Chronic cardiac denervation affects the speed of coronary vascular regulation

Vergroesen, Isabelle; Merkus, Daphne; Teeffelen, Jurgen W. G. E. van; Dankelman, Jenny; Spaan, Jos A. E.; Wezel, Harry B. van; Noble, Mark I. M.; Drake-Holland, Angela J.

doi:10.1016/s0008-6363(99)00257-6

Cited by 12 publications

(6 citation statements)

References 28 publications

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“…We also confirmed a trend towards smaller infarcts in dogs subject to extracardiac nerve ablation or pharmacologic decentralization using the autonomic ganglionic blocker hexamethonium bromide (Figure 3) [106]; these findings are also in agreement with earlier studies documenting increased tolerance to ischemic injury and a reduction in ventricular fibrillation threshold post-decentralization [102,107,108]. Reduced oxygen demand and improved perfusion of affected tissues could be responsible for increased ischemic tolerance of myocytes [43,104,105,109] in the absence of intact cardiac nerves. Of note, extracardiac surgical ablation of sympathetic and parasympathetic efferent neuronal inputs produces a decentralized (not denervated) heart without complete elimination of parasympathetic involvement [110,111]; on the other hand, pharmacologic ganglionic blockade with hexamethonium bromide blocks transmission within peripheral autonomic ganglia and vagal cardio-acceleration [112].…”

Section: Heartsupporting

confidence: 91%

“…higher heart rate and LV systolic pressure) but stimulation with bradykinin produces a similar result without affecting LV pressure. On the other hand, Vergroesen et al documented that intact cardiac nerves were not essential for regulation of coronary blood flow [43]; however, they suggested that cardiac nerves essentially alter the speed of response of the coronary vascular bed to changes in heart rate and perfusion pressure. The cardiac nervous reflexes thought to be responsible for these effects has not been established but diverse cardiac afferent fibers and receptor subtypes (i.e.…”

Section: Vasoregulationmentioning

confidence: 99%

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Autonomic Nervous System and Neurocardiac Physiopathology

Kingma¹,

Simard²,

Rouleau³

2018

Autonomic Nervous System

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The autonomic nervous system regulates multiple physiological functions; how distinct neurons in peripheral autonomic and intrathoracic ganglia communicate remains to be established. Increasing focus is being paid to functionality of the neurocardiac axis and crosstalk between the intrinsic nervous system and diverse organ systems. Current findings indicate that progression of cardiovascular disease comprises peripheral and central aspects of the cardiac nervous system hierarchy. Indeed, autonomic neuronal dysfunction is known to participate in arrhythmogenesis and sudden cardiac death; diverse interventions (pharmacological, non-pharmacological) that affect neuronal remodeling in the heart following injury caused by cardiovascular disease (congestive heart failure, etc.) or acute myocardial infarction are being investigated. Herein we examine recent findings from clinical and animal studies on the role of the intrinsic cardiac nervous system on regulation of myocardial perfusion and the consequences of cardiac injury. We also discuss different interventions that target the autonomic nervous system, stimulate neuronal remodeling and adaptation, and thereby optimize patient outcomes.

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Section: Heartsupporting

confidence: 91%

Section: Vasoregulationmentioning

confidence: 99%

Autonomic Nervous System and Neurocardiac Physiopathology

Kingma¹,

Simard²,

Rouleau³

2018

Autonomic Nervous System

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“…In the Spaan studies a step change in coronary artery pressure resulted in autoregulation of flow that was described by a mathematical model that represented a dependence on pressure and oxygen consumption rate. Interestingly, Vergroesen et al (37) observed that the speed of coronary vascular regulation was slowed by cardiac denervation. The present simulation is based on steadystate measurements and provides no information on the speed of the response.…”

Section: Validation Of Predicted Autoregulatory Functionmentioning

confidence: 99%

Open-loop (feed-forward) and feedback control of coronary blood flow during exercise, cardiac pacing, and pressure changes

Pradhan

Feigl

Gorman

et al. 2016

American Journal of Physiology-Heart and Circulatory Physiology

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A control system model was developed to analyze data on in vivo coronary blood flow regulation and to probe how different mechanisms work together to control coronary flow from rest to exercise, and under a variety of experimental conditions, including cardiac pacing and with changes in coronary arterial pressure (autoregulation). In the model coronary flow is determined by the combined action of a feedback pathway signal that is determined by the level of plasma ATP in coronary venous blood, an adrenergic open-loop (feed-forward) signal that increases with exercise, and a contribution of pressure-mediated myogenic control. The model was identified based on data from exercise experiments where myocardial oxygen extraction, coronary flow, cardiac interstitial norepinephrine concentration, and arterial and coronary venous plasma ATP concentrations were measured during control and during adrenergic and purinergic receptor blockade conditions. The identified model was used to quantify the relative contributions of open-loop and feedback pathways and to illustrate the degree of redundancy in the control of coronary flow. The results indicate that the adrenergic open-loop control component is responsible for most of the increase in coronary blood flow that occurs during high levels of exercise. However, the adenine nucleotide-mediated metabolic feedback control component is essential. The model was evaluated by predicting coronary flow in cardiac pacing and autoregulation experiments with reasonable fits to the data. The analysis shows that a model in which coronary venous plasma adenine nucleotides are a signal in local metabolic feedback control of coronary flow is consistent with the available data.

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“…We also examined whether intact cardiac nerves were critical for coronary blood flow autoregulation; results confirmed a role for intrinsic cardiac neurons in autoregulatory control and myocardial perfusion even after ablation of extracardiac nerves from central nervous system control[26]. Ablation of external neuronal inputs to the heart also results in reduced myocardial efficiency that is consistent with impaired glucose utilization and depletion of cardiac catecholamine levels[27,28]; the latter directly affect myocardial oxygen demand[29-31]. Other animal studies reported that heterogeneity of myocardial perfusion is similar in innervated and denervated hearts[32-34]; possible explanations include: (1) the fact that regional denervation has little effect on vascular α-adrenergic receptors (in part due to circulating catecholamines); or (2) preserved neural modulation and autoregulation at different levels of the microcirculation across the ventricular wall[35,36].…”

Section: Coronary Blood Flow Regulation and Myocardial Perfusionmentioning

confidence: 94%

Influence of cardiac nerve status on cardiovascular regulation and cardioprotection

Kingma

Simard

Rouleau

2017

WJC

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Neural elements of the intrinsic cardiac nervous system transduce sensory inputs from the heart, blood vessels and other organs to ensure adequate cardiac function on a beat-to-beat basis. This inter-organ crosstalk is critical for normal function of the heart and other organs; derangements within the nervous system hierarchy contribute to pathogenesis of organ dysfunction. The role of intact cardiac nerves in development of, as well as protection against, ischemic injury is of current interest since it may involve recruitment of intrinsic cardiac ganglia. For instance, ischemic conditioning, a novel protection strategy against organ injury, and in particular remote conditioning, is likely mediated by activation of neural pathways or by endogenous cytoprotective blood-borne substances that stimulate different signalling pathways. This discovery reinforces the concept that inter-organ communication, and maintenance thereof, is key. As such, greater understanding of mechanisms and elucidation of treatment strategies is imperative to improve clinical outcomes particularly in patients with comorbidities. For instance, autonomic imbalance between sympathetic and parasympathetic nervous system regulation can initiate cardiovascular autonomic neuropathy that compromises cardiac stability and function. Neuromodulation therapies that directly target the intrinsic cardiac nervous system or other elements of the nervous system hierarchy are currently being investigated for treatment of different maladies in animal and human studies.

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Chronic cardiac denervation affects the speed of coronary vascular regulation

Cited by 12 publications

References 28 publications

Autonomic Nervous System and Neurocardiac Physiopathology

Autonomic Nervous System and Neurocardiac Physiopathology

Open-loop (feed-forward) and feedback control of coronary blood flow during exercise, cardiac pacing, and pressure changes

Influence of cardiac nerve status on cardiovascular regulation and cardioprotection

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