Quantitative analysis of parasympathetic innervation of the porcine heart

Ulphani, Joseph S.; Cain, Jack H.; Inderyas, Firdous; Gordon, David; Gikas, P.; Shade, Gregory; Mayor, David; Arora, Rishi; Kadish, Alan H.; Goldberger, Jeffrey J.

doi:10.1016/j.hrthm.2010.03.043

Cited by 66 publications

(50 citation statements)

References 23 publications

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“…Overall, both right and left VNS caused small increases in DOR on the epicardium. This may be due to the bradycardia caused by VNS (28) or to the more sparse density of parasympathetic nerve fibers on the epicardium (51). In fact, functional parasympathetic innervation of the endocardium was greater than the epicardium, consistent with a histological study (51) showing that the endocardium has a greater density of parasympathetic fibers.…”

supporting

confidence: 59%

“…This may be due to the bradycardia caused by VNS (28) or to the more sparse density of parasympathetic nerve fibers on the epicardium (51). In fact, functional parasympathetic innervation of the endocardium was greater than the epicardium, consistent with a histological study (51) showing that the endocardium has a greater density of parasympathetic fibers. Furthermore, parasympathetic fibers are thought to run from the endocardium to the epicardium, as supported by the observation that denervation of the epicardium does not reduce the endocardial ventricular response to VNS (34).…”

supporting

confidence: 59%

“…Indeed, parasympathetic innervation of the ventricular myocardium was considered minimal for many years. Histological studies have now confirmed evidence of abundant ventricular parasympathetic innervation (24,26,51). Previous studies of ventricular repolarization during VNS were limited to using a small number of electrodes (35), extrastimulus pacing (33), or VF intervals (41): techniques that can alter autonomic tone (23) and do not provide detailed spatial data.…”

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confidence: 98%

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Electrophysiological effects of right and left vagal nerve stimulation on the ventricular myocardium

Yamakawa

Rajendran

et al. 2014

American Journal of Physiology-Heart and Circulatory Physiology

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(VNS) has been proposed as a cardioprotective intervention. However, regional ventricular electrophysiological effects of VNS are not well characterized. The purpose of this study was to evaluate effects of right and left VNS on electrophysiological properties of the ventricles and hemodynamic parameters. In Yorkshire pigs, a 56-electrode sock was used for epicardial (n ϭ 12) activation recovery interval (ARI) recordings and a 64-electrode catheter for endocardial (n ϭ 9) ARI recordings at baseline and during VNS. Hemodynamic recordings were obtained using a conductance catheter. Right and left VNS decreased heart rate (84 Ϯ 5 to 71 Ϯ 5 beats/min and 84 Ϯ 4 to 73 Ϯ 5 beats/min), left ventricular pressure (89 Ϯ 9 to 77 Ϯ 9 mmHg and 91 Ϯ 9 to 83 Ϯ 9 mmHg), and dP/dt max (1,660 Ϯ 154 to 1,490 Ϯ 160 mmHg/s and 1,595 Ϯ 155 to 1,416 Ϯ 134 mmHg/s) and prolonged ARI (327 Ϯ 18 to 350 Ϯ 23 ms and 327 Ϯ 16 to 347 Ϯ 21 ms, P Ͻ 0.05 vs. baseline for all parameters and P ϭ not significant for right VNS vs. left VNS). No anteriorposterior-lateral regional differences in the prolongation of ARI during right or left VNS were found. However, endocardial ARI prolonged more than epicardial ARI, and apical ARI prolonged more than basal ARI during both right and left VNS. Changes in dP/dt max showed the strongest correlation with ventricular ARI effects (R 2 ϭ 0.81, P Ͻ 0.0001) than either heart rate (R 2 ϭ 0.58, P Ͻ 0.01) or left ventricular pressure (R 2 ϭ 0.52, P Ͻ 0.05). Therefore, right and left VNS have similar effects on ventricular ARI, in contrast to sympathetic stimulation, which shows regional differences. The decrease in inotropy correlates best with ventricular electrophysiological effects.vagal nerve stimulation; ventricle; repolarization THE AUTONOMIC NERVOUS SYSTEM plays a significant role in the genesis and persistence of ventricular arrhythmias (54, 59). Sympathetic activation is proarrhythmic (16,32,53), whereas parasympathetic activation is thought to be cardioprotective (17, 31). The vagal nerve trunk provides important cardiomotor efferent fibers to the heart and also carries afferent signals from the heart. Vagal nerve stimulation (VNS) has been shown to decrease infarct size (48), reduce the ventricular fibrillation (VF) threshold (39), and decrease the incidence of ventricular arrhythmias and mortality during ischemia (13,27,38,52). Furthermore, a preserved parasympathetic reflex has been reported to be protective during myocardial infarction (46). Stimulation of the right vagal nerve (RVN) has shown benefits in a series of patients with cardiomyopathy and is undergoing evaluation in clinical trials (20,47). The mechanisms of the antiarrhythmic effects of VNS are less clear and are thought to be multifactorial, with a decrease in heart rate (HR) (15), release of nitric oxide (9), and antagonism of the sympathetic nervous system all thought to play a role (8,30,49).Modulation of repolarization by sympathetic nerve stimulation has been well characterized (1,25,41,55,58). However, the effects of parasympatheti...

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supporting

confidence: 59%

supporting

confidence: 59%

mentioning

confidence: 98%

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Electrophysiological effects of right and left vagal nerve stimulation on the ventricular myocardium

Yamakawa

Rajendran

et al. 2014

American Journal of Physiology-Heart and Circulatory Physiology

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“…Thus far, most of the studies used the analysis of heart‐rate variability and arterial baroreflex sensitivity to evaluate cardiac sympathetic and parasympathetic autonomic activity in physiological and pathophysiological conditions 38. Although traditional teaching has stated that cardiac vagal postganglionic nerves regulate the heart through slowing sinus rate and atrioventricular conduction, with little influence on ventricles, and ventricular vagal innervation is considered to be sparse,18, 39 newer histological techniques have challenged this traditional principle and affirmed dense vagal innervation in the ventricle from all species 18, 40, 41, 42, 43. Recent studies have demonstrated that functionally significant parasympathetic control of ventricular contractile function and excitability exists in rats, and vagal preganglionic neurons of the dorsal motor nucleus contribute to the vagal control of ventricular contractility and excitability 44, 45.…”

Section: Discussionmentioning

confidence: 99%

Reduced N‐Type Ca ²⁺ Channels in Atrioventricular Ganglion Neurons Are Involved in Ventricular Arrhythmogenesis

Zhang

Cao

et al. 2018

JAHA

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BackgroundAttenuated cardiac vagal activity is associated with ventricular arrhythmogenesis and related mortality in patients with chronic heart failure. Our recent study has shown that expression of N‐type Ca2+ channel α‐subunits (Cav2.2‐α) and N‐type Ca2+ currents are reduced in intracardiac ganglion neurons from rats with chronic heart failure. Rat intracardiac ganglia are divided into the atrioventricular ganglion (AVG) and sinoatrial ganglion. Ventricular myocardium receives projection of neuronal terminals only from the AVG. In this study we tested whether a decrease in N‐type Ca2+ channels in AVG neurons contributes to ventricular arrhythmogenesis.Methods and ResultsLentiviral Cav2.2‐α shRNA (2 μL, 2×107 pfu/mL) or scrambled shRNA was in vivo transfected into rat AVG neurons. Nontransfected sham rats served as controls. Using real‐time single‐cell polymerase chain reaction and reverse‐phase protein array, we found that in vivo transfection of Cav2.2‐α shRNA decreased expression of Cav2.2‐α mRNA and protein in rat AVG neurons. Whole‐cell patch‐clamp data showed that Cav2.2‐α shRNA reduced N‐type Ca2+ currents and cell excitability in AVG neurons. The data from telemetry electrocardiographic recording demonstrated that 83% (5 out of 6) of conscious rats with Cav2.2‐α shRNA transfection had premature ventricular contractions (P<0.05 versus 0% of nontransfected sham rats or scrambled shRNA‐transfected rats). Additionally, an index of susceptibility to ventricular arrhythmias, inducibility of ventricular arrhythmias evoked by programmed electrical stimulation, was higher in rats with Cav2.2‐α shRNA transfection compared with nontransfected sham rats and scrambled shRNA‐transfected rats.ConclusionsA decrease in N‐type Ca2+ channels in AVG neurons attenuates vagal control of ventricular myocardium, thereby initiating ventricular arrhythmias.

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“…Dense parasympathetic innervation is demonstrated in all species studied including the mouse (Rysevaite et al 2011), guinea pig (Batulevicius et al. 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 2005), rabbit (Pauziene et al 2016), cat (Johnson et al 2004, dog (Pauza et al 2002), pig (Ulphani et al 2010), sheep (Saburkina et al 2010) and human ventricle (Pauza et al 2000;Kawano et al 2003).…”

Section: The Parasympathetic Nervous System and Ventricular Arrhythmiasmentioning

confidence: 99%

Neuro-cardiac interaction in malignant ventricular arrhythmia and sudden cardiac death

2016

Autonomic Neuroscience

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Sudden cardiac death as a result of lethal ventricular arrhythmias is a major cause of death in cardiac diseases such as heart failure and prior myocardial infarct. Activity of the autonomic nervous system is often abnormal where sympathetic activity is upregulated and vagal activity reduced in these conditions. The abnormal autonomic state has been shown to be a strong prognostic marker of increased mortality and propensity to lethal arrhythmias, for which there is no effective prevention. Research effort over the years has established good evidence for a causal link between autonomic disturbance and ventricular arrhythmias. However, the detailed electrophysiological mechanisms by which ventricular fibrillation occurs are still not clear and molecular processes which are modulated by autonomic nerve influences that either predispose the heart to or protect it from these arrhythmias are not fully understood. This review presents data from studies investigating the link between activity of the autonomic nervous system and ventricular arrhythmias, from seminal findings in classical studies to ongoing investigations, in the quest for a better understanding of the arrhythmogenic mechanisms underlying neurocardiac interactions with a view to the development of effective preventative and therapeutic strategies which are very much needed.

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Quantitative analysis of parasympathetic innervation of the porcine heart

Cited by 66 publications

References 23 publications

Electrophysiological effects of right and left vagal nerve stimulation on the ventricular myocardium

Electrophysiological effects of right and left vagal nerve stimulation on the ventricular myocardium

Reduced N‐Type Ca ²⁺ Channels in Atrioventricular Ganglion Neurons Are Involved in Ventricular Arrhythmogenesis

Neuro-cardiac interaction in malignant ventricular arrhythmia and sudden cardiac death

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Quantitative analysis of parasympathetic innervation of the porcine heart

Cited by 66 publications

References 23 publications

Electrophysiological effects of right and left vagal nerve stimulation on the ventricular myocardium

Electrophysiological effects of right and left vagal nerve stimulation on the ventricular myocardium

Reduced N‐Type Ca 2+ Channels in Atrioventricular Ganglion Neurons Are Involved in Ventricular Arrhythmogenesis

Neuro-cardiac interaction in malignant ventricular arrhythmia and sudden cardiac death

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Product

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Reduced N‐Type Ca ²⁺ Channels in Atrioventricular Ganglion Neurons Are Involved in Ventricular Arrhythmogenesis