Kalyanam Shivkumar
University of California-Los Angeles, CA·Medicine & Clinical Research
The heart does not beat on its own schedule alone. Nerves of the autonomic nervous system, the involuntary control system that speeds the heart under stress and slows it at rest, continually tune its electrical behavior.
- Fields
Medicine & Clinical Research
Physiology
Biomedical Engineering
- Topics
neurocardiology
autonomic nervous system
sympathetic nervous system
- Grants
- 3 known grants, through Jul 2028
What they work on
- Define the ultrastructure of cardiac nerves and the nerve-to-myocyte ratio in normal and chronically infarcted hearts, using tissue clearing for three-dimensional imaging in a large animal model and in human hearts.
- Measure neurotransmitter and neuropeptide release in the heart muscle during physiological stressors and locate regions where release is non-uniform, to test whether scars cause patchy chemical signaling that triggers ventricular arrhythmias.
- Determine the mechanism and potential benefit of vagal nerve stimulation in limiting pathological remodeling of scar tissue and its nerve supply after myocardial infarction.
- Correlate regional electrical behavior from high-density three-dimensional cardiac mapping with real-time in vivo neurotransmitter detection across the scar border zone in beating infarcted hearts.
- Develop bioelectronic interfaces for real-time measurement of cardiac and vascular neurotransmitters, combining electrochemical cyclic voltammetry for catecholamines with capacitive immunoprobes for neuropeptides.
- Map electrical heterogeneities across the ischemic heart's border zone using intramyocardial multipole electrodes and thin-film two-dimensional microarrays applied to the epicardium.
- Implement multi-input, multi-output closed-loop neuromodulation, in which continuous measurements of cardiac electrical and neurochemical status automatically adjust autonomic stimulation.
More about the research
After a heart attack leaves a scar, nerves around that scar grow back abnormally. Dangerous rhythm disturbances of the lower chambers (ventricular arrhythmias) and sudden cardiac death often follow. A common thread across these projects is a single idea, the Spatiotemporal Heterogeneity of Neurotransmitter Release Hypothesis: scars distort the fine structure of cardiac nerves so that chemical signals are released unevenly across the heart muscle, and that patchiness is a direct trigger for lethal arrhythmias. The work combines detailed electrical mapping of the heart, real-time chemical sensing at nerve endings, three-dimensional tissue imaging, and nerve stimulation as a therapy.
Why it matters
Sudden cardiac death after a heart attack and heart failure are among the most common causes of death in the United States, and existing monitors reveal little about how nerves are acting on the heart in real time. Mapping where nerve signaling becomes uneven around scar tissue could identify patients at high risk and show why vagal nerve stimulation helps. The sensing and closed-loop neuromodulation technology could eventually support targeted autonomic therapy during cardiac surgery, after operations and in critical care.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Thomas Everett
Indiana University-Purdue University-Indianapolis, IN·Medicine & Clinical Research
Test whether skin sympathetic nerve activity (SKNA), nerve signals recorded noninvasively from the skin, predicts brain recovery in cardiac arrest patients receiving targeted temperature management, a protective cooling therapy.
Qandeel Soomro
New York University, NY·Medicine & Clinical Research·Early-career
Deeply profile autonomic nervous system dysfunction across stages of chronic kidney disease using a comprehensive battery of autonomic tests, both cross-sectionally and over time, to test whether dysfunction shifts from parasympathetic to sympathetic as CKD advances.
Peter Hanna
University of California-Los Angeles, CA·Medicine & Clinical Research·Early-career
Identify which ganglionated plexus neurons supply the pulmonary veins and back wall of the left atrium by injecting a retrograde neural tracer into donated human hearts and imaging them with confocal microscopy.
The school
University of California-Los Angeles: 84 labs on PI Pages, $1.9B a year on research, 803 research doctorates a year.
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