Nerve Sprouting and Sudden Cardiac Death

Cao, Ji‐Min; Chen, Lan S.; KenKnight, Bruce H.; Ohara, Toshihiko; Lee, Moon Hyoung; Tsai, Jerome; Lai, William W.; Karagueuzian, Hrayr S.; Wolf, Paul L.; Fishbein, Michael C.; Chen, Peng Sheng

doi:10.1161/01.res.86.7.816

Cited by 387 publications

(400 citation statements)

References 31 publications

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“…Although the present study confirms peri-infarct hyperinnervation (Cao, et al, 2000a;Cao, et al, 2000b), other studies have reported reduced cardiac sympathetic innervation after infarction (Barber, et al, 1983;Igawa, et al, 2000;Li, et al, 2004). These differences may be related to the extent of infarction as larger infarcts can result in frank congestive heart failure, and this has been linked to cardiac NGF depletion and diminished sympathetic axon density (Kaye, et al, 2000;Qin, et al, 2002).…”

Section: Selectivity Of Post-infarct Hyperinnervationsupporting

confidence: 59%

“…NGF is a potent growth and survival factor for sympathetic neurons (Korsching and Thoenen, 1985;Glebova and Ginty, 2004). Recent evidence indicates that NGF expression is up-regulated in the region of the infarction (Hiltunen, et al, 2001;Zhou, et al, 2004), and infusion of NGF into the stellate ganglion results in cardiac hyperinnervation in canine hearts (Cao, et al, 2000b). However, the cell types involved in post-infarct cardiac NGF production and the neural selectivity of the response are not well defined.…”

Section: Introductionmentioning

confidence: 99%

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Sympathetic hyperinnervation and inflammatory cell NGF synthesis following myocardial infarction in rats

et al. 2006

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Sympathetic hyperinnervation occurs in human ventricular tissue after myocardial infarction and may contribute to arrhythmias. Aberrant sympathetic sprouting is associated with elevated nerve growth factor (NGF) in many contexts, including ventricular hyperinnervation. However, it is unclear whether cardiomyocytes or other cell types are responsible for increased NGF synthesis. In this study, left coronary arteries were ligated and ventricular tissue examined in rats 1-28 days post-infarction. Infarct and peri-infarct tissue was essentially devoid of sensory and parasympathetic nerves at all time points. However, areas of increased sympathetic nerve density were observed in the peri-infarct zone between post-ligation days 4-14. Hyperinnervation occurred in regions containing accumulations of macrophages and myofibroblasts. To assess whether these inflammatory cells synthesize NGF, sections were processed for NGF in situ hybridization and immunohistochemistry. Both macrophage1 antigen-positive macrophages and α-smooth muscle actin immunoreactive myofibroblasts expressed NGF in areas where they were closely proximate to sympathetic nerves. To investigate whether NGF produced by peri-infarct cells induces sympathetic outgrowth, we cocultured adult sympathetic ganglia with peri-infarct explants. Neurite outgrowth from sympathetic ganglia was significantly greater at post-ligation days 7-14 as compared to control tissue. Addition of an NGF function-blocking antibody prevented the increased neurite outgrowth induced by periinfarct tissue. These findings provide evidence that inflammatory cell NGF synthesis plays a causal role in sympathetic hyperinnervation following myocardial infarction.

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Section: Selectivity Of Post-infarct Hyperinnervationsupporting

confidence: 59%

Section: Introductionmentioning

confidence: 99%

Sympathetic hyperinnervation and inflammatory cell NGF synthesis following myocardial infarction in rats

et al. 2006

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“…Furthermore, NGF infusion to the left stellate ganglion resulted in nerve sprouting in normal dogs but did not cause ventricular arrhythmias or SCD. 46 A differential response of QTc and ventricular arrhythmia was seen when the left vs the right stellate ganglia were infused with NGF. Infusion into the left stellate ganglion cause sympathetic nerve sprouting on immunocytochemical staining in the left ventricle, with resulting QTc prolongation and sudden cardiac death in 50% of the experimental dogs.…”

Section: Myocardial Infarction Heart Failure and Sympathetic Innervmentioning

confidence: 99%

The Role of the Autonomic Nervous System in Sudden Cardiac Death

Vaseghi

Shivkumar²

2008

Progress in Cardiovascular Diseases

336

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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“…A study in dogs by Cao et al showed that injection of nerve growth factor in the vicinity of the left stellate ganglion increased the density of cardiac sympathetic fibres significantly and led to an increased incidence of ventricular dysrhythmias. 2 Later, Cao's group and others described similar cardiac sympathetic hyperinnervation in both adults and animals, including a history of ventricular arrhythmias and sudden cardiac death. [3][4][5] The patient described in this report suffered from both cardiac ischemia and obstructive sleep apnea, both of which lead to enhanced sympathetic output, nerve sprouting, and arrhythmogenic regional heterogeneities of sympathetic innervation.…”

Section: Discussionmentioning

confidence: 97%

Bilateral thoracic sympathetic block for refractory polymorphic tachycardia

Allen

Weaver

Burkey

2011

Can J Anesth/J Can Anesth

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Introduction Extensive evidence has established a link between sympathetic nervous system hyperactivity, ventricular arrhythmias, and sudden cardiac death. For this reason, cardiac sympathectomy is often beneficial in the treatment of patients at high risk for ventricular ectopy, although it involves an invasive procedure associated with potential morbidity. We report a case in which we used guided lytic thoracic sympathetic block in a patient with underlying cardiomyopathy and refractory polymorphic ventricular tachycardia. Clinical features A 74-yr-old African American male with ischemic cardiomyopathy presented with refractory episodes of ventricular tachycardia despite maximal medical therapy involving antiarrhythmic drugs and previous interventions, including endovascular epicardial ablation and open cryoablation via sternotomy. During his inpatient admission, the patient developed sustained ventricular tachycardia associated with cardiac depression requiring vasopressors. An open thoracoscopic sympathectomy was considered as a possible treatment, but in our view, the patient would not tolerate this procedure. As an alternative, the pain medicine team successfully performed a lytic thoracic sympathetic block. Subsequently, the patient demonstrated a period of clinical improvement with no apparent morbidity related to the procedure. Conclusion Lytic thoracic sympathetic blockade is a novel technique for the treatment of sympathetically mediated ventricular tachycardia, and it is less invasive than other types of cardiac sympathectomy. Additional studies are required to evaluate this treatment as a viable alternative in patients at high risk for ventricular ectopy. This report suggests the feasibility of this approach and the potential for minimal morbidity in cases of refractory ventricular arrhythmias. RésuméIntroduction De nombreuses donne´es probantes ont e´tabli qu'il existait un lien entre l'hyperactivite´du syste`me nerveux sympathique, les arythmies ventriculaires et la mort cardiaque subite. Pour cette raison, la sympathectomie cardiaque est souvent be´ne´fique pour traiter les patients pre´sentant un risque e´leve´d'ectopie ventriculaire, en de´pit du fait qu'il s'agisse d'une intervention effractive qui peut entraıˆner une morbidite´. Nous rapportons un cas dans lequel nous avons re´alise´un bloc sympathique thoracique lytique guide´chez un patient atteint d'une cardiomyopathie sous-jacente ainsi que d'une tachycardie ventriculaire polymorphe re´fractaire. É léments cliniques Un homme de 74 ans d'origine afro-ame´ricaine souffrant de cardiomyopathie ische´mique a manifeste´des e´pisodes re´fractaires de tachycardie ventriculaire malgre´un traitement me´dical maximal comportant des me´dicaments anti-arythmiques et des interventions par le passe´, notamment une ablation e´picardique endovasculaire et une cryoablation par voie ouverte via sternotomie. Pendant son hospitalisation, le patient a manifeste´une tachycardie ventriculaire soutenue associe´e à une de´pression cardiaque et ne´cessitant...

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Nerve Sprouting and Sudden Cardiac Death

Cited by 387 publications

References 31 publications

Sympathetic hyperinnervation and inflammatory cell NGF synthesis following myocardial infarction in rats

Sympathetic hyperinnervation and inflammatory cell NGF synthesis following myocardial infarction in rats

The Role of the Autonomic Nervous System in Sudden Cardiac Death

Bilateral thoracic sympathetic block for refractory polymorphic tachycardia

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