Sudden cardiac death (SCD) due to ventricular arrhythmias is the leading cause of mortality in the United States, resulting in 250,000 deaths/year. The autonomic nervous system plays a major role in the pathophysiology of arrhythmias leading to SCD and neuraxial modulation provides an important venue for therapeutic intervention. The major goal of our research is to investigate the role of cardiac sympathetic innervations in the genesis of arrhythmias, and that of neuraxial modulation in prevention of these arrhythmias in humans. The mechanisms underlying sympathetic control of myocardial excitability in normal and diseased human hearts, and specifically, regional differences (apex versus base, epicardium versus endocardium, right versus left stellate ganglion innervation) remain unknown and need to be studied. Further, myocardial scars seen in ischemic and non-ischemic cardiomyopathy show nerve sprouting at the border zone of scars due to neural remodeling, which has been implicated in the pathophysiology of ventricular arrhythmias. The functional effects of nerve stimulation in this setting and how neuraxial blockade works in humans in these diseases are still unknown and this knowledge can help guide therapy. In this proposal, electrophysiological effects of direct regional cardiac nerve stimulation and neuraxial modulation of the thoracic sympathetic ganglia will be investigated. Areas of the heart regulated by the right and left stellate ganglia will be delineated in patients undergoing interventional electrophysiology procedures and cardiac transplantation. Understanding neuraxial modulation has the potential to further develop therapies that target these pathways in the very near term. Therapies such as right, left, or bilateral cerviocothoracic sympathectomy which has been 're-introduced'into clinical practice (by our group and others) already show a lot of promise and could emerge as novel/elegant therapies that are also cost-effective for the prevention of SCD. Therefore, neuraxial modulation is an approach that has the potential to have a global impact given the prohibitive high cost and morbidity associated with implantable defibrillators which prevent their expanded use.

Public Health Relevance

The project seeks to identify the pathways that regulate sympathetic output to the heart and study its modulation and role in ventricular arrhythmias. Ventricular tachycardia and fibrillation are thought to be the major cause of sudden cardiac death resulting in over 250,000 deaths/year in the USA. By defining the regulation of these nerves in humans we can improve the treatment of these arrhythmias and prevent sudden cardiac death.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
Project #
Application #
Study Section
Special Emphasis Panel (ZRG1-CVRS-E (02))
Program Officer
Lathrop, David A
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of California Los Angeles
Internal Medicine/Medicine
Schools of Medicine
Los Angeles
United States
Zip Code
Nakamura, Keijiro; Ajijola, Olujimi A; Aliotta, Eric et al. (2016) Pathological effects of chronic myocardial infarction on peripheral neurons mediating cardiac neurotransmission. Auton Neurosci 197:34-40
Teng, Alexandra E; Lustgarten, Daniel L; Vijayaraman, Pugazhendhi et al. (2016) Usefulness of His Bundle Pacing to Achieve Electrical Resynchronization in Patients With Complete Left Bundle Branch Block and the Relation Between Native QRS Axis, Duration, and Normalization. Am J Cardiol 118:527-34
Rao, Hygriv B; Yu, Ricky; Chitnis, Nishad et al. (2016) Ventricular Tachycardia Ablation in the Presence of Left Ventricular Thrombus: Safety and Efficacy. J Cardiovasc Electrophysiol 27:453-9
Shivkumar, Kalyanam; Ajijola, Olujimi A; Anand, Inder et al. (2016) Clinical neurocardiology defining the value of neuroscience-based cardiovascular therapeutics. J Physiol 594:3911-54
Rajendran, Pradeep S; Nakamura, Keijiro; Ajijola, Olujimi A et al. (2016) Myocardial infarction induces structural and functional remodelling of the intrinsic cardiac nervous system. J Physiol 594:321-41
Watanabe, Atsuyuki; Seki, Atsuko; Fishbein, Michael C et al. (2016) Arrhythmogenic Right Ventricular Cardiomyopathy: Electroarchitecture of the Substrate. HeartRhythm Case Rep 2:47-51
Buckley, Una; Yamakawa, Kentaro; Takamiya, Tatsuo et al. (2016) Targeted stellate decentralization: Implications for sympathetic control of ventricular electrophysiology. Heart Rhythm 13:282-8
Rashid, Shams; Rapacchi, Stanislas; Shivkumar, Kalyanam et al. (2016) Modified wideband three-dimensional late gadolinium enhancement MRI for patients with implantable cardiac devices. Magn Reson Med 75:572-84
Buckley, Una; Shivkumar, Kalyanam (2016) Stress-induced cardiac arrhythmias: The heart-brain interaction. Trends Cardiovasc Med 26:78-80
Buch, Eric; Share, Michael; Tung, Roderick et al. (2016) Long-term clinical outcomes of focal impulse and rotor modulation for treatment of atrial fibrillation: A multicenter experience. Heart Rhythm 13:636-41

Showing the most recent 10 out of 141 publications