Spatially divergent cardiac responses to nicotinic stimulation of ganglionated plexus neurons in the canine heart

Cardinal, René; Pagé, Pierre; Vermeulen, Michel; Ardell, Jeffrey L.; Armour, J. Andrew

doi:10.1016/j.autneu.2008.11.007

Cited by 64 publications

(66 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These data are in accord with studies using nicotine (Cardinal et al . 2009) or direct electrical stimulation (Butler et al . 1990) of hearts in situ in the dog.…”

Section: Physiology Of the Heart's ‘Little Brain’mentioning

confidence: 99%

The heart's ‘little brain’ controlling cardiac function in the rabbit

Brack

2014

Experimental Physiology

View full text Add to dashboard Cite

New Findings•What is the topic of this review?The topic of the review is the intrinsic cardiac nervous system in the rabbit.•What advances does it highlight?The anatomy of rabbit intrinsic ganglia is similar to that of other species, including humans. Immunohistochemistry confirms the presence of cholinergic and adrenergic neurones, with a striking arrangement of neuronal nitric oxide synthase-positive cell bodies. Activation of atrial ganglia produces effects on local and remote regions.Heart disease is a primary cause of mortality in the developed world, and it is well recognized that neural mechanisms play an important role in many cardiac pathologies. The role of extrinsic autonomic nerves has traditionally attracted the most attention. However, there is a rich intrinsic innervation of the heart, including numerous cardiac ganglia (ganglionic plexuses), that has the potential to affect cardiac function independently as well as to influence the actions of the extrinsic nerves. To investigate this, an isolated, perfused, innervated rabbit Langendorff heart preparation was considered the best option. Although ganglionic plexuses have been well described for several species, there was no full description of the anatomy and histochemistry of rabbit hearts. To this end, rabbit intrinsic ganglia were located using acetylcholinesterase histology (n = 33 hearts). This revealed six generalized ganglionic regions, defined as a left neuronal complex above the left pulmonary vein, a right neuronal complex around the base of right cranial vein, three scattered in the dorsal right atrium and a region containing numerous ventricular ganglia located on the conus arteriosus. Using immunohistochemistry, neurons were found to contain choline acetyltransferase or tyrosine hydroxylase and/or neuronal nitric oxide synthase in differing amounts (choline acetyltransferase > tyrosine hydroxylase > neuronal nitric oxide synthase). The function of rabbit intrinsic ganglia was investigated using a bolus application of nicotine or electrical stimulation at each of the above sites whilst measuring heart rate and atrioventricular conduction. Nicotine applied to different ganglionic plexuses caused a bradycardia, a tachycardia or a mixture of the two, with the right atrial plexus producing the largest chronotropic responses. Electrical stimulation at these sites induced only a bradycardia. Atrioventricular conduction was modestly changed by nicotine, the main response being a prolongation. Electrical stimulation produced significant prolongation of atrioventricular conduction, particularly when the right neuronal complex was stimulated. These studies show that the intrinsic plexuses of the heart are important and could be crucial for understanding impairments of cardiac function. Additionally, they provide a strong basis from which to progress using the isolated, innervated rabbit heart preparation.

show abstract

“…These data are in accord with studies using nicotine (Cardinal et al . 2009) or direct electrical stimulation (Butler et al . 1990) of hearts in situ in the dog.…”

Section: Physiology Of the Heart's ‘Little Brain’mentioning

confidence: 99%

The heart's ‘little brain’ controlling cardiac function in the rabbit

Brack

2014

Experimental Physiology

View full text Add to dashboard Cite

show abstract

“…That neurally induced changes were identified well beyond the tachyarrhythmia sites of origin identified in the Bachmann bundle could be explained by (1) their association with either left, middle, or right dorsal mediastinal nerve stimulation, (2) spatially divergent interconnections within the intrinsic cardiac nervous system, 40,41 and/or (3) the fact that the Bachmann bundle acts as a pathway for rapid conduction between the RA and LA 42,43 and that therefore tachyarrhythmia sites of origin identified in the Bachmann bundle could represent either a local event or an early epicardial breakthrough from relatively distant endocardial sites of origin that would have been missed with the relatively limited resolution of our multielectrode arrays.…”

Section: Relation To Neural Influences On the Atriamentioning

confidence: 99%

Atrial Tachyarrhythmias and Repolarization Changes Induced by Discrete Activation of Dorsal Mediastinal Cardiac Nerves in Canines

Cardinal

Armour

Bouchard

et al. 2010

Circ: Arrhythmia and Electrophysiology

Self Cite

View full text Add to dashboard Cite

Background-Chronotropic "vagal responses" elicited by high-frequency stimulation have been used to identify atrial targets for ablative treatment of atrial tachyarrhythmias (AT), whereas an anatomic approach consisting of extensive ablation of the ganglionated plexus areas has been proposed as an alternative. Therefore, there is a need for precise delineation of juxtacardiac nerves involved in AT initiation and clarification of their regional influences throughout the atria in relation to AT sites of origin, beyond chronotropic effects related to sinus node modulation. Methods and Results-Unipolar electrograms were recorded from 191 biatrial epicardial sites in 13 anesthetized canines, with concomitant left atrial endocardial recording from 63 sites in 5 of 13 animals. When electric stimuli were delivered to dorsal mediastinal nerves during the atrial refractory period, atrial premature depolarizations initiating AT were elicited in all animals, most frequently without prior sinus cycle length modification. Among 63 episodes, the sites of origin of early AT beats were localized to (1) the posterolateral left atrial wall in the pulmonary vein region (33%), (2) superior left atrial loci along the Bachmann bundle (55%), and (3) the region of Bachmann bundle insertion into the superior right atrial wall (11%). Moreover, the AT sites of origin were spatially concordant with regional waveform changes during the repolarization phase of unipolar recordings. AT induction and repolarization changes were abolished after atropine administration. Conclusions-Activation of individual dorsal mediastinal nerves induces AT arising from distinct sites of origin which are spatially concordant with regional atrial repolarization changes. (Circ Arrhythm Electrophysiol. 2010;3:511-520.)

show abstract

“…Overall, the data suggest that activation of mediastinal nerve inputs to the intrinsic cardiac nervous system engages a complex, interconnected neuronal system endowed with the capability of exerting widespread, redundant atrial (and ventricular) influences as well as discrete atrial effects [24]. It is also important to note that juxtacardiac nerves (including the dorsal mediastinal nerves) carry axons of both cholinergic and adrenergic efferent as well as afferent fibers derived from several extrinsic cardiac nerves [25,26].…”

Section: Functional Versus Anatomical Mapping Of Ganglionated Plexus mentioning

confidence: 99%

“…acetylcholinesterase (AChE) staining [9]. However, efferent projection patterns determined on this basis carry uncertain functional significance since the ganglionated plexuses are interconnected [29,30] and, moreover, their cardiac influences are spatially divergent [24]. In fact, we have reported evidence that, in the canine heart: (i) chronotropic effects can be mediated via pharmacological activation (nicotine) of any of the four main ganglionated plexuses associated with atrial tissues; (ii) effects on ventricular repolarization can identified in response to activation of such "atrial" ganglionated plexuses; and (iii) conversely, effects on atrial repolarization can be identified in response to activation of ganglionated plexuses associated with ventricular tissues [24].…”

Section: Functional Versus Anatomical Mapping Of Ganglionated Plexus mentioning

confidence: 99%

Mapping of Atrial Repolarization Changes and Tachyarrhythmia Sites of Origin During Activation of Mediastinal Nerve Inputs to the Intrinsic Cardiac Nervous System

Cardinal

Pagé

2012

Cardiac Mapping

Self Cite

View full text Add to dashboard Cite

Chronotropic, dromotropic or hypotensive "vagal responses" elicited by high frequency stimulation alone or in combination with anatomic data derived from the literature have been employed to identify juxtacardiac neural targets as adjunct therapy during ablation of myocardial substrates of paroxysmal atrial fibrillation. In particular, attention has been directed to the ganglionated plexuses nested in atrial epicardial fatty tissues as prime targets for ablation. Experimental studies in which atrial tachyarrhythmias were induced by stimulation of the mediastinal nerve inputs to the ganglionated plexuses in canines, show spatial concordance between the tachyarrhythmia sites of origin and the atrial distribution of repolarization changes determined from up to 255 simultaneously recorded unipolar electrograms. Such changes usually occurred in the absence of any chronotropic effect in response to left-sided nerve stimulation. Experimental studies also show that the atrial and ventricular ganglionated plexuses form an interconnected network exerting redundant control over sinus and atrioventricular node function as well as atrial refractoriness. It is concluded that ablative therapy targeting the intrinsic cardiac nervous system in individual patients can hardly be based on a priori anatomic generalizations and that functional measures derived from the entire atrial muscle surfaces (repolarization changes) should be required to identify putative neural targets. The clinical issueClinical studies support the notion that targeting juxtacardiac nerves may be useful adjunct therapy to pulmonary vein isolation and ablation of select atrial muscle structures for the treatment of paroxysmal atrial fibrillation [1][2][3]. Chronotropic (sinus node), dromotropic (atrioventricular [AV] node) or hypotensive "vagal responses" elicited by high frequency stimulation have been employed to identify neural atrial targets for ablation [1,2,4,5]. Alternatively, extensive ablation of putative ganglionated plexus areas has been proposed as a purely anatomical approach [6,7] based on published anatomic data [8,9] and, recently, in combination with high frequency stimulation of selected nerve sites to confirm neural activity [10]. Therefore, there is a need for precise delineation of juxtacardiac nerves involved in the initiation of atrial tachyarrhythmias and clarification of their regional functional influences throughout the atria in relation to tachyarrhythmia sites of origin, beyond chronotropic and dromotropic effects related to sinus node and AV node modulation. It is conceivable that clinically relevant neural sites might be missed if high frequency stimulation applied at such sites induced undetected regional changes in atrial refractoriness without inducing chronotropic, dromotropic or pressor responses.

show abstract

Spatially divergent cardiac responses to nicotinic stimulation of ganglionated plexus neurons in the canine heart

Cited by 64 publications

References 46 publications

The heart's ‘little brain’ controlling cardiac function in the rabbit

The heart's ‘little brain’ controlling cardiac function in the rabbit

Atrial Tachyarrhythmias and Repolarization Changes Induced by Discrete Activation of Dorsal Mediastinal Cardiac Nerves in Canines

Mapping of Atrial Repolarization Changes and Tachyarrhythmia Sites of Origin During Activation of Mediastinal Nerve Inputs to the Intrinsic Cardiac Nervous System

Contact Info

Product

Resources

About