinephrine (NE). It has been observed that cardiac NPY levels are significantly elevated following myocardial infarction (MI), and this has been linked to an increase in ventricular arrhythmogenicity associated with elevated sympathetic tone. However, the effects that NPY has on the electrical activity of ventricular myocytes remain poorly understood. Previous studies have examined the influence of NPY alone on cardiac ion channel function, but not in the presence of NE, which is the situation expected in vivo. Furthermore, no one has examined the effects of NPY on ion channel activity following MI. The present study explored the impact of NPY on the L-type Ca 2+ current in ventricular myocytes isolated from the hearts of normal healthy pigs and pigs subjected to MI. We found that NPY alone has a stimulatory effect on the Ca 2+ current in myocytes isolated from healthy pigs. However, in the presence of NE, the effect of NPY was inhibitory. The stimulatory effect of NPY alone was blocked by the Y 1 receptor antagonist BIBO3304, while the inhibitory effect observed in the presence of NE was blocked by the Y 2 receptor antagonist BIIE0246. When the effects of NPY were examined using hearts from pigs following recovery from MI, the stimulatory effect of NPY was absent in myocytes obtained from both remote and border zone areas of infarcted hearts. The inhibitory effect of NPY observed in the presence of NE was also absent in myocytes from remote areas of the infarcted heart. However, the inhibitory effect of NPY observed in the presence of NE was intact in border zone cells. The implications of these results are discussed as they relate to the potential arrhythmogenic effects of NPY following MI. Graphical Abstract. NPY exerts bimodular, context dependent effects on LTCC. Proposed signaling pathways for diverse effects of NPY in ventricular cardiac myocytes. Norepinephrine (NE) and neuropeptide Y (NPY) co-application results in a Y 2 /G i -mediated reduction in β-adrenergic (βAR)/G s enhanced I CaL , while NPY alone modestly enhances the current via Y 1 /G q mechanism. These pathways are regionally altered following chronic MI.

  PublisherOA PDFDOI

• O133 REGULATION OF CARDIAC NEUROTRANSMITTERS BY AXONAL MODULATION

  Neuromodulation Technology at the Neural Interface · 2025-01-01

  articleSenior author
  PublisherDOI

• Noradrenergic and cholinergic innervation of the normal human heart and changes associated with cardiomyopathy

  The Anatomical Record · 2025-05-14 · 2 citations

  articleOpen access

  Autonomic nerves are crucial in cardiac function and pathology. However, data on the distribution of cholinergic and noradrenergic nerves in normal and pathologic human hearts is lacking. Nonfailing donor hearts were pressure-perfusion fixed, imaged, and dissected. Left ventricular cardiomyopathy samples were also obtained. Fixed frozen sections were immunostained for nerves, and adjacent tissue underwent clearing for 3D visualization. Cholinergic and noradrenergic nerves were evenly abundant in both atria, except the sinoatrial node, where vesicular acetylcholine transporter (VAChT) nerves were dominant. Noradrenergic consistently outnumbered cholinergic nerves in right (RV) and left ventricular (LV) regions. Noradrenergic innervation of LV regions varied between donors. Cholinergic innervation was higher in RV compared to LV samples, which generally had reduced VAChT nerves. Marked neural remodeling occurred in three cardiomyopathy cases. Tyrosine hydroxylase (TH) nerve density was increased in the right atrial appendage, and all nerves showed a trend to decrease in the left atrial appendage. Cholinergic innervation was reduced in the LV, and TH innervation was heterogeneous. Noradrenergic nerves were present in granulation tissue but absent in regions of dense scar. Some border zone regions had reduced TH innervation but no hyperinnervation. Dual innervation of most atrial regions supports balanced regulation of atrial function. Higher cholinergic input to the sinoatrial node favors vagal dominance in heart rate regulation. Innervation patterns support a significant role of noradrenergic input to the ventricle, especially on the left. Both atrial and ventricular nerves remodel in cardiomyopathy, providing a foundation for asymmetric neural input and dysregulation of cardiac electromechanical function.

  PublisherDOI

• Comparing the Memory Effects of 50-Hz Low-Frequency and 10-kHz High-Frequency Thoracic Spinal Cord Stimulation on Spinal Neural Network in a Myocardial Infarction Porcine Model

  Neuromodulation Technology at the Neural Interface · 2024-07-31 · 1 citations

  articleOpen access

  OBJECTIVE: This study evaluated the effects of cessation of both conventional low-frequency (50 Hz) and high-frequency (10 kHz) spinal cord stimulation (SCS) on the cardiospinal neural network activity in pigs with myocardial infarction (MI). The objective is to provide an insight into the memory effect of SCS. MATERIALS AND METHODS: In nine Yorkshire pigs, chronic MI was created by delivering microspheres to the left circumflex coronary artery. Five weeks after MI, anesthetized pigs underwent sternotomy to expose the heart for performing acute ischemia intervention, and laminectomy to expose the T1-T4 spinal regions for extracellular in vivo neural recording and SCS. Cardiac ischemic-sensitive neurons were identified by selective responsiveness to left anterior descending (LAD) coronary artery occlusion. SCS episodes were delivered in a random order between low- (50 Hz) and high- (10 kHz) frequency, for 1 minute, at 90% of the motor threshold current. Neural firing and synchrony of ischemic-sensitive spinal neurons were evaluated before vs after SCS. RESULTS: Using a 64-channel microelectrode array, 2711 spinal neurons were recorded extracellularly. LAD ischemia excited 228 neurons that were labeled as ischemic-responsive neurons. The cessation of 50-Hz SCS caused a higher activation than did inhibition of ischemic-responsive neurons (41 activated vs 19 inhibited), whereas the cessation of 10-kHz SCS caused an opposite response with higher inhibition (11 activated vs 28 inhibited, p < 0.01 vs 50 Hz). Termination of low-frequency SCS caused an increase in ischemic-responsive neuronal firing rate compared with high-frequency SCS (50 Hz: 0.39 Hz ± 0.16 Hz, 10 kHz: -0.11 Hz ± 0.057 Hz, p < 0.01). In addition, SCS delivered at 50 Hz increased the number of synchronized pairs of neurons by 205 pairs, whereas high-frequency SCS decreased the number of synchronized pairs by 345 pairs (p < 0.01). CONCLUSIONS: High-frequency (10 kHz) stimulation provides persistent suppression of the ischemia-sensitive neurons after termination of SCS. In contrast, the spinal neural network reverted to excitatory state after termination of low-frequency (50 Hz) stimulation.

  PublisherOA PDFDOI

Recent grants

• NIH Grant R01HL071830

  NIH · $2.8M · 2015

• Bioelectric monitoring and neuromodulation of the heart

  NIH · $3.4M · 2023–2027

• Cardiac Neuromodulation: Mechanisms and Therapeutics

  NIH · $9.1M · 2023–2028

• NIH Grant R01HL058140

  NIH · $1.3M · 2003

• Cardiac Neuromodulation: Mechanisms and Therapeutics

  NIH · $4.5M · 2023–2028

Frequent coauthors

• J. Andrew Armour

  University of Pittsburgh

  122 shared

• Kalyanam Shivkumar

  UCLA Health

  95 shared

• Siamak Salavatian

  University of Pittsburgh

  40 shared

• Olujimi A. Ajijola

  Texas Cardiac Arrhythmia

  36 shared

• Donald B. Hoover

  East Tennessee State University

  35 shared

• E. Marie Southerland

  Environmental Protection Agency

  34 shared

• Éric Beaumont

  East Tennessee State University

  29 shared

• Pradeep S. Rajendran

  28 shared

Education

• PhD, Physiology and Biophysics

  University of Washington

  1980

• B.A.

  Colorado College

  1975

Awards & honors

• Suzanne Eaton, Ph.D. Memorial Prize
• Taylor M. Brown Memorial Award
• Asrican Sophie & Jack Award