Research
Our Mission
Our laboratory’s mission is to understand the autonomic nervous system’s control of the heart in health and disease and determine its role in contributing to arrhythmias and heart failure. Our prior studies have evaluated the role of sympathoexcitation and parasympathetic dysfunction in cardiovascular diseases. We have ongoing studies on several aspects of the autonomic neuraxis from the heart and its receptors to the thoracic and extra-thoracic neuraxis.
About Cardiovascular Disease
Cardiovascular disease is an important cause of morbidity and mortality in the U.S. and worldwide. Nearly all cardiovascular diseases are associated with cardiac autonomic nervous system dysfunction, which can initiate and cause further exacerbation of heart disease. Many successful therapies for arrhythmias and heart failure have, in fact, targeted the cardiac autonomic nervous system.
Pictured: Immunofluorescence and confocal microscopy reveals respiratory neurons in green and cardiac neurons in red.
Neurocardiac Interactions
The heart is innervated by the sympathetic and parasympathetic branches of the nervous system. In normal hearts, these branches of the nervous system exist in a healthy balance to coordinate cardiovascular function on a beat-to-beat basis and to modulate cardiovascular parameters based on the needs of the body. In the setting of cardiovascular disease, however, this autonomic balance undergoes pathological remodeling, characterized by sympathetic hyperactivity and parasympathetic withdrawal. Such autonomic imbalance can predispose to ventricular arrhythmias, progression of heart failure, and increased risk of sudden cardiac death.
Additional images depict:
- Mechanisms of neurocardiac interactions. The sympathetic and parasympathetic branches of the autonomic nervous system relay information either to the brain or directly back to the heart via intrinsic cardiac pathways, intrathoracic pathways, or centrally projecting pathways. These same pathways alter cardiac function by releasing neurotransmitters directly onto the heart.
- Sympathetic and parasympathetic neurons release neurotransmitters which bind to receptors on the heart to modulate various cardiovascular parameters, including heart rate, blood pressure, contractility, and speed of electrical conduction.
- Scar formation induced by myocardial infarction or other cardiovascular disease results in heterogenous innervation of scar and border-zone regions, which predisposes to ventricular arrhythmias.
Techniques and Projects
We use advanced techniques such as viral tracing and optogenetics in mice to better understand cardiac innervation. Our laboratory has several ongoing studies on identifying the molecular markers of different subpopulations of cardiac neurons and support cells and examining how changes in these cells can contribute to arrhythmogenesis. By using optogenetics to activate specific neuronal pathways, we gain insight into the functional role of specific neuronal subpopulations in health and disease.
Leveraging these mechanistic insights, we can refine their pathophysiological role in a translational large animal model. These large animal studies allow us to evaluate the efficacy of various neuromodulatory therapies on diseased hearts using high-resolution electroanatomic mapping and electrophysiological recordings.
Finally, in our human studies, we work directly with heart disease patients to study the anti-arrhythmic effects of neuromodulatory approaches such as vagal nerve stimulation. Ultimately, the mission of our research is to translate our findings from the bench to the bedside, improving the lives of the millions of patients that live with heart disease.
Additional Graphics
Pictured: Polar maps are spatial depictions of the duration of cardiac action potentials across both ventricles of the heart. In response to pathological changes caused by cardiovascular disease, as well as various interventions including drug administration and nerve stimulation, differences in action potential duration across the heart can be observed.
Pictured: MRI images of an infarcted heart display transverse cross-sections of each of the heart's chambers and an anteroseptal scar.