Cardiac spinal deafferentation reduces the susceptibility to sustained ventricular tachycardia in conscious rats

Lujan, Heidi L.; Krishnan, Sandhya; DiCarlo, Stephen E.

doi:10.1152/ajpregu.00140.2011

Cited by 7 publications

(7 citation statements)

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“…Furthermore, myocardial ischemia produces metabolites that evoke a powerful sympathetic reflex that increases arterial pressure, heart rate, ST‐segment, and double product (Lujan et al. ). This cardiac spinal reflex is analogous to the muscle metaboreflex observed in man, rat, and other mammals (Alam and Smirk ; Collins and DiCarlo ).…”

Section: Discussionmentioning

confidence: 99%

“…Transection of the dorsal roots disrupts this excitatory cardiac sympathetic reflex and reduces heart rate and arterial pressure during myocardial ischemia (Lujan et al. ). In addition, cardiac output and arterial pressure are reduced during myocardial ischemia which initiates a dramatic arterial baroreflex‐mediated increase in sympathetic outflow and decrease in parasympathetic outflow to the heart as well as an increased sympathetic outflow to the vasculature.…”

Section: Introductionmentioning

confidence: 99%

“…Accordingly, the tolerance to coronary artery occlusion is expected to be markedly impaired in T 5 X mice (Lujan et al. ).…”

Section: Introductionmentioning

confidence: 99%

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Fundamental hemodynamic mechanisms mediating the response to myocardial ischemia in conscious paraplegic mice: cardiac output versus peripheral resistance

Lujan

DiCarlo

2017

Physiological Reports

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Autonomic dysfunction, a relative sedentary lifestyle, a reduced muscle mass and increased adiposity leads to metabolic abnormalities that accelerate the development of coronary artery disease (CAD) in individuals living with spinal cord injury (SCI). An untoward cardiac incident is related to the degree of CAD, suggesting that the occurrence of a significant cardiac event is significantly higher for individuals with SCI. Thus, understanding the fundamental hemodynamic mechanisms mediating the response to myocardial ischemia has the potential to positively impact individuals and families living with SCI. Accordingly, we systematically investigated if thoracic level 5 spinal cord transection (T5X; paraplegia) alters the arterial blood pressure response to coronary artery occlusion and if the different arterial blood pressure responses to coronary artery occlusion between intact and paraplegic mice are mediated by changes in cardiac output and or systemic peripheral resistance and whether differences in cardiac output are caused by changes in heart rate and or stroke volume. To achieve this goal, the tolerance to 3 min of coronary artery occlusion was determined in conscious intact and paraplegic mice. Paraplegic mice had an impaired ability to maintain arterial blood pressure during coronary artery occlusion as arterial pressure fell to near lethal levels by 1.38 ± 0.64 min. The lower arterial pressure was mediated by a lower cardiac output as systemic peripheral resistance was elevated in paraplegic mice. The lower cardiac output was mediated by a reduced heart rate and stroke volume. These results indicate that in paraplegic mice, the arterial pressure response to coronary artery occlusion is hemodynamically mediated primarily by cardiac output which is determined by heart rate and stroke volume.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Fundamental hemodynamic mechanisms mediating the response to myocardial ischemia in conscious paraplegic mice: cardiac output versus peripheral resistance

Lujan

DiCarlo

2017

Physiological Reports

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“…In rats, disrupting the T1-T5 dorsal root ganglia to interrupt this reflex arc decreased the time to onset of ventricular arrhythmias. 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.…”

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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Section: Spinal Cord Stimulation and Ventricular Electrophysiologymentioning

confidence: 99%

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

Hucker¹,

Singh²,

Parks³

et al. 2011

Arrhythmia &Amp; Electrophysiology Review

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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 Heart Autonomic 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 oversimplified. 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). 4-8 The 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. 7,9

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Cardiac spinal deafferentation reduces the susceptibility to sustained ventricular tachycardia in conscious rats

Cited by 7 publications

References 78 publications

Fundamental hemodynamic mechanisms mediating the response to myocardial ischemia in conscious paraplegic mice: cardiac output versus peripheral resistance

Fundamental hemodynamic mechanisms mediating the response to myocardial ischemia in conscious paraplegic mice: cardiac output versus peripheral resistance

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

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

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