Neuraxial Modulation for Refractory Ventricular Arrhythmias

Bourke, Tara; Vaseghi, Marmar; Michowitz, Yoav; Sankhla, Vineet; Shah, Mandar; Swapna, Nalla; Boyle, Noel G.; Mahajan, Aman; Narasimhan, Calambur; Lokhandwala, Yash; Shivkumar, Kalyanam

doi:10.1161/circulationaha.109.929703

Cited by 304 publications

(129 citation statements)

References 34 publications

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“…The TH/GAP43 value in the MI rats treated with NONRATT021972 siRNA was significantly decreased compared to the MI group. The modulation of cardiac sympathetic signaling is a major therapeutic strategy to prevent and treat the symptoms of angina pectoris in 50-60 % patients with coronary heart disease [48][49][50][51][52]. The NONRATT021972 siRNA treatment might decrease the abnormal innervations of the cardiac sympathetic nerves.…”

Section: Discussionmentioning

confidence: 99%

Long noncoding NONRATT021972 siRNA normalized abnormal sympathetic activity mediated by the upregulation of P2X7 receptor in superior cervical ganglia after myocardial ischemia

Zou

Liu

et al. 2016

Purinergic Signalling

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Previous studies showed that the upregulation of the P2X 7 receptor in cervical sympathetic ganglia was involved in myocardial ischemic (MI) injury. The dysregulated expression of long noncoding RNAs (lncRNAs) participates in the onset and progression of many pathological conditions. The aim of this study was to investigate the effects of a small interfering RNA (siRNA) against the NONRATT021972 lncRNA on the abnormal changes of cardiac function mediated by the up-regulation of the P2X 7 receptor in the superior cervical ganglia (SCG) after myocardial ischemia. When the MI rats were treated with NONRATT021972 siRNA, their increased systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), low-frequency (LF) power, and LF/HF ratio were reduced to normal levels. However, the decreased high-frequency (HF) power was increased. GAP43 and tyrosine hydroxylase (TH) are markers of nerve sprouting and sympathetic nerve fibers, respectively. We found that the TH/GAP43 value was significantly increased in the MI group. However, it was reduced after the MI rats were treated with NONRATT021972 siRNA. The serum norepinephrine (NE) and epinephrine (EPI) concentrations were decreased in the MI rats that were treated with NONRATT021972 siRNA. Meanwhile, the increased P2X 7 mRNA and protein levels and the increased p-ERK1/2 expression in the SCG were also reduced. NONRATT021972 siRNA treatment inhibited the P2X 7 agonist BzATPactivated currents in HEK293 cells transfected with pEGFP-P2X 7 . Our findings suggest that NONRATT021972 siRNA could decrease the upregulation of the P2X 7 receptor and improve the abnormal changes in cardiac function after myocardial ischemia.

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Section: Discussionmentioning

confidence: 99%

Long noncoding NONRATT021972 siRNA normalized abnormal sympathetic activity mediated by the upregulation of P2X7 receptor in superior cervical ganglia after myocardial ischemia

Zou

Liu

et al. 2016

Purinergic Signalling

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“…Differential intra-ventricular effects also exist, with left SNS resulting in a greater reduction of APD at the base of the left ventricle (LV) (Winter et al 2012). This has important clinical implications as left thoracic sympathetic denervation may serve as effective anti-arrhythmic therapy in post-infarct patients (Schwartz et al 1992), long QT Syndrome (Schwartz et al 2004), catecholaminergic polymorphic VT (Wilde et al 2008) and VT storm (Bourke et al 2010). …”

Section: Laterality and Heterogeneous Innervationmentioning

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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“…61 Clinically, disrupting cardiac sympathetic innervation either through epidural anaesthesia or through cardiac sympathetic denervation has been used to treat patients with refractory ventricular arrhythmias. 62 Myocardial infarction interrupts autonomic innervation in the area of the infarct, with the subsequent development of sympathetic hypersensitivity, nerve sprouting and heterogeneous gradients of sympathetic innervation around the infarct. 57 NCT01362725).…”

Section: Spinal Cord Stimulation and Ventricular Electrophysiologymentioning

confidence: 99%

Device-Based Approaches to Modulate the Autonomic Nervous System and Cardiac Electrophysiology

Hucker

Singh

Parks

et al. 2014

Arrhythm Electrophysiol Rev

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The interplay between the central nervous system and cardiac electrophysiology is fundamental, and becomes obvious each time one's pulse quickens in response to stress. Normally, cardiac neurohormonal regulation is accomplished through the balanced effects of sympathetic and parasympathetic autonomic stimulation, along with the hormonal regulation of the renin-angiotensinaldosterone system (RAAS). Autonomic and hormonal input modulate multiple facets of cellular electrophysiology -action potential duration, ion channel kinetics and intracellular calcium dynamics (just to name a few) -which translate into macroscopic manifestations of autonomic modulation such as heart rate variability, atrioventricular (AV) conduction time and QT interval variability.1 Therefore, it is no surprise that neurohormonal regulation of cardiac electrophysiology is an area of active investigation for its potential antiarrhythmic effects. Recent reviews have focused on the efficacy of neurohormonal modulation, via non-pharmacological methods, to enhance heart failure treatment. 2,3 This review will attempt to provide a state-of-the-art on the potential antiarrhythmic efficacy of renal artery denervation, spinal cord stimulation and direct vagal stimulation. Neurohormonal Control in the Normal and Failing HeartAutonomic control of cardiac physiology is often conceptualised as parasympathetic (cholinergic) and sympathetic (adrenergic) innervation existing in a 'yin and yang' balance under normal circumstances; however, this concept may be over-simplified. 4 In reality, the intrinsic cardiac nervous system, composed of several ganglia located primarily posterior to the atria, likely acts as a 'little brain' of the heart -it provides efferent input to the myocardium, collects afferent signals on a beat-to-beat basis and performs some integrative functions on its own, all under the tonic modulation of extrinsic sympathetic and parasympathetic input (see Figure 1). 4-8The ganglia are predominantly composed of cholinergic neurons; however, sympathetic efferent neurons are also present. Due to the complex interconnectivity between the ganglia, afferent mechanosensory, nociceptive and chemosensory signals from all four chambers of the heart may be processed within a single ganglion. 4 Such interconnectivity implies that predicting the effect of stimulation or ablation of a particular ganglion may be difficult, because each ganglion performs multiple functions. 7,9Abstract Alterations in resting autonomic tone can be pathogenic in many cardiovascular disease states, such as heart failure and hypertension.Indeed, autonomic modulation by way of beta-blockade is a standard treatment of these conditions. There is a significant interest in developing non-pharmacological methods of autonomic modulation as well. For instance, clinical trials of vagal stimulation and spinal cord stimulation in the treatment of heart failure are currently underway, and renal denervation has been studied recently in the treatment of resistant hypertension. Notably, autonom...

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Neuraxial Modulation for Refractory Ventricular Arrhythmias

Cited by 304 publications

References 34 publications

Long noncoding NONRATT021972 siRNA normalized abnormal sympathetic activity mediated by the upregulation of P2X7 receptor in superior cervical ganglia after myocardial ischemia

Long noncoding NONRATT021972 siRNA normalized abnormal sympathetic activity mediated by the upregulation of P2X7 receptor in superior cervical ganglia after myocardial ischemia

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

Device-Based Approaches to Modulate the Autonomic Nervous System and Cardiac Electrophysiology

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