Autonomic mechanisms and sudden death. New insights from analysis of baroreceptor reflexes in conscious dogs with and without a myocardial infarction.

Schwartz, Peter J.; Vanoli, Emilio; Stramba-Badiale, Marco; Ferrari, Gaetano M. De; Billman, George E.; Foreman, Robert D.

doi:10.1161/01.cir.78.4.969

Cited by 527 publications

(276 citation statements)

References 71 publications

(15 reference statements)

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“…67 Just as in HRV, BRS was shown to be reduced after MI and to predispose to ventricular fibrillation first in dog MI models. 66 These studies were carried forward to humans, where BRS was found to be lower in patients after MI than in control subjects, but the reduction was transient and appeared to return to baseline levels within 3 months, similar to the improvement seen in HRV and decreasing risk of SCD. 74 The potential prognostic value of BRS was established in several human studies showing that a severely depressed BRS (<3 milliseconds/mm Hg) was associated with high mortality due to a high risk of arrhythmic events.…”

Section: Baroreflex Sensitivitymentioning

confidence: 88%

“…Depressed baroreflex sensitivity (BRS) and heart rate variability (HRV), reflections of parasympathetic innervations, have been associated in humans and animal models of MI with a greater susceptibility to ventricular fibrillation during and after ischemic episodes. 66 Heart rate variability primarily reflects tonic vagal activity, whereas BRS measures predominantly reflex vagal activity in response to stressors. Middleaged healthy men with high resting heart rates (>75 beats per minute) had a 3.8-fold increase in the risk of SCD compared with those with low basal heart rates (<60 beats per minute), with the risk of SCD increasing linearly with increasing resting heart rates over 23 years of followup, suggesting that high parasympathetic tone is protective against SCD.…”

Section: Cardiac Parasympathetic Nervous System Dysfunction As Manifementioning

confidence: 99%

“…Middleaged healthy men with high resting heart rates (>75 beats per minute) had a 3.8-fold increase in the risk of SCD compared with those with low basal heart rates (<60 beats per minute), with the risk of SCD increasing linearly with increasing resting heart rates over 23 years of followup, suggesting that high parasympathetic tone is protective against SCD. 66 …”

Section: Cardiac Parasympathetic Nervous System Dysfunction As Manifementioning

confidence: 99%

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The Role of the Autonomic Nervous System in Sudden Cardiac Death

Vaseghi

Shivkumar²

2008

Progress in Cardiovascular Diseases

328

233

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The cardiac autonomic nervous system consists of 2 branches-the sympathetic and the parasympathetic systems-that work in a delicately tuned, yet opposing fashion in the heart. This extrinsic control mechanism can dominate intrinsic regulatory mechanisms that modulate heart rate and cardiac output. These branches differ in their neurotransmitters (norepinephrine and acetylcholine) and exert stimulatory or inhibitory effects on target tissue via adrenergic and muscarinic receptors. Stimulation of the sympathetic branch exerts facilitatory effects on function, increasing heart rate and myocardial contractility, whereas the stimulation of the parasympathetic branch exerts inhibitory effects that decrease heart rate and contractility. The interplay between these two branches is complex and susceptible to control at several levels, from centrally mediated baroreceptors and chemoreceptors to local interneuronal interactions.Alterations in autonomic function occur in several interrelated cardiac conditions including sudden cardiac death, congestive heart failure, diabetic neuropathy, and myocardial ischemia. Although the full extent of these changes has not been elucidated, multiple autonomic remodeling mechanisms have been observed at both the neuronal fiber and myocardial cellular level that contribute to an arrhythmogenic substrate. We describe the anatomy of both systems in this review. However, the review will premdominantly focus on the sympathetic system, whose role in the modulation of cardiac arrhythmias is slightly better delineated. Cardiac Autonomic Innervation: NeuroanatomyBoth branches of the autonomic nervous system are composed of both afferent and efferent as well interneuronal fibers (Fig 1). Sympathetic innervation originates mainly in the right and left stellate ganglia. These fibers travel along the epicardial vascular structures of the heart and penetrate into the underlying myocardium similar to coronary vessels and end as sympathetic nerve terminals reaching the endocardium. Based on norepinephrine content studies, a gradient exists in sympathetic innervation from atria to the ventricles and from base to apex of the heart. Therefore, the atria are most densely innervated, but the ventricles are also supplied with a sympathetic network, most densely at the base. 1 Parasympathetic effects are carried by the right and left vagus nerves, originating in the medulla. The vagus nerve further divides into the superior and inferior cardiac nerves, finally merging with the postganglionic sympathetic neurons to form a plexus of nerves at the base of the heart, known as the cardiac plexus. In contrast to sympathetic neurons, after parasympathetic fibers cross the atrioventricular (AV) groove along the surface of the heart,

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Section: Baroreflex Sensitivitymentioning

confidence: 88%

Section: Cardiac Parasympathetic Nervous System Dysfunction As Manifementioning

confidence: 99%

Section: Cardiac Parasympathetic Nervous System Dysfunction As Manifementioning

confidence: 99%

See 1 more Smart Citation

The Role of the Autonomic Nervous System in Sudden Cardiac Death

Vaseghi

Shivkumar²

2008

Progress in Cardiovascular Diseases

328

233

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“…Based on the fact that the occurrence of fatal ventricular arrhythmias is accompanied by a marked decrease of parasympathetic activity in CHF, some studies demonstrate that decreased parasympathetic activity is correlated with malignant ventricular arrhythmogenesis in the CHF state 11, 46, 47, 48. Recent studies have also found that the parasympathetic activation induced by vagal nerve stimulation prevents fatal ventricular arrhythmias and improves survival rates in animal CHF models 17, 18, 19.…”

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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“…Considerable amount of basic and clinical data attests to the critical role of the autonomic nervous system in SCD mechanisms [15][16][17]. One potential trigger for fatal arrhythmias in patients with ischemic heart disease or HF may come from an imbalance of the parasympathetic and sympathetic nervous systems, the latter being mediated by Cardiac β 1 -and β 2 -adrenergic receptors.…”

Section: β-Adrenergic Receptor Signaling Cascadementioning

confidence: 99%

Genomics, heart failure and sudden cardiac death

Darbar

2008

Heart Fail Rev

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Sudden cardiac death (SCD) is among the most common causes of death in developed countries throughout the world. Despite decreased overall cardiac mortality, SCD vrates appear to be increasing in concert with escalating global prevalence of coronary disease and heart failure, the two major conditions predisposing to SCD. This unfavorable trend is a consequence of our inability to identify those who will die suddenly from lethal ventricular arrhythmias and to develop effective therapies for all populations at risk. The known risk factors for SCD lack the predictive power needed to generate preventive strategies for the large number of fatal arrhythmic events that occur among lowerrisk subsets of the population. Even among recognized high-risk subsets, prediction of SCD remains challenging. With the exception of the implantable cardioverter defibrillator (ICD) there are few effective strategies for the prevention and treatment of SCD. This article discusses the prospect of genomic science as an approach to the identification of patients at high-risk for SCD. While the final common pathway for SCD is malignant ventricular arrhythmias, there are many potential contributors, pathways, and mechanisms by which common genetic variants (polymorphisms) could affect initiation and propagation of life-threatening cardiac arrhythmias. Recent advances in genomic medicine now provide us with novel approaches to both identify candidate genes/pathways and relatively common polymorphisms which may predispose patients to increased risk for SCD. Improved understanding of the relationship between common polymorphisms and SCD will not only improve risk stratification such that ICDs can be targeted to those patients most likely to benefit from them but also provide new insight into the pathophysiology of SCD. KeywordsSudden cardiac death; Genomics; Heart failure; Single nucleotide polymorphisms Heart failure and SCD Heart failure (HF) afflicts approximately 5 million people in the United States, with 550,000 new cases reported annually, but as the population ages both the incidence and prevalence is expected to rise [1]. HF is associated with high mortality and is reportedly responsible for 300,000 deaths annually in the US [1]. Prior to advent of neuro-hormonal antagonists, the mean duration of survival after onset of HF was 1.7 years for men and 3.2 years for women, with only half of patients still alive after 5 years of onset [2]. The two modes of death in patients with HF are circulatory failure due to progressive left ventricular (LV) dysfunction associated with gradual worsening of symptoms, or sudden cardiac death (SCD) in relatively clinically stable patients [3].Although the proportion of sudden deaths in published trials varies significantly, probably due to varying interpretations of reported modes of death, clinical trials data suggests that SCD accounts for approximately one-third of all HF deaths [4]. Epidemiologic evidence from the Framingham heart study suggests that about one-half of all deaths due to HF occur...

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Autonomic mechanisms and sudden death. New insights from analysis of baroreceptor reflexes in conscious dogs with and without a myocardial infarction.

Cited by 527 publications

References 71 publications

The Role of the Autonomic Nervous System in Sudden Cardiac Death

The Role of the Autonomic Nervous System in Sudden Cardiac Death

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

Genomics, heart failure and sudden cardiac death

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Autonomic mechanisms and sudden death. New insights from analysis of baroreceptor reflexes in conscious dogs with and without a myocardial infarction.

Cited by 527 publications

References 71 publications

The Role of the Autonomic Nervous System in Sudden Cardiac Death

The Role of the Autonomic Nervous System in Sudden Cardiac Death

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

Genomics, heart failure and sudden cardiac death

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Product

Resources

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