Rapid measurement of cardiac neuropeptide dynamics by capacitive immunoprobe in the porcine heart

Sympathetic control of regional cardiac function occurs through postganglionic innervation from stellate ganglia and thoracic sympathetic chain. Whereas norepinephrine (NE) is their primary neurotransmitter, neuropeptide Y (NPY) is an abundant cardiac cotransmitter. NPY plays a vital role in homeost...

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Bibliographic Details
Published in:American journal of physiology. Heart and circulatory physiology 2021-01, Vol.320 (1), p.H66-H76
Main Authors: Kluge, Nicholas, Dacey, Michael, Hadaya, Joseph, Shivkumar, Kalyanam, Chan, Shyue-An, Ardell, Jeffrey L, Smith, Corey
Format: Article
Language:English
Subjects:
Angiogenesis
Animals
Autonomic nervous system
Cardiac function
Cardiac Pacing, Artificial
Catheters
Congestive heart failure
Electric Stimulation
Electrochemical Techniques
Enzyme-linked immunosorbent assay
Ganglia
Heart
Heart - innervation
Hemodynamic responses
High performance liquid chromatography
Hypertension
In vivo methods and tests
Innervation
Innovative Methodology
Intestine
Liquid chromatography
Male
Mass spectrometry
Mass spectroscopy
Medical instruments
Microdialysis
Myocardial infarction
Myocardium
Myocardium - metabolism
Neuropeptide Y
Neuropeptide Y - metabolism
Neuropeptides
Neurotransmitters
Norepinephrine
Norepinephrine - metabolism
Pathogenesis
Signal Processing, Computer-Assisted
Stellate ganglion
Stimulation
Sus scrofa
Sympathetic nervous system
Sympathetic Nervous System - physiology
Temporal resolution
Time Factors
Vasoactive agents
Vasoactive intestinal peptide
Vasoconstriction
Ventricle
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Summary:Sympathetic control of regional cardiac function occurs through postganglionic innervation from stellate ganglia and thoracic sympathetic chain. Whereas norepinephrine (NE) is their primary neurotransmitter, neuropeptide Y (NPY) is an abundant cardiac cotransmitter. NPY plays a vital role in homeostatic processes including angiogenesis, vasoconstriction, and cardiac remodeling. Elevated sympathetic stress, resulting in increased NE and NPY release, has been implicated in the pathogenesis of several cardiovascular disorders including hypertension, myocardial infarction, heart failure, and arrhythmias, which may result in sudden cardiac death. Current methods for the detection of NPY in myocardium are limited in their spatial and temporal resolution and take days to weeks to provide results [e.g., interstitial microdialysis with subsequent analysis by enzyme-linked immunosorbent assay (ELISA), high performance liquid chromatography (HPLC), or mass spectrometry]. In this study, we report a novel approach for measurement of interstitial and intravascular NPY using a minimally invasive capacitive immunoprobe (C.I. probe). The first high-spatial and temporal resolution, multichannel measurements of NPY release in vivo are provided in both myocardium and transcardiac vascular space in a beating porcine heart. We provide NPY responses evoked by sympathetic stimulation and ectopic ventricular pacing and compare these to NE release and hemodynamic responses. We extend this approach to measure both NPY and vasoactive intestinal peptide (VIP) and show differential release profiles under sympathetic stimulation. Our data demonstrate rapid and local changes in neurotransmitter profiles in response to sympathetic cardiac stressors. Future implementations include real-time intraoperative determination of cardiac neuropeptides and deployment as a minimally invasive catheter. The sympathetic nervous system regulates cardiac function through release of neurotransmitters and neuropeptides within the myocardium. Neuropeptide Y (NPY) acts as an acute cardiac vasoconstrictor and chronically to regulate angiogenesis and cardiac remodeling. Current methodologies for the measure of NPY are not capable of providing rapid readouts on a single-sample basis. Here we provide the first in vivo methodology to report dynamic, localized NPY levels within both myocardium and vascular compartments in a beating heart.
ISSN:0363-6135
1522-1539
DOI:10.1152/AJPHEART.00674.2020