Cardiac sympathetic innervation, from a different point of (re)view

Abstract

The audience of basic and clinical scientists is familiar with the notion that the sympathetic nervous system controls heart function during stresses. However, evidence indicates that the neurogenic control of the heart spans from the maintenance of housekeeping functions in resting conditions to the recruitment of maximal performance, in the fight-or-flight responses, across a whole range of intermediate states. To perform such sophisticated functions, sympathetic ganglia integrate both peripheral and central inputs, and transmit information to the heart via 'motor' neurons, directly interacting with target cardiomyocytes. To date, the dynamics and mode of communication between these two cell types, which determine how neuronal information is adequately translated into the wide spectrum of cardiac responses, are still blurry. By combining the anatomical and structural information brought to light by recent imaging technologies and the functional evidence in cellular systems, we focus on the interface between neurons and cardiomyocytes, and advocate the existence of a specific 'neuro-cardiac junction', where sympathetic neurotransmission occurs in a 'quasi-synaptic' way. The properties of such junctional-type communication fit well with those of the physiological responses elicited by the cardiac sympathetic nervous system, and explain its ability to tune heart function with precision, specificity and elevated temporal resolution.

Circadian‐timed quick‐release bromocriptine lowers elevated resting heart rate in patients with type 2 diabetes mellitus

“…Such a SNS target of B‐QR would be consistent with the reported sympatholytic mechanism of action of circadian‐timed B‐QR therapy to improve glycaemic control and reduce CVD risk in type 2 diabetes subjects . However, although SNS innervation of the myocardium is extensive and exerts a prominent control of myocardial function, reduced parasympathetic drive to the heart may also contribute to elevated RHR and central dopamine action can function to reverse this vagal imbalance as well, an effect which may also participate in the observed B‐QR effects on elevated RHR in this study.…”

“…An understanding of why the magnitude of the B‐QR effect to reduce RHR predicts the magnitude of its effect to reduce HbA1c in type 2 diabetes subjects whose glycemia is poorly controlled may best be obtained by (a) appreciating the relationship between RHR and SNS tone on the one hand and the influence of chronic elevated SNS activity upon cardiometabolic health and glycaemic control on the other and (b) realizing the sympatholytic nature of circadian B‐QR therapy upon chronically elevated SNS tone in insulin‐resistant states as follows. Importantly, in insulin resistance syndrome, elevated RHR (over 70‐80 BPM) is a marker of an increase in cardiac SNS dominance either in absolute terms or in relative terms of SNS/parasympathetic nervous system (PSNS) activity balance and SNS overactivity is considered to be the most likely central mechanism to explain the association between elevated RHR and adverse cardiometabolic outcomes . While the autonomic imbalance of elevated SNS and depressed PSNS activities to the heart each can contribute to elevated RHR, available evidence suggests that the elevated RHR association with insulin resistance syndrome is most closely coupled to overactive SNS tone that involves several metabolic tissues in addition to the heart .…”

Dynamics of neuroeffector coupling at cardiac sympathetic synapses

“…In summary, our in vivo data, showing the spatial selectivity of SN activation of SAN responses, the functional evidence of elevated [NE] cleft , and the kinetics of neuroeffector coupling, are all in support of the working model where the establishment of a specialized extracellular domain enables sympathetic neurotransmission to the heart to occur in a quasi‐synaptic fashion (Zaglia & Mongillo, ).…”

Reduced left ventricular filling following blood volume extraction does not result in compensatory augmentation of cardiac mechanics

“…In contrast, during LBNP at −60 mmHg, suggested to be equivalent to 25% of total blood volume loss (Johnson et al., ), a significant increase in HR (Hodt et al., , ; Williams et al., ) and SNA was evident (Johnson et al., ; Rickards et al., ) and accompanied by a marked increase in LV twist mechanics. This suggests that there might be a threshold at which increased SNA augments LV twist (Zaglia & Mongillo, ), and that the relatively slow withdrawal of blood, even to the point of presyncope, does not exceed this threshold. Further work examining rapid blood volume extraction, potentially a better model of haemorrhage, might invoke a greater SNA response and thereby augment LV twist mechanics.…”