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

Abstract

Sympathetic control of regional cardiac function occurs through post-ganglionic innervation from stellate ganglia and thoracic sympathetic chain. While norepinephrine (NE) is their primary neurotransmitter, neuropeptide Y (NPY) is an abundant cardiac co-transmitter. 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, multi-channel 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 intra-operative determination of cardiac neuropeptides and deployment as a minimally invasive catheter.

Development of an Electrochemical, Aptamer-Based Sensor for Dynamic Detection of Neuropeptide Y

“…Any entity that nonspecifically adsorbs to an electrode surface will cause changes , that can result in signal convolution. Another revealing example of NPY sensing is provided in a report by Kluge et al, who described the production of a capacitive immunoprobe for NPY. They specifically designed the probe to measure NPY concentrations in cardiac events.…”

Tiered sympathetic control of cardiac function revealed by viral tracing and single cell transcriptome profiling

“…Furthermore, the importance of NPY as a cardiac neurotransmitter is underscored by the recent finding that cardiac sympathetic blockade using beta-adrenergic receptor antagonists without NPY antagonists did not significantly raise ventricular fibrillation threshold, however, concomitant antagonism of both NPY and beta-receptor signaling did ( Kalla et al, 2020 ). Additionally, low frequency sympathetic ganglion stimulation induced cardiac norepinephrine release, however, high frequency stimulation induced norepinephrine and NPY release into the myocardium from distal axonal projections from sympathetic neurons ( Kluge et al, 2021 ). These data, interpreted in light of the new findings in this study, suggest that cardiac sympathetic regulation exists as a two-tiered system, where low-level cardiac sympathoexcitation is mediated by NPY-low or NPY-negative neurons, whereas high-level sympathoexcitation requires the recruitment of NPY expressing neurons.…”

Effects of Massage on Neuro-Vascular Regulation and Apoptosis in Rabbits with Cervical Spondylosis of the Vertebral Artery Type

“…NPY is a co-transmitter released from the postsympathetic ganglia, especially at higher levels of sympathetic excitation [24]. Elevated sympathetic stress leads to increased NPY and NE release [25]. NPY and NE have a synergistic effect, jointly regulating vascular tone and potentiating NE-mediated vasoconstriction [26].…”