Functional and Topographic Concordance of Right Atrial Neural Structures Inducing Sinus Tachycardia

Abstract

Cardiorespiratory autonomic control is in tight interaction with an intracardiac neural network modulating sinus node function. To gain novel mechanistical insights and to investigate possible novel targets concerning the treatment of inadequate sinus tachycardia, we aimed to characterize functionally and topographically the right atrial neural network modulating sinus node function. In 16 sheep 3-dimensional electro-anatomical mapping of the right atrium was performed. In five animals additionally magnetically steered remote navigation was used. Selective stimulation of nerve fibers was conducted by applying high frequency (200 Hz) electrical impulses within the atrial refractory period. Histological analysis of whole heart preparations by acetylcholinesterase staining was performed and compared to the acquired neuroanatomical mapping.We found that neural stimulation in the cranial part of the right atrium, within a perimeter around the sinus node area, elicited predominantly shortening of the sinus cycle length of -20.3 ± 10.1 % (n = 80, P < 0.05). Along the course of the crista terminalis atrial premature beats (n = 117) and atrial fibrillation (n = 123) could be induced. Catheter stability was excellent during remote catheter navigation. Histological work-up (n = 4) was in accord with the distribution of neurostimulation sites. Ganglions were mainly innervated by the dorsal right-atrial subplexus, with substantial additional input from the ventral right atrial subplexus. In conclusion, our findings suggest a functional and topographic concordance of right atrial neural structures inducing sinus tachycardia. This might open up new avenues in the treatment of heart rate related disorders.

Disruption of cardiac cholinergic neurons enhances susceptibility to ventricular arrhythmias

“…Whole-mount immunostainings were performed in intact murine hearts to examine the interconnectivity of atrial and ventricular neural structures within the intracardiac neural network and cholinergic ventricular innervation 55 . Neurofilament staining (chicken anti NF-H, 1:3,000; EMD Millipore) was used to characterize the intracardiac neural network traversing along the pulmonary veins, the posterior left atrium and both ventricles.…”

“…Neurofilament staining (chicken anti NF-H, 1:3,000; EMD Millipore) was used to characterize the intracardiac neural network traversing along the pulmonary veins, the posterior left atrium and both ventricles. We used fluorescent and chromogenic labelling for TH and ChAT (goat α ChAT, 1:50; EMD Millipore; rabbit α TH, 1:1,000; EMD Millipore) to characterize adrenergic and cholinergic structures 35 55 56 . Male ChAT BAC -eGFP transgenic mice were purchased from Jackson Laboratories (Bar Harbor, ME, USA; stock number 007902; ref.…”

Wearable Sensors in Syncope Management

“…During the development of NMS, postural-dependant venous blood pooling sets off a cascade of autonomic reflexes [ 9 , 10 ]. The resulting neurally-mediated hemodynamic adaptations [ 11 , 12 ] typically result in a decline in blood pressure (BP) and a change (decrease or increase) in heart rate (HR) [ 13 ]. Hemodynamic studies indicate that vasodilatation is the most common reproducible phenomenon occurring just prior to the onset of dizziness or a sudden loss of consciousness [ 2 , 14 ].…”

Development of nonfibrotic left ventricular hypertrophy in an ANG II-induced chronic ovine hypertension model

“…Cardiovascular magnetic resonance (CMR) imaging is currently the accepted reference method for noninvasive quantification of cardiac volumes, mass, and function (Bellenger et al 2000;Hundley et al 2010) and is increasingly used in large animal models (Tschabrunn et al 2015). Sheep are widely employed as animal models for the human cardiovascular system, as they possess an electrical and hemodynamical physiology similar to humans (Meyer et al 2010;Dardenne et al 2013;Eickholt et al 2013). ANG II treatment is well established in small animals (Charles et al 1995;Stevens and Lumbers 1999), but effects over several weeks regarding cardiac function and remodeling in sheep remain unknown.…”