Evaluating intrinsic cardiac neural control of cardiac function using sequential ganglionated plexus ablations v1 (protocols.io.bvpbn5in)

AbstractCardiac function is under exquisite intrinsic cardiac neural control. Neuroablative techniques to modulate control of cardiac function are currently being studied in patients, albeit with variable and sometimes deleterious results. Recognizing the major gaps in our understanding of cardiac neural control, we sought to evaluate neural regulation of impulse initiation in the sinoatrial node as an initial discovery step. Here, we report an in-depth, multi-scale structural and functional characterization of the innervation of the sinoatrial node (SAN) by the right atrial ganglionated plexus (RAGP) in porcine and human hearts. Combining intersectional strategies including tissue clearing, immunohistochemical and ultrastructural techniques, we have delineated a comprehensive neuroanatomic atlas of the RAGP-SAN complex. The RAGP shows significant phenotypic diversity of neurons while maintaining predominant cholinergic innervation. Cellular and tissue-level electrophysiologic mapping and ablation studies demonstrate interconnected ganglia with synaptic convergence within the RAGP to modulate SAN automaticity, atrioventricular (AV) conduction and left ventricular (LV) contractility. For the first time, we demonstrate that intrinsic cardiac neurons influence the pacemaking site in the heart. This provides an experimental demonstration of a discrete neuronal population controlling a specific geographic region of the heart (SAN) that can serve as a framework for further exploration of other parts of the intrinsic cardiac nervous system (ICNS) in mammalian hearts and for developing targeted therapies.

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Metrics of High Cofluctuation and Entropy to Describe Control of Cardiac Function in the Stellate Ganglion

10.1101/2021.09.28.462183 ◽

2021 ◽

Author(s):

Nil Z Gurel ◽

Koustubh B Sudarshan ◽

Joseph Hadaya ◽

Alex Karavos ◽

Taro Temma ◽

...

Keyword(s):

Heart Failure ◽

Cardiac Function ◽

Neural Control ◽

Stellate Ganglion ◽

High Amplitude ◽

Network Activity ◽

Neuronal Populations ◽

Cardiac Control ◽

Blood Pressure Waveform

Neural control of the heart involves dynamic adaptation of mechanical and electrical indices to meet blood flow demands. The control system receives centrally-derived inputs to coordinate cardiac function on a beat-by-beat basis, producing 'functional' outputs such as the blood pressure waveform. Bilateral stellate ganglia (SG) are responsible for integration of multiple inputs and efferent cardiopulmonary sympathetic neurotransmission. In this work, we investigate network processing of cardiopulmonary transduction by SG neuronal populations in porcine with chronic pacing-induced heart failure and control subjects. We derive novel metrics to describe control of cardiac function by the SG during baseline and stressed states from in vivo extracellular microelectrode recordings. Network-level spatiotemporal dynamic signatures are found by quantifying state changes in coactive neuronal populations (i.e., cofluctuations). Differences in 'neural specificity' of SG network activity to specific phases of the cardiac cycle are studied using entropy estimation. Fundamental differences in information processing and cardiac control are evident in chronic heart failure where the SG exhibits: i) short-lived, high amplitude cofluctuations in baseline states, ii) greater variation in neural specificity to cardiac cycles, iii) limited sympathetic reserve during stressed states, and iv) neural network activity and cardiac control linkage that depends on disease state and cofluctuation magnitude. These findings indicate that spatiotemporal dynamics of stellate ganglion neuronal populations are altered in heart failure, and lay the groundwork for understanding dysfunction neuronal signaling reflective of cardiac sympathoexcitation.

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Ten-year follow-up of cardiac function and neural regulation in a group of amateur half-marathon runners

Open Heart ◽

10.1136/openhrt-2020-001561 ◽

2021 ◽

Vol 8 (1) ◽

pp. e001561

Author(s):

Beatrice De Maria ◽

Mariana de Oliveira Gois ◽

Aparecida Maria Catai ◽

Christian Marra ◽

Daniela Lucini ◽

...

Keyword(s):

Cardiovascular Disease ◽

Cardiovascular Risk ◽

Cardiovascular Diseases ◽

Physical Exercise ◽

Cardiac Function ◽

Physical Training ◽

Neural Control ◽

Marathon Runners ◽

Arterial Blood

ObjectiveIn the last years, a debate exists about type, intensity and frequency of physical exercise that is really indicated to protect healthy subjects from cardiovascular disease. Regular physical training has been associated with an improved cardiovascular risk profile, but it has also been demonstrated that strenuous and uncontrolled physical exercise could be dangerous, in terms of increased cardiovascular morbidity and mortality. In the present study, we evaluated a group of 35 amateur half-marathon runners, who were likewise studied 10 years before (B). The results of B suggested that an increased cardiac sympathetic modulation could potentially represent a negative prognostic factor. The aim of this follow-up was to assess the medium–long-term effects of moderate to vigorous physical training on the cardiovascular neural control, cardiac function and occurrence of cardiovascular diseases.MethodsEach enrolled subject underwent: (1) an interview and physical examination to ascertain the presence of cardiovascular disease; (2) standing test to evaluate the cardiovascular neural control by means of heart rate variability (HRV), arterial blood pressure (AP) variability and baroreflex sensitivity (BRS); (3) transthoracic echocardiography to evaluate cardiac function.ResultsAt 10-year follow-up (FU), in this group of middle-aged athletes the occurrence of cardiovascular diseases was low, not unlike that of the overall population. The results of HRV analysis showed a decreased sympathetic and increased vagal modulation directed to the heart, compared with B. In addition, HRV, AP variability and BRS indices showed a physiological response to active standing. Finally, athletes had normal echocardiographic measures.ConclusionWe conclude that in our group of athletes a regular moderate–vigorous physical training through the 10 years was quite beneficial as the prevalence of sympathetic cardiac modulation observed at B was not accompanied by increased cardiovascular risk, on the contrary a slight prevalence of vagal indices was observed at FU.

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Autonomic Neural Control of Cardiac Function: Modulation by Adenosine and Adenosine 5′-Triphosphate

The American Journal of Cardiology ◽

10.1016/s0002-9149(9x)00257-5 ◽

1997 ◽

Vol 79 (12) ◽

pp. 11-14 ◽

Cited By ~ 27

Author(s):

Amir Pelleg ◽

Guennadi Katchanov ◽

Jiang Xu

Keyword(s):

Cardiac Function ◽

Neural Control

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Innervation and Neuronal Control of the Mammalian Sinoatrial Node a Comprehensive Atlas

Circulation Research ◽

10.1161/circresaha.120.318458 ◽

2021 ◽

Vol 128 (9) ◽

pp. 1279-1296

Author(s):

Peter Hanna ◽

Michael J. Dacey ◽

Jaclyn Brennan ◽

Alison Moss ◽

Shaina Robbins ◽

...

Keyword(s):

Cardiac Function ◽

Neural Control ◽

Sinoatrial Node ◽

Phenotypic Diversity ◽

Functional Characterization ◽

Geographic Region ◽

Left Ventricular ◽

Cholinergic Innervation ◽

Right Atrial ◽

Ventricular Contractility

Rationale: Cardiac function is under exquisite intrinsic cardiac neural control. Neuroablative techniques to modulate control of cardiac function are currently being studied in patients, albeit with variable and sometimes deleterious results. Objective: Recognizing the major gaps in our understanding of cardiac neural control, we sought to evaluate neural regulation of impulse initiation in the sinoatrial node (SAN) as an initial discovery step. Methods and Results: We report an in-depth, multiscale structural and functional characterization of the innervation of the SAN by the right atrial ganglionated plexus (RAGP) in porcine and human hearts. Combining intersectional strategies, including tissue clearing, immunohistochemical, and ultrastructural techniques, we have delineated a comprehensive neuroanatomic atlas of the RAGP-SAN complex. The RAGP shows significant phenotypic diversity of neurons while maintaining predominant cholinergic innervation. Cellular and tissue-level electrophysiological mapping and ablation studies demonstrate interconnected ganglia with synaptic convergence within the RAGP to modulate SAN automaticity, atrioventricular conduction, and left ventricular contractility. Using this approach, we comprehensively demonstrate that intrinsic cardiac neurons influence the pacemaking site in the heart. Conclusions: This report provides an experimental demonstration of a discrete neuronal population controlling a specific geographic region of the heart (SAN) that can serve as a framework for further exploration of other parts of the intrinsic cardiac nervous system (ICNS) in mammalian hearts and for developing targeted therapies.

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