Influence of cigarette smoking on human autonomic function

NASA Technical Reports Server (NTRS)

Niedermaier, O. N.; Smith, M. L.; Beightol, L. A.; Zukowska-Grojec, Z.; Goldstein, D. S.; Eckberg, D. L.

1993-01-01

BACKGROUND. Although cigarette smoking is known to lead to widespread augmentation of sympathetic nervous system activity, little is known about the effects of smoking on directly measured human sympathetic activity and its reflex control. METHODS AND RESULTS. We studied the acute effects of smoking two research-grade cigarettes on muscle sympathetic nerve activity and on arterial baroreflex-mediated changes of sympathetic and vagal neural cardiovascular outflows in eight healthy habitual smokers. Measurements were made during frequency-controlled breathing, graded Valsalva maneuvers, and carotid baroreceptor stimulation with ramped sequences of neck pressure and suction. Smoking provoked the following changes: Arterial pressure increased significantly, and RR intervals, RR interval spectral power at the respiratory frequency, and muscle sympathetic nerve activity decreased. Plasma nicotine levels increased significantly, but plasma epinephrine, norepinephrine, and neuropeptide Y levels did not change. Peak sympathetic nerve activity during and systolic pressure overshoots after Valsalva straining increased significantly in proportion to increases of plasma nicotine levels. The average carotid baroreceptor-cardiac reflex relation shifted rightward and downward on arterial pressure and RR interval axes; average gain, operational point, and response range did not change. CONCLUSIONS. In habitual smokers, smoking acutely reduces baseline levels of vagal-cardiac nerve activity and completely resets vagally mediated arterial baroreceptor-cardiac reflex responses. Smoking also reduces muscle sympathetic nerve activity but augments increases of sympathetic activity triggered by brief arterial pressure reductions. This pattern of autonomic changes is likely to influence smokers' responses to acute arterial pressure reductions importantly.

New horizons in cardiac innervation imaging: introduction of novel 18F-labeled PET tracers.

PubMed

Kobayashi, Ryohei; Chen, Xinyu; Werner, Rudolf A; Lapa, Constantin; Javadi, Mehrbod S; Higuchi, Takahiro

2017-12-01

Cardiac sympathetic nervous activity can be uniquely visualized by non-invasive radionuclide imaging techniques due to the fast growing and widespread application of nuclear cardiology in the last few years. The norepinephrine analogue 123 I-meta-iodobenzylguanidine ( 123 I-MIBG) is a single photon emission computed tomography (SPECT) tracer for the clinical implementation of sympathetic nervous imaging for both diagnosis and prognosis of heart failure. Meanwhile, positron emission tomography (PET) imaging has become increasingly attractive because of its higher spatial and temporal resolution compared to SPECT, which allows regional functional and dynamic kinetic analysis. Nevertheless, wider use of cardiac sympathetic nervous PET imaging is still limited mainly due to the demand of costly on-site cyclotrons, which are required for the production of conventional 11 C-labeled (radiological half-life, 20 min) PET tracers. Most recently, more promising 18 F-labeled (half-life, 110 min) PET radiopharmaceuticals targeting sympathetic nervous system have been introduced. These tracers optimize PET imaging and, by using delivery networks, cost less to produce. In this article, the latest advances of sympathetic nervous imaging using 18 F-labeled radiotracers along with their possible applications are reviewed.

Effects of catheter-based renal denervation on cardiac sympathetic activity and innervation in patients with resistant hypertension.

PubMed

Donazzan, Luca; Mahfoud, Felix; Ewen, Sebastian; Ukena, Christian; Cremers, Bodo; Kirsch, Carl-Martin; Hellwig, Dirk; Eweiwi, Tareq; Ezziddin, Samer; Esler, Murray; Böhm, Michael

2016-04-01

To investigate, whether renal denervation (RDN) has a direct effect on cardiac sympathetic activity and innervation density. RDN demonstrated its efficacy not only in reducing blood pressure (BP) in certain patients, but also in decreasing cardiac hypertrophy and arrhythmias. These pleiotropic effects occur partly independent from the observed BP reduction. Eleven patients with resistant hypertension (mean office systolic BP 180 ± 18 mmHg, mean antihypertensive medications 6.0 ± 1.5) underwent I-123-mIBG scintigraphy to exclude pheochromocytoma. We measured cardiac sympathetic innervation and activity before and 9 months after RDN. Cardiac sympathetic innervation was assessed by heart to mediastinum ratio (H/M) and sympathetic activity by wash out ratio (WOR). Effects on office BP, 24 h ambulatory BP monitoring, were documented. Office systolic BP and mean ambulatory systolic BP were significantly reduced from 180 to 141 mmHg (p = 0.006) and from 149 to 129 mmHg (p = 0.014), respectively. Cardiac innervation remained unchanged before and after RDN (H/M 2.5 ± 0.5 versus 2.6 ± 0.4, p = 0.285). Cardiac sympathetic activity was significantly reduced by 67 % (WOR decreased from 24.1 ± 12.7 to 7.9 ± 25.3 %, p = 0.047). Both, responders and non-responders experienced a reduction of cardiac sympathetic activity. RDN significantly reduced cardiac sympathetic activity thereby demonstrating a direct effect on the heart. These changes occurred independently from BP effects and provide a pathophysiological basis for studies, investigating the potential effect of RDN on arrhythmias and heart failure.

Reflex effects on renal nerve activity characteristics in spontaneously hypertensive rats.

PubMed

DiBona, G F; Jones, S Y; Sawin, L L

1997-11-01

The effects of arterial and cardiac baroreflex activation on the discharge characteristics of renal sympathetic nerve activity were evaluated in conscious spontaneously hypertensive and Wistar-Kyoto rats. In spontaneously hypertensive rats compared with Wistar-Kyoto rats, (1) arterial baroreflex regulation of renal sympathetic nerve activity was reset to a higher arterial pressure and the gain was decreased and (2) cardiac baroreflex regulation of renal sympathetic nerve activity exhibited a lower gain. With the use of sympathetic peak detection analysis, the inhibition of integrated renal sympathetic nerve activity, which occurred during both increased arterial pressure (arterial baroreflex) and right atrial pressure (cardiac baroreflex), was due to parallel decreases in peak height with little change in peak frequency in both spontaneously hypertensive and Wistar-Kyoto rats. Arterial and cardiac baroreflex inhibition of renal sympathetic nerve activity in Wistar-Kyoto and spontaneously hypertensive rats is due to a parallel reduction in the number of active renal sympathetic nerve fibers.

Guilt and pride are heartfelt, but not equally so.

PubMed

Fourie, Melike M; Rauch, Henri G L; Morgan, Barak E; Ellis, George F R; Jordaan, Esmè R; Thomas, Kevin G F

2011-07-01

We examined the cardiovascular physiology of guilt and pride to elucidate physiological substrates underpinning the behavioral motivations of these moral emotions. Although both emotions motivate prosocial behavior, guilt typically inhibits ongoing behavior, whereas pride reinforces current behavior. To succeed in eliciting real emotions, we used a novel social interaction task. We found dissociable sympathetic activation during guilt and pride; specifically, Guilt participants experienced prolonged cardiac sympathetic arousal as measured by preejection period (PEP), whereas Pride participants experienced transient non-cardiac somatic arousal and a shift to low frequency (LF) power in the cardiac spectrogram. This dissociation supports their distinctive motivational functions. Higher self-reported Behavioral Inhibition System (BIS) sensitivity was furthermore uniquely associated with guilt, supporting its function as a punishment cue. Copyright © 2010 Society for Psychophysiological Research.

Effect of Switching from Cilnidipine to Azelnidipine on Cardiac Sympathetic Nerve Function in Patients with Heart Failure Preserved Ejection Fraction.

PubMed

Kiuchi, Shunsuke; Hisatake, Shinji; Kabuki, Takayuki; Oka, Takashi; Dobashi, Shintaro; Fujii, Takahiro; Ikeda, Takanori

2018-01-27

Cardiac sympathetic nerve activity is known to play a key role in the development and progression of heart failure (HF). Azelnidipine, an L-type calcium channel blocker (CCB), inhibits the sympathetic nerve activity of the central system. In contrast, cilnidipine, an N-type CCB, inhibits the sympathetic nerve activity of the peripheral system. CCBs are recommended as class IIa in patients with HF preserved ejection fraction (HFpEF); however, there are no comparative data on the difference in effect of cilnidipine and azelnidipine in patients with HFpEF and hypertension. We investigated the difference in effect of azelnidipine compared with cilnidipine in patients with HFpEF. Twenty-four consecutive HF patients who received angiotensin II type1a receptor blocker and beta blocker from April 2013 to January 2015 were enrolled. Cilnidipine was switched to azelnidipine during the follow-up period. Blood pressures, heart rate, blood tests, echocardiography, and 123 I-metaiodobenzylguanidine (MIBG) cardiac-scintigraphy were measured before and after 6 months from azelnidipine administration. B-type natriuretic peptide tended to decrease after switching to azelnidipine; however, there were no significant differences between the pre-state and post-state (pre-state: 118.5 pg/mL and post-state: 78.4 pg/mL, P = 0.137). Other laboratory findings, including catecholamine, also did not change significantly. In echocardiography, there were no significant differences in systolic and diastolic functions at the pre-state and post-state. As for MIBG, there were no significant changes in heart/mediastinum ratio. However, washout rate was significantly reduced (pre-state: 42.9 and post-state: 39.6, P = 0.030). Azelnidipine improved the dysfunction of cardiac sympathetic nerve activity compared with cilnidipine in patients with HFpEF.

Putting together the clues of the everlasting neuro-cardiac liaison.

PubMed

Franzoso, Mauro; Zaglia, Tania; Mongillo, Marco

2016-07-01

Starting from the late embryonic development, the sympathetic nervous system extensively innervates the heart and modulates its activity during the entire lifespan. The distribution of myocardial sympathetic processes is finely regulated by the secretion of limiting amounts of pro-survival neurotrophic factors by cardiac cells. Norepinephrine release by the neurons rapidly modulates myocardial electrophysiology, and increases the rate and force of cardiomyocyte contractions. Sympathetic processes establish direct interaction with cardiomyocytes, characterized by the presence of neurotransmitter vesicles and reduced cell-cell distance. Whether such contacts have a functional role in both neurotrophin- and catecholamine-dependent communication between the two cell types, is poorly understood. In this review we will address the effects of the sympathetic neuron activity on the myocardium and the hypothesis that the direct neuro-cardiac contact might have a key role both in norepinephrine and neurotrophin mediated signaling. This article is part of a Special Issue entitled: Cardiomyocyte Biology: Integration of Developmental and Environmental Cues in the Heart edited by Marcus Schaub and Hughes Abriel. Copyright © 2016 Elsevier B.V. All rights reserved.

Regulation of sympathetic nervous system function after cardiovascular deconditioning

NASA Technical Reports Server (NTRS)

Hasser, E. M.; Moffitt, J. A.

2001-01-01

Humans subjected to prolonged periods of bed rest or microgravity undergo deconditioning of the cardiovascular system, characterized by resting tachycardia, reduced exercise capability, and a predisposition for orthostatic intolerance. These changes in cardiovascular function are likely due to a combination of factors, including changes in control of body fluid balance or cardiac alterations resulting in inadequate maintenance of stroke volume, altered arterial or venous vascular function, reduced activation of cardiovascular hormones, and diminished autonomic reflex function. There is evidence indicating a role for each of these mechanisms. Diminished reflex activation of the sympathetic nervous system and subsequent vasoconstriction appear to play an important role. Studies utilizing the hindlimb-unloaded (HU) rat, an animal model of deconditioning, evaluated the potential role of altered arterial baroreflex control of the sympathetic nervous system. These studies indicate that HU results in blunted baroreflex-mediated activation of both renal and lumbar sympathetic nerve activity in response to a hypotensive stimulus. HU rats are less able to maintain arterial pressure during hemorrhage, suggesting that diminished ability to increase sympathetic activity has functional consequences for the animal. Reflex control of vasopressin secretion appears to be enhanced following HU. Blunted baroreflex-mediated sympathoexcitation appears to involve altered central nervous system function. Baroreceptor afferent activity in response to changes in arterial pressure is unaltered in HU rats. However, increases in efferent sympathetic nerve activity for a given decrease in afferent input are blunted after HU. This altered central nervous system processing of baroreceptor inputs appears to involve an effect at the rostral ventrolateral medulla (RVLM). Specifically, it appears that tonic GABAA-mediated inhibition of the RVLM is enhanced after HU. Augmented inhibition apparently arises from sources other than the caudal ventrolateral medulla. If similar alterations in control of the sympathetic nervous system occur in humans in response to cardiovascular deconditioning, it is likely that they play an important role in the observed tendency for orthostatic intolerance. Combined with potential changes in vascular function, cardiac function, and hypovolemia, the predisposition for orthostatic intolerance following cardiovascular deconditioning would be markedly enhanced by blunted ability to reflexly activate the sympathetic nervous system.

Non-motor symptoms and cardiac innervation in SYNJ1-related parkinsonism.

PubMed

De Rosa, A; Pellegrino, T; Pappatà, S; Lieto, M; Bonifati, V; Palma, V; Topa, A; Santoro, L; Bilo, L; Cuocolo, A; De Michele, G

2016-02-01

PARK20 is a rare autosomal recessive parkinsonism related to the SYNJ1 gene and characterized by early-onset of disease and atypical signs such as supranuclear vertical gaze palsy, dementia, dystonia, and generalized tonic-clonic seizures. Non-motor features and cardiac sympathetic innervation were assessed in two siblings affected by parkinsonism who harboured the homozygous Arg258Gln mutation in the SYNJ1 gene. The Non-Motor Symptoms, the SCOPA-AUT, the Mayo Sleep Questionnaires and polysomnography were used to investigate non-motor signs (NMS), autonomic dysfunction and REM Behavioural Disorder (RBD). Cognitive functions were examined by an extensive battery of neuropsychological tests. In addition, motor and sensory nerve conduction studies and evoked laser potentials were performed. Cardiac sympathetic innervation was assessed in the two patients by (123)I-metaiodobenzylguanidine (MIBG) scintigraphy, computing early and late heart-to-mediastinum (H/M) ratios and myocardial washout rates (WR). Among the non-motor symptoms and autonomic signs, case 1 had cold intolerance, drooling and dysphagia, while case 2 had pain and urinary dysfunction. Both cases showed mood and behavioural disorders. RBD were not found, whereas the neuropsychological assessment revealed a progressive cognitive impairment. Neurophysiological studies revealed no abnormalities. Indexes of cardiac sympathetic innervation in the two patients did not differ from those of control subjects. Our findings expand the phenotypic profile of SYNJ1-related parkinsonism. Preserved cardiac sympathetic function and absence of RBD suggest that PARK20 should be explained by a pathogenic mechanism different from Lewy Body pathology, or that the latter is not as widespread as idiopathic Parkinson's disease. Copyright © 2015 Elsevier Ltd. All rights reserved.

Rostral dorsolateral pontine neurons with sympathetic nerve-related activity.

PubMed

Barman, S M; Gebber, G L; Kitchens, H

1999-02-01

Spike-triggered averaging, arterial pulse-triggered analysis, and coherence analysis were used to classify rostral dorsolateral pontine (RDLP) neurons into groups whose naturally occurring discharges were correlated to only the 10-Hz rhythm (n = 29), to only the cardiac-related rhythm (n = 15), and to both rhythms (n = 15) in inferior cardiac sympathetic nerve discharge (SND) of urethan-anesthetized cats. Most of the neurons with activity correlated to only the cardiac-related rhythm were located medial to the other two groups of neurons. The firing rates of most RDLP neurons with activity correlated to only the 10-Hz rhythm (9 of 12) or both rhythms (7 of 8) were decreased during baroreceptor reflex-induced inhibition of SND produced by aortic obstruction; thus, they are presumed to be sympathoexcitatory. The firing rates of four of seven RDLP neurons with activity correlated to only the cardiac-related rhythm increased during baroreceptor reflex activation; thus, they may be sympathoinhibitory. We conclude that the RDLP contains a functionally heterogeneous population of neurons with sympathetic nerve-related activity. These neurons could not be antidromically activated by stimulation of the thoracic spinal cord.

Measures of Autonomic Nervous System Regulation

DTIC Science & Technology

2011-04-01

and most often used measures of ANS activation encompass non-invasive tools, which measure cardiac, skin conductance, respiratory , and vascular...regulation, osmotic balance, metabolism, digestion, excretion, and cardiac and respiratory activity. The ANS consists of the sympathetic and...modulate heart rate, as a function of the respiratory cycles. Generally, these two systems should be seen as permanently modulating vital functions to

Cholinergic Signaling Exerts Protective Effects in Models of Sympathetic Hyperactivity-Induced Cardiac Dysfunction

PubMed Central

Gavioli, Mariana; Lara, Aline; Almeida, Pedro W. M.; Lima, Augusto Martins; Damasceno, Denis D.; Rocha-Resende, Cibele; Ladeira, Marina; Resende, Rodrigo R.; Martinelli, Patricia M.; Melo, Marcos Barrouin; Brum, Patricia C.; Fontes, Marco Antonio Peliky; Souza Santos, Robson A.; Prado, Marco A. M.; Guatimosim, Silvia

2014-01-01

Cholinergic control of the heart is exerted by two distinct branches; the autonomic component represented by the parasympathetic nervous system, and the recently described non-neuronal cardiomyocyte cholinergic machinery. Previous evidence has shown that reduced cholinergic function leads to deleterious effects on the myocardium. Yet, whether conditions of increased cholinergic signaling can offset the pathological remodeling induced by sympathetic hyperactivity, and its consequences for these two cholinergic axes are unknown. Here, we investigated two models of sympathetic hyperactivity: i) the chronic beta-adrenergic receptor stimulation evoked by isoproterenol (ISO), and ii) the α2A/α2C-adrenergic receptor knockout (KO) mice that lack pre-synaptic adrenergic receptors. In both models, cholinergic signaling was increased by administration of the cholinesterase inhibitor, pyridostigmine. First, we observed that isoproterenol produces an autonomic imbalance characterized by increased sympathetic and reduced parasympathetic tone. Under this condition transcripts for cholinergic proteins were upregulated in ventricular myocytes, indicating that non-neuronal cholinergic machinery is activated during adrenergic overdrive. Pyridostigmine treatment prevented the effects of ISO on autonomic function and on the ventricular cholinergic machinery, and inhibited cardiac remodeling. α2A/α2C-KO mice presented reduced ventricular contraction when compared to wild-type mice, and this dysfunction was also reversed by cholinesterase inhibition. Thus, the cardiac parasympathetic system and non-neuronal cardiomyocyte cholinergic machinery are modulated in opposite directions under conditions of increased sympathetic drive or ACh availability. Moreover, our data support the idea that pyridostigmine by restoring ACh availability is beneficial in heart disease. PMID:24992197

Chronic orthostatic intolerance: a disorder with discordant cardiac and vascular sympathetic control

NASA Technical Reports Server (NTRS)

Furlan, R.; Jacob, G.; Snell, M.; Robertson, D.; Porta, A.; Harris, P.; Mosqueda-Garcia, R.

1998-01-01

BACKGROUND: Chronic orthostatic intolerance (COI) is a debilitating autonomic condition in young adults. Its neurohumoral and hemodynamic profiles suggest possible alterations of postural sympathetic function and of baroreflex control of heart rate (HR). METHODS AND RESULTS: In 16 COI patients and 16 healthy volunteers, intra-arterial blood pressure (BP), ECG, central venous pressure (CVP), and muscle sympathetic nerve activity (MSNA) were recorded at rest and during 75 degrees tilt. Spectral analysis of RR interval and systolic arterial pressure (SAP) variabilities provided indices of sympathovagal modulation of the sinoatrial node (ratio of low-frequency to high-frequency components, LF/HF) and of sympathetic vasomotor control (LFSAP). Baroreflex mechanisms were assessed (1) by the slope of the regression line obtained from changes of RR interval and MSNA evoked by pharmacologically induced alterations in BP and (2) by the index alpha, obtained from cross-spectral analysis of RR and SAP variabilities. At rest, HR, MSNA, LF/HF, and LFSAP were higher in COI patients, whereas BP and CVP were similar in the two groups. During tilt, BP did not change and CVP fell by the same extent in the 2 groups; the increase of HR and LF/HF was more pronounced in COI patients. Conversely, the increase of MSNA was lower in COI than in control subjects. Baroreflex sensitivity was similar in COI and control subjects at rest; tilt reduced alpha similarly in both groups. CONCLUSIONS: COI is characterized by an overall enhancement of noradrenergic tone at rest and by a blunted postganglionic sympathetic response to standing, with a compensatory cardiac sympathetic overactivity. Baroreflex mechanisms maintain their functional responsiveness. These data suggest that in COI, the functional distribution of central sympathetic tone to the heart and vasculature is abnormal.

Effects of Spinal Cord Stimulation on Cardiac Sympathetic Nerve Activity in Patients with Heart Failure.

PubMed

Naar, Jan; Jaye, Deborah; Linde, Cecilia; Neužil, Petr; Doškář, Petr; Málek, Filip; Braunschweig, Frieder; Lund, Lars H; Mortensen, Lars; Linderoth, Bengt; Lind, Göran; Bone, Dianna; Scholte, Arthur J; Kueffer, Fred; Koehler, Jodi; Shahgaldi, Kambiz; Lang, Otto; Ståhlberg, Marcus

2017-05-01

Spinal cord stimulation (SCS) reduces sympathetic activity in animal models of heart failure with reduced ejection fraction (HF) but limited data exist of SCS in patients with HF. The aim of the present study was to test the primary hypothesis that SCS reduces cardiac sympathetic nerve activity in HF patients. Secondary hypotheses were that SCS improves left ventricular function and dimension, exercise capacity, and clinical variables relevant to HF. HF patients with a SCS device previously participating in the DEFEAT-HF trial were included in this crossover study with 6-week intervention periods (SCS-ON and SCS-OFF). SCS (50 Hz, 210-μs pulse duration, aiming at T2-T4 segments) was delivered for 12 hours daily. Indices of myocardial sympathetic neuronal function (heart-to-mediastinum ratio, HMR) and activity (washout rate, WR) were assessed using 123 I-metaiodobenzylguanidine (MIBG) scintigraphy. Echocardiography, exercise testing, and clinical data collection were also performed. We included 13 patients (65.3 ± 8.0 years, nine males) and MIBG scintigraphy data were available in 10. HMR was not different comparing SCS-ON (1.37 ± 0.16) and SCS-OFF (1.41 ± 0.21, P = 0.46). WR was also unchanged comparing SCS-ON (41.5 ± 5.3) and SCS-OFF (39.1 ± 5.8, P = 0.30). Similarly, average New York Heart Association class (2.4 ± 0.5 vs 2.3 ± 0.6, P = 0.34), quality of life score (24 ± 16 vs 24 ± 16, P = 0.94), and left ventricular dimension and function as well as exercise capacity were all unchanged comparing SCS-ON and SCS-OFF. In patients with HF, SCS (12 hours daily, targeting the T2-T4 segments of the spinal cord) does not appear to influence cardiac sympathetic neuronal activity or function as assessed by MIBG scintigraphy. © 2017 Wiley Periodicals, Inc.

Autonomic Cardiovascular Control and Executive Function in Chronic Hypotension.

PubMed

Duschek, Stefan; Hoffmann, Alexandra; Reyes Del Paso, Gustavo A; Ettinger, Ulrich

2017-06-01

Chronic low blood pressure (hypotension) is characterized by complaints such as fatigue, reduced drive, dizziness, and cold limbs. Additionally, deficits in attention and memory have been observed. Autonomic dysregulation is considered to be involved in the origin of this condition. The study explored autonomic cardiovascular control in the context of higher cognitive processing (executive function) in hypotension. Hemodynamic recordings were performed in 40 hypotensive and 40 normotensive participants during execution of four classical executive function tasks (number-letter task, n-back task, continuous performance test, and flanker task). Parameters of cardiac sympathetic control, i.e., stroke volume, cardiac output, pre-ejection period, total peripheral resistance, and parasympathetic control, i.e., respiratory sinus arrhythmia and baroreflex sensitivity, were obtained. The hypotensive group exhibited lower stroke volume and cardiac output, as well as higher pre-ejection period and baroreflex sensitivity during task execution. Increased error rates in hypotensive individuals were observed in the n-back and flanker tasks. In the total sample, there were positive correlations of error rates with pre-ejection period, baroreflex sensitivity and respiratory sinus arrhythmia, and negative correlations with cardiac output. Group differences in stroke volume, cardiac output, and pre-ejection period suggest diminished beta-adrenergic myocardial drive during executive function processing in hypotension, in addition to increased baroreflex function. Although further research is warranted to quantify the extent of executive function impairment in hypotension, the results from correlation analysis add evidence to the notion that higher sympathetic inotropic influences and reduced parasympathetic cardiac influences are accompanied by better cognitive performance.

Pressor response to intravenous tyramine is a marker of cardiac, but not vascular, adrenergic function

NASA Technical Reports Server (NTRS)

Meck, Janice V.; Martin, David S.; D'Aunno, Dominick S.; Waters, Wendy W.

2003-01-01

Intravenous injections of the indirect sympathetic amine, tyramine, are used as a test of peripheral adrenergic function. The authors measured the time course of increases in ejection fraction, heart rate, systolic and diastolic pressure, popliteal artery flow, and greater saphenous vein diameter before and after an injection of 4.0 mg/m(2) body surface area of tyramine in normal human subjects. The tyramine caused moderate, significant increases in systolic pressure and significant decreases in total peripheral resistance. The earliest changes were a 30% increase in ejection fraction and a 16% increase in systolic pressure, followed by a 60% increase in popliteal artery flow and a later 11% increase in greater saphenous vein diameter. There were no changes in diastolic pressure or heart rate. These results suggest that pressor responses during tyramine injections are primarily due to an inotropic response that increases cardiac output and pressure and causes a reflex decrease in vascular resistance. Thus, tyramine pressor tests are a measure of cardiac, but not vascular, sympathetic function.

Heart rate complexity: A novel approach to assessing cardiac stress reactivity.

PubMed

Brindle, Ryan C; Ginty, Annie T; Phillips, Anna C; Fisher, James P; McIntyre, David; Carroll, Douglas

2016-04-01

Correlation dimension (D2), a measure of heart rate (HR) complexity, has been shown to decrease in response to acute mental stress and relate to adverse cardiovascular health. However, the relationship between stress-induced changes in D2 and HR has yet to be established. The present studies aimed to assess this relationship systematically while controlling for changes in respiration and autonomic activity. In Study 1 (N = 25) D2 decreased during stress and predicted HR reactivity even after adjusting for changes in respiration rate, and cardiac vagal tone. This result was replicated in Study 2 (N = 162) and extended by including a measure of cardiac sympathetic activity; correlation dimension remained an independent predictor of HR reactivity in a hierarchical linear model containing measures of cardiac parasympathetic and sympathetic activity and their interaction. These results suggest that correlation dimension may provide additional information regarding cardiac stress reactivity above that provided by traditional measures of cardiac autonomic function. © 2015 Society for Psychophysiological Research.

Assessment of cardiac sympathetic neuronal function using PET imaging.

PubMed

Bengel, Frank M; Schwaiger, Markus

2004-01-01

The autonomic nervous system plays a key role for regulation of cardiac performance, and the importance of alterations of innervation in the pathophysiology of various heart diseases has been increasingly emphasized. Nuclear imaging techniques have been established that allow for global and regional investigation of the myocardial nervous system. The guanethidine analog iodine 123 metaiodobenzylguanidine (MIBG) has been introduced for scintigraphic mapping of presynaptic sympathetic innervation and is available today for imaging on a broad clinical basis. Not much later than MIBG, positron emission tomography (PET) has also been established for characterizing the cardiac autonomic nervous system. Although PET is methodologically demanding and less widely available, it provides substantial advantages. High spatial and temporal resolution along with routinely available attenuation correction allows for detailed definition of tracer kinetics and makes noninvasive absolute quantification a reality. Furthermore, a series of different radiolabeled catecholamines, catecholamine analogs, and receptor ligands are available. Those are often more physiologic than MIBG and well understood with regard to their tracer physiologic properties. PET imaging of sympathetic neuronal function has been successfully applied to gain mechanistic insights into myocardial biology and pathology. Available tracers allow dissection of processes of presynaptic and postsynaptic innervation contributing to cardiovascular disease. This review summarizes characteristics of currently available PET tracers for cardiac neuroimaging along with the major findings derived from their application in health and disease.

The articulo-cardiac sympathetic reflex in spinalized, anesthetized rats.

PubMed

Nakayama, Tomohiro; Suzuki, Atsuko; Ito, Ryuzo

2006-04-01

Somatic afferent regulation of heart rate by noxious knee joint stimulation has been proven in anesthetized cats to be a reflex response whose reflex center is in the brain and whose efferent arc is a cardiac sympathetic nerve. In the present study we examined whether articular stimulation could influence heart rate by this efferent sympathetic pathway in spinalized rats. In central nervous system (CNS)-intact rats, noxious articular movement of either the knee or elbow joint resulted in an increase in cardiac sympathetic nerve activity and heart rate. However, although in acutely spinalized rats a noxious movement of the elbow joint resulted in a significant increase in cardiac sympathetic nerve activity and heart rate, a noxious movement of the knee joint had no such effect and resulted in only a marginal increase in heart rate. Because this marginal increase was abolished by adrenalectomy suggests that it was due to the release of adrenal catecholamines. In conclusion, the spinal cord appears to be capable of mediating, by way of cardiac sympathetic nerves, the propriospinally induced reflex increase in heart rate that follows noxious stimulation of the elbow joint, but not the knee joint.

Effect of endogenous angiotensin II on renal nerve activity and its cardiac baroreflex regulation.

PubMed

Dibona, G F; Jones, S Y; Sawin, L L

1998-11-01

The effects of physiologic alterations in endogenous angiotensin II activity on basal renal sympathetic nerve activity and its cardiac baroreflex regulation were studied. The effect of angiotensin II type 1 receptor blockade with intracerebroventricular losartan was examined in conscious rats consuming a low, normal, or high sodium diet that were instrumented for the simultaneous measurement of right atrial pressure and renal sympathetic nerve activity. The gain of cardiac baroreflex regulation of renal sympathetic nerve activity (% delta renal sympathetic nerve activity/mmHg mean right atrial pressure) was measured during isotonic saline volume loading. Intracerebroventricular losartan did not decrease arterial pressure but significantly decreased renal sympathetic nerve activity in low (-36+/-6%) and normal (-24+/-5%), but not in high (-2+/-3%) sodium diet rats. Compared with vehicle treatment, losartan treatment significantly increased cardiac baroreflex gain in low (-3.45+/-0.20 versus -2.89+/-0.17) and normal (-2.89+/-0.18 versus -2.54+/-0.14), but not in high (-2.27+/-0.15 versus -2.22+/-0.14) sodium diet rats. These results indicate that physiologic alterations in endogenous angiotensin II activity tonically influence basal levels of renal sympathetic nerve activity and its cardiac baroreflex regulation.

Central command: control of cardiac sympathetic and vagal efferent nerve activity and the arterial baroreflex during spontaneous motor behaviour in animals.

PubMed

Matsukawa, Kanji

2012-01-01

Feedforward control by higher brain centres (termed central command) plays a role in the autonomic regulation of the cardiovascular system during exercise. Over the past 20 years, workers in our laboratory have used the precollicular-premammillary decerebrate animal model to identify the neural circuitry involved in the CNS control of cardiac autonomic outflow and arterial baroreflex function. Contrary to the traditional idea that vagal withdrawal at the onset of exercise causes the increase in heart rate, central command did not decrease cardiac vagal efferent nerve activity but did allow cardiac sympathetic efferent nerve activity to produce cardiac acceleration. In addition, central command-evoked inhibition of the aortic baroreceptor-heart rate reflex blunted the baroreflex-mediated bradycardia elicited by aortic nerve stimulation, further increasing the heart rate at the onset of exercise. Spontaneous motor activity and associated cardiovascular responses disappeared in animals decerebrated at the midcollicular level. These findings indicate that the brain region including the caudal diencephalon and extending to the rostral mesencephalon may play a role in generating central command. Bicuculline microinjected into the midbrain ventral tegmental area of decerebrate rats produced a long-lasting repetitive activation of renal sympathetic nerve activity that was synchronized with the motor nerve discharge. When lidocaine was microinjected into the ventral tegmental area, the spontaneous motor activity and associated cardiovascular responses ceased. From these findings, we conclude that cerebral cortical outputs trigger activation of neural circuits within the caudal brain, including the ventral tegmental area, which causes central command to augment cardiac sympathetic outflow at the onset of exercise in decerebrate animal models.

Contemporary review on the pathogenesis of takotsubo syndrome: The heart shedding tears: Norepinephrine churn and foam at the cardiac sympathetic nerve terminals.

PubMed

Y-Hassan, Shams; De Palma, Rodney

2017-02-01

Takotsubo syndrome (TS), an increasingly recognized acute cardiac disease entity, is characterized by a unique pattern of circumferential and typically regional left ventricular wall motion abnormality resulting in a conspicuous transient ballooning of the left ventricle during systole. The mechanism of the disease remains elusive. However, the sudden onset of acute myocardial stunning in a systematic pattern extending beyond a coronary artery territory; the history of a preceding emotional or physical stress factor in two thirds of cases; the signs of sympathetic denervation at the regions of left ventricular dysfunction on sympathetic scintigraphy; the finding of myocardial edema and other signs consistent with (catecholamine-induced) myocarditis shown by cardiac magnetic resonance imaging; and the contraction band necrosis on histopathological examination all argue strongly for the involvement of the cardiac sympathetic nervous system in the pathogenesis of TS. In this narrative review, extensive evidence in support of local cardiac sympathetic nerve hyperactivation, disruption and norepinephrine spillover causing TS in predisposed patients is provided. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Higher sympathetic nerve activity during ventricular (VVI) than during dual-chamber (DDD) pacing

NASA Technical Reports Server (NTRS)

Taylor, J. A.; Morillo, C. A.; Eckberg, D. L.; Ellenbogen, K. A.

1996-01-01

OBJECTIVES: We determined the short-term effects of single-chamber ventricular pacing and dual-chamber atrioventricular (AV) pacing on directly measured sympathetic nerve activity. BACKGROUND: Dual-chamber AV cardiac pacing results in greater cardiac output and lower systemic vascular resistance than does single-chamber ventricular pacing. However, it is unclear whether these hemodynamic advantages result in less sympathetic nervous system outflow. METHODS: In 13 patients with a dual-chamber pacemaker, we recorded the electrocardiogram, noninvasive arterial pressure (Finapres), respiration and muscle sympathetic nerve activity (microneurography) during 3 min of underlying basal heart rate and 3 min of ventricular and AV pacing at rates of 60 and 100 beats/min. RESULTS: Arterial pressure was lowest and muscle sympathetic nerve activity was highest at the underlying basal heart rate. Arterial pressure increased with cardiac pacing and was greater with AV than with ventricular pacing (change in mean blood pressure +/- SE: 10 +/- 3 vs. 2 +/- 2 mm Hg at 60 beats/min; 21 +/- 5 vs. 14 +/- 2 mm Hg at 100 beats/min; p < 0.05). Sympathetic nerve activity decreased with cardiac pacing and the decline was greater with AV than with ventricular pacing (60 beats/min -40 +/- 11% vs. -17 +/- 7%; 100 beats/min -60 +/- 9% vs. -48 +/- 10%; p < 0.05). Although most patients showed a strong inverse relation between arterial pressure and muscle sympathetic nerve activity, three patients with severe left ventricular dysfunction (ejection fraction < or = 30%) showed no relation between arterial pressure and sympathetic activity. CONCLUSIONS: Short-term AV pacing results in lower sympathetic nerve activity and higher arterial pressure than does ventricular pacing, indicating that cardiac pacing mode may influence sympathetic outflow simply through arterial baroreflex mechanisms. We speculate that the greater incidence of adverse outcomes in patients treated with single-chamber ventricular rather than dual-chamber pacing may be due in part to increased sympathetic nervous outflow.

Cardiac-locked bursts of muscle sympathetic nerve activity are absent in familial dysautonomia

PubMed Central

Macefield, Vaughan G; Norcliffe-Kaufmann, Lucy; Axelrod, Felicia B; Kaufmann, Horacio

2013-01-01

Familial dysautonomia (Riley–Day syndrome) is an hereditary sensory and autonomic neuropathy (HSAN type III), expressed at birth, that is associated with reduced pain and temperature sensibilities and absent baroreflexes, causing orthostatic hypotension as well as labile blood pressure that increases markedly during emotional excitement. Given the apparent absence of functional baroreceptor afferents, we tested the hypothesis that the normal cardiac-locked bursts of muscle sympathetic nerve activity (MSNA) are absent in patients with familial dysautonomia. Tungsten microelectrodes were inserted percutaneously into muscle or cutaneous fascicles of the common peroneal nerve in 12 patients with familial dysautonomia. Spontaneous bursts of MSNA were absent in all patients, but in five patients we found evidence of tonically firing sympathetic neurones, with no cardiac rhythmicity, that increased their spontaneous discharge during emotional arousal but not during a manoeuvre that unloads the baroreceptors. Conversely, skin sympathetic nerve activity (SSNA), recorded in four patients, appeared normal. We conclude that the loss of phasic bursts of MSNA and the loss of baroreflex modulation of muscle vasoconstrictor drive contributes to the poor control of blood pressure in familial dysautonomia, and that the increase in tonic firing of muscle vasoconstrictor neurones contributes to the increase in blood pressure during emotional excitement. PMID:23165765

Role of the renin-angiotensin system in cardiac hypertrophy induced in rats by hyperthyroidism

PubMed Central

KOBORI, HIROYUKI; ICHIHARA, ATSUHIRO; SUZUKI, HIROMICHI; TAKENAKA, TSUNEO; MIYASHITA, YUTAKA; HAYASHI, MATSUHIKO; SARUTA, TAKAO

2008-01-01

This study was conducted to examine whether the renin-angiotensin system contributes to hyperthyroidism-induced cardiac hypertrophy without involving the sympathetic nervous system. Sprague-Dawley rats were divided into control-innervated, control-denervated, hyperthyroid-innervated, and hyperthyroid-denervated groups using intraperitoneal injections of thyroxine and 6-hydroxydopamine. After 8 wk, the heart-to-body weight ratio increased in hyperthyroid groups (63%), and this increase was only partially inhibited by sympathetic denervation. Radioimmunoassays and reverse transcription-polymerase chain reaction revealed increased cardiac levels of renin (33%) and angiotensin II (53%) and enhanced cardiac expression of renin mRNA (225%) in the hyperthyroid groups. These increases were unaffected by sympathetic denervation or 24-h bilateral nephrectomy. In addition, losartan and nicardipine decreased systolic blood pressure to the same extent, but only losartan caused regression of thyroxine-induced cardiac hypertrophy. These results suggest that thyroid hormone activates the cardiac renin-angiotensin system without involving the sympathetic nervous system or the circulating renin-angiotensin system; the activated renin-angiotensin system contributes to cardiac hypertrophy in hyperthyroidism. PMID:9277473

Role of the renin-angiotensin system in cardiac hypertrophy induced in rats by hyperthyroidism.

PubMed

Kobori, H; Ichihara, A; Suzuki, H; Takenaka, T; Miyashita, Y; Hayashi, M; Saruta, T

1997-08-01

This study was conducted to examine whether the renin-angiotensin system contributes to hyperthyroidism-induced cardiac hypertrophy without involving the sympathetic nervous system. Sprague-Dawley rats were divided into control-innervated, control-denervated, hyperthyroid-innervated, and hyperthyroid-denervated groups using intraperitoneal injections of thyroxine and 6-hydroxydopamine. After 8 wk, the heart-to-body weight ratio increased in hyperthyroid groups (63%), and this increase was only partially inhibited by sympathetic denervation. Radioimmunoassays and reverse transcription-polymerase chain reaction revealed increased cardiac levels of renin (33%) and angiotensin II (53%) and enhanced cardiac expression of renin mRNA (225%) in the hyperthyroid groups. These increases were unaffected by sympathetic denervation or 24-h bilateral nephrectomy. In addition, losartan and nicardipine decreased systolic blood pressure to the same extent, but only losartan caused regression of thyroxine-induced cardiac hypertrophy. These results suggest that thyroid hormone activates the cardiac renin-angiotensin system without involving the sympathetic nervous system or the circulating renin-angiotensin system; the activated renin-angiotensin system contributes to cardiac hypertrophy in hyperthyroidism.

The plasminogen activator system modulates sympathetic nerve function.

PubMed

Schaefer, Ulrich; Machida, Takuji; Vorlova, Sandra; Strickland, Sidney; Levi, Roberto

2006-09-04

Sympathetic neurons synthesize and release tissue plasminogen activator (t-PA). We investigated whether t-PA modulates sympathetic activity. t-PA inhibition markedly reduced contraction of the guinea pig vas deferens to electrical field stimulation (EFS) and norepinephrine (NE) exocytosis from cardiac synaptosomes. Recombinant t-PA (rt-PA) induced exocytotic and carrier-mediated NE release from cardiac synaptosomes and cultured neuroblastoma cells; this was a plasmin-independent effect but was potentiated by a fibrinogen cleavage product. Notably, hearts from t-PA-null mice released much less NE upon EFS than their wild-type (WT) controls (i.e., a 76.5% decrease; P<0.01), whereas hearts from plasminogen activator inhibitor-1 (PAI-1)-null mice released much more NE (i.e., a 275% increase; P<0.05). Furthermore, vasa deferentia from t-PA-null mice were hyporesponsive to EFS (P<0.0001) but were normalized by the addition of rt-PA. In contrast, vasa from PAI-1-null mice were much more responsive (P<0.05). Coronary NE overflow from hearts subjected to ischemia/reperfusion was much smaller in t-PA-null than in WT control mice (P<0.01). Furthermore, reperfusion arrhythmias were significantly reduced (P<0.05) in t-PA-null hearts. Thus, t-PA enhances NE release from sympathetic nerves and contributes to cardiac arrhythmias in ischemia/reperfusion. Because the risk of arrhythmias and sudden cardiac death is increased in hyperadrenergic conditions, targeting the NE-releasing effect of t-PA may have valuable therapeutic potential.

Dietary restriction, cardiac autonomic regulation and stress reactivity in bulimic women.

PubMed

Vögele, Claus; Hilbert, Anja; Tuschen-Caffier, Brunna

2009-08-04

Recent findings suggest sympathetic inhibition during dietary restriction as opposed to increased sympathetic activity during re-feeding. The present study investigated cardiac autonomic regulation and stress reactivity in relation to biochemical markers of dietary restriction status in women diagnosed with bulimia nervosa. We predicted that bulimic individuals (BN) with a biochemical profile indicating dietary restriction exhibit reduced cardiac sympathetic and/or increased vagal activity. We also hypothesized, that BN with a biochemical profile within a normal range (i.e. currently not dieting or malnourished) would show heart rate variability responses (HRV) and reactivity to mental stress indicating increased sympathetic activation compared with non-eating disordered controls. Seventeen female volunteers diagnosed with bulimia nervosa were categorized according to their serum profile (glucose, pre-albumin, IGF-1, TSH, leptin) into currently fasting versus non-fasting and compared with 16 non-eating disordered controls matched for age and BMI. Spectral components of HRV were calculated on heart rate data from resting and mental stress periods (standardized achievement challenge) using autoregressive analysis. Compared to non-fasting BN and controls, fasting BN showed increased vagal and decreased sympathetic modulation during both resting and recovery periods. Cardiac autonomic regulation was not impaired in response to mental challenge. No differences could be found between non-fasting BN and controls. The results confirm the notion of cardiac sympathetic inhibition and vagal dominance during dietary restriction and suggest the specificity of starvation related biochemical changes for cardiac autonomic control. The results are discussed in terms of the higher incidence in cardiac complications in these patients.

Measures of Autonomic Nervous System

DTIC Science & Technology

2011-04-01

activation encompass non-invasive tools, which measure cardiac, skin conductance, respiratory , and vascular activity. Choice of tools is dependent upon...digestion, excretion, and cardiac and respiratory activity. The ANS consists of the sympathetic and parasympathetic divisions and acts through a... respiratory cycles. Generally, these two systems should be seen as permanently modulating vital functions to achieve homeostasis. Since both systems are

Single-unit muscle sympathetic nervous activity and its relation to cardiac noradrenaline spillover

PubMed Central

Lambert, Elisabeth A; Schlaich, Markus P; Dawood, Tye; Sari, Carolina; Chopra, Reena; Barton, David A; Kaye, David M; Elam, Mikael; Esler, Murray D; Lambert, Gavin W

2011-01-01

Abstract Recent work using single-unit sympathetic nerve recording techniques has demonstrated aberrations in the firing pattern of sympathetic nerves in a variety of patient groups. We sought to examine whether nerve firing pattern is associated with increased noradrenaline release. Using single-unit muscle sympathetic nerve recording techniques coupled with direct cardiac catheterisation and noradrenaline isotope dilution methodology we examined the relationship between single-unit firing patterns and cardiac and whole body noradrenaline spillover to plasma. Participants comprised patients with hypertension (n = 6), depression (n = 7) and panic disorder (n = 9) who were drawn from our ongoing studies. The patient groups examined did not differ in their single-unit muscle sympathetic nerve firing characteristics nor in the rate of spillover of noradrenaline to plasma from the heart. The median incidence of multiple spikes per beat was 9%. Patients were stratified according to the firing pattern: low level of incidence (less than 9% incidence of multiple spikes per beat) and high level of incidence (greater than 9% incidence of multiple spikes per beat). High incidence of multiple spikes within a cardiac cycle was associated with higher firing rates (P < 0.0001) and increased probability of firing (P < 0.0001). Whole body noradrenaline spillover to plasma and (multi-unit) muscle sympathetic nerve activity in subjects with low incidence of multiple spikes was not different to that of those with high incidence of multiple spikes. In those with high incidence of multiple spikes there occurred a parallel activation of the sympathetic outflow to the heart, with cardiac noradrenaline spillover to plasma being two times that of subjects with low nerve firing rates (11.0 ± 1.5 vs. 22.0 ± 4.5 ng min−1, P < 0.05). This study indicates that multiple within-burst firing and increased single-unit firing rates of the sympathetic outflow to the skeletal muscle vasculature is associated with high cardiac noradrenaline spillover. PMID:21486790

Magnitude of Morning Surge in Blood Pressure Is Associated with Sympathetic but Not Cardiac Baroreflex Sensitivity

PubMed Central

Johnson, Aaron W.; Hissen, Sarah L.; Macefield, Vaughan G.; Brown, Rachael; Taylor, Chloe E.

2016-01-01

The ability of the arterial baroreflex to regulate blood pressure may influence the magnitude of the morning surge in blood pressure (MSBP). The aim was to investigate the relationships between sympathetic and cardiac baroreflex sensitivity (BRS) and the morning surge. Twenty-four hour ambulatory blood pressure was recorded in 14 young individuals. The morning surge was defined via the pre-awakening method, which is calculated as the difference between mean blood pressure values 2 h before and 2 h after rising from sleep. The mean systolic morning surge, diastolic morning surge, and morning surge in mean arterial pressures were 15 ± 2, 13 ± 1, and 11 ± 1 mmHg, respectively. During the laboratory protocol, continuous measurements of blood pressure, heart rate, and muscle sympathetic nerve activity (MSNA) were made over a 10-min period of rest. Sympathetic BRS was quantified by plotting MSNA burst incidence against diastolic pressure (sympathetic BRSinc), and by plotting total MSNA against diastolic pressure (sympathetic BRStotal). Cardiac BRS was quantified using the sequence method. The mean values for sympathetic BRSinc, sympathetic BRStotal and cardiac BRS were −1.26 ± 0.26 bursts/100 hb/mmHg, −1.60 ± 0.37 AU/beat/mmHg, and 13.1 ± 1.5 ms/mmHg respectively. Significant relationships were identified between sympathetic BRSinc and the diastolic morning surge (r = 0.62, p = 0.02) and the morning surge in mean arterial pressure (r = 0.57, p = 0.03). Low sympathetic BRS was associated with a larger morning surge in mean arterial and diastolic blood pressure. Trends for relationships were identified between sympathetic BRStotal and the diastolic morning surge (r = 0.52, p = 0.066) and the morning surge in mean arterial pressure (r = 0.48, p = 0.095) but these did not reach significance. There were no significant relationships between cardiac BRS and the morning surge. These findings indicate that the ability of the baroreflex to buffer increases in blood pressure via reflexive changes in MSNA may play a role in determining the magnitude of the MSBP. PMID:27660603

Functional role of peripheral opioid receptors in the regulation of cardiac spinal afferent nerve activity during myocardial ischemia

PubMed Central

Longhurst, John C.

2013-01-01

Thinly myelinated Aδ-fiber and unmyelinated C-fiber cardiac sympathetic (spinal) sensory nerve fibers are activated during myocardial ischemia to transmit the sensation of angina pectoris. Although recent observations showed that myocardial ischemia increases the concentrations of opioid peptides and that the stimulation of peripheral opioid receptors inhibits chemically induced visceral and somatic nociception, the role of opioids in cardiac spinal afferent signaling during myocardial ischemia has not been studied. The present study tested the hypothesis that peripheral opioid receptors modulate cardiac spinal afferent nerve activity during myocardial ischemia by suppressing the responses of cardiac afferent nerve to ischemic mediators like bradykinin and extracellular ATP. The nerve activity of single unit cardiac afferents was recorded from the left sympathetic chain (T2–T5) in anesthetized cats. Forty-three ischemically sensitive afferent nerves (conduction velocity: 0.32–3.90 m/s) with receptive fields in the left and right ventricles were identified. The responses of these afferent nerves to repeat ischemia or ischemic mediators were further studied in the following protocols. First, epicardial administration of naloxone (8 μmol), a nonselective opioid receptor antagonist, enhanced the responses of eight cardiac afferent nerves to recurrent myocardial ischemia by 62%, whereas epicardial application of vehicle (PBS) did not alter the responses of seven other cardiac afferent nerves to ischemia. Second, naloxone applied to the epicardial surface facilitated the responses of seven cardiac afferent nerves to epicardial ATP by 76%. Third, administration of naloxone enhanced the responses of seven other afferent nerves to bradykinin by 85%. In contrast, in the absence of naloxone, cardiac afferent nerves consistently responded to repeated application of ATP (n = 7) or bradykinin (n = 7). These data suggest that peripheral opioid peptides suppress the responses of cardiac sympathetic afferent nerves to myocardial ischemia and ischemic mediators like ATP and bradykinin. PMID:23645463

MicroRNA-133 modulates the β1-adrenergic receptor transduction cascade.

PubMed

Castaldi, Alessandra; Zaglia, Tania; Di Mauro, Vittoria; Carullo, Pierluigi; Viggiani, Giacomo; Borile, Giulia; Di Stefano, Barbara; Schiattarella, Gabriele Giacomo; Gualazzi, Maria Giovanna; Elia, Leonardo; Stirparo, Giuliano Giuseppe; Colorito, Maria Luisa; Pironti, Gianluigi; Kunderfranco, Paolo; Esposito, Giovanni; Bang, Marie-Louise; Mongillo, Marco; Condorelli, Gianluigi; Catalucci, Daniele

2014-07-07

The sympathetic nervous system plays a fundamental role in the regulation of myocardial function. During chronic pressure overload, overactivation of the sympathetic nervous system induces the release of catecholamines, which activate β-adrenergic receptors in cardiomyocytes and lead to increased heart rate and cardiac contractility. However, chronic stimulation of β-adrenergic receptors leads to impaired cardiac function, and β-blockers are widely used as therapeutic agents for the treatment of cardiac disease. MicroRNA-133 (miR-133) is highly expressed in the myocardium and is involved in controlling cardiac function through regulation of messenger RNA translation/stability. To determine whether miR-133 affects β-adrenergic receptor signaling during progression to heart failure. Based on bioinformatic analysis, β1-adrenergic receptor (β1AR) and other components of the β1AR signal transduction cascade, including adenylate cyclase VI and the catalytic subunit of the cAMP-dependent protein kinase A, were predicted as direct targets of miR-133 and subsequently validated by experimental studies. Consistently, cAMP accumulation and activation of downstream targets were repressed by miR-133 overexpression in both neonatal and adult cardiomyocytes following selective β1AR stimulation. Furthermore, gain-of-function and loss-of-function studies of miR-133 revealed its role in counteracting the deleterious apoptotic effects caused by chronic β1AR stimulation. This was confirmed in vivo using a novel cardiac-specific TetON-miR-133 inducible transgenic mouse model. When subjected to transaortic constriction, TetON-miR-133 inducible transgenic mice maintained cardiac performance and showed attenuated apoptosis and reduced fibrosis compared with control mice. miR-133 controls multiple components of the β1AR transduction cascade and is cardioprotective during heart failure. © 2014 American Heart Association, Inc.

Sympathetic Nervous System Modulation of Inflammation and Remodeling in the Hypertensive Heart

PubMed Central

Levick, Scott P.; Murray, David B.; Janicki, Joseph S.; Brower, Gregory L.

2010-01-01

Chronic activation of the sympathetic nervous system (SNS) is a key component of cardiac hypertrophy and fibrosis. However, previous studies have provided evidence to also implicate inflammatory cells, including mast cells, in the development of cardiac fibrosis. The current study investigated the potential interaction of cardiac mast cells with the SNS. Eight week old male SHR were sympathectomized to establish the effect of the SNS on cardiac mast cell density, myocardial remodeling and cytokine production in the hypertensive heart. Age-matched WKY served as controls. Cardiac fibrosis and hypertension were significantly attenuated and left ventricular mass normalized while cardiac mast cell density was markedly increased in sympathectomized SHR. Sympathectomy normalized myocardial levels of IFN-γ, IL-6 and IL-10, but had no effect on IL-4. The effect of norepinephrine and substance P on isolated cardiac mast cell activation was investigated as potential mechanisms of interaction between the two. Only substance P elicited mast cell degranulation. Substance P was also shown to induce the production of angiotensin II by a mixed population of isolated cardiac inflammatory cells, including mast cells, lymphocytes and macrophages. These results demonstrate the ability of neuropeptides to regulate inflammatory cell function, providing a potential mechanism by which the SNS and afferent nerves may interact with inflammatory cells in the hypertensive heart. PMID:20048196

The sympathetic/parasympathetic imbalance in heart failure with reduced ejection fraction

PubMed Central

Floras, John S.; Ponikowski, Piotr

2015-01-01

Cardiovascular autonomic imbalance, a cardinal phenotype of human heart failure, has adverse implications for symptoms during wakefulness and sleep; for cardiac, renal, and immune function; for exercise capacity; and for lifespan and mode of death. The objectives of this Clinical Review are to summarize current knowledge concerning mechanisms for disturbed parasympathetic and sympathetic circulatory control in heart failure with reduced ejection fraction and its clinical and prognostic implications; to demonstrate the patient-specific nature of abnormalities underlying this common phenotype; and to illustrate how such variation provides opportunities to improve or restore normal sympathetic/parasympathetic balance through personalized drug or device therapy. PMID:25975657

Neural control of renal function in health and disease.

PubMed

DiBona, G F

1994-04-01

The renal sympathetic innervation of the kidney exerts significant effects on multiple aspects of renal function, including renal haemodynamics, tubular sodium and water reabsorption and renin secretion. These effects constitute an important control system which is important in the physiological regulation of arterial pressure and total body fluid and sodium homeostasis. Abnormalities in this regulatory mechanism have pathophysiological consequences and are manifest in clinically relevant human disease states. Decreased renal sympathetic nerve activity results in impaired renin secretion, the inability to conserve sodium normally and an attenuated ability to dispose of both acute and chronic sodium loads. Increased renal sympathetic nerve activity contributes significantly to the excess renal sodium retention and related renal abnormalities observed in both hypertension and oedema forming conditions, such as cardiac failure, cirrhosis and nephrotic syndrome.

Sympathetic neurons are a powerful driver of myocyte function in cardiovascular disease.

PubMed

Larsen, Hege E; Lefkimmiatis, Konstantinos; Paterson, David J

2016-12-14

Many therapeutic interventions in disease states of heightened cardiac sympathetic activity are targeted to the myocytes. However, emerging clinical data highlights a dominant role in disease progression by the neurons themselves. Here we describe a novel experimental model of the peripheral neuro-cardiac axis to study the neuron's ability to drive a myocyte cAMP phenotype. We employed a co-culture of neonatal ventricular myocytes and sympathetic stellate neurons from normal (WKY) and pro-hypertensive (SHR) rats that are sympathetically hyper-responsive and measured nicotine evoked cAMP responses in the myocytes using a fourth generation FRET cAMP sensor. We demonstrated the dominant role of neurons in driving the myocyte ß-adrenergic phenotype, where SHR cultures elicited heightened myocyte cAMP responses during neural activation. Moreover, cross-culturing healthy neurons onto diseased myocytes rescued the diseased cAMP response of the myocyte. Conversely, healthy myocytes developed a diseased cAMP response if diseased neurons were introduced. Our results provide evidence for a dominant role played by the neuron in driving the adrenergic phenotype seen in cardiovascular disease. We also highlight the potential of using healthy neurons to turn down the gain of neurotransmission, akin to a smart pre-synaptic ß-blocker.

[Tilt test and orthostatic intolerance: abnormalities in the neural sympathetic response to gravitational stimulus].

PubMed

Furlan, R

2001-05-01

In the present manuscript the different methodologies aimed at assessing the autonomic profile in humans during a gravitational stimulus have been described. In addition, strengths and drawbacks of the tilt test in relation to occasional orthostatic intolerance were addressed. Finally, different autonomic abnormalities underlying occasional and chronic orthostatic intolerance syndromes have been schematically highlighted. The direct recording of the neural sympathetic discharge from the peroneal nerve (MSNA), in spite of its invasive nature, still represents the recognized reference to quantify the changes in the sympathetic activity to the vessels attending postural modifications. The increase of plasma norepinephrine during a tilt test is achieved by both an increase in plasma spillover and a concomitant decrease in systemic clearance. Changes in the indices of cardiac sympathetic and vagal modulation may also be quantified during a tilt test by power spectrum analysis of RR interval variability. The spectral markers of cardiac autonomic control, if evaluated concomitantly with MSNA, may contribute to assess abnormalities in the regional distribution of the sympathetic activity to the heart and the vessels. The capability of the tilt test of reproducing a vasovagal event or of inducing "false positive responses" seems to be markedly affected by the age, thus suggesting that additional or different etiopathogenetic mechanisms might be involved in the loss of consciousness in older as compared to younger subjects. In subjects suffering from occasional or habitual neurally mediated syncope an increase or, respectively, a decrease in cardiac and vascular sympathetic modulation has been documented before the loss of consciousness. In patients with pure autonomic failure, a global dysautonomia affecting both the sympathetic and the vagal modulation to the heart, seems to be present. In chronic orthostatic intolerance, the most common form of dysautonomia of young women, an abnormal regional distribution of sympathetic activity has been hypothesized during up-right posture. Indeed, during standing a blunted increase of sympathetic activity to the vessels is attended by a cardiac sympathetic overactivity leading to an exaggerated tachycardia.

Metaiodobenzylguanidine (/sup 131/I) scintigraphy detects impaired myocardial sympathetic neuronal transport function of canine mechanical-overload heart failure

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rabinovitch, M.A.; Rose, C.P.; Rouleau, J.L.

1987-12-01

In heart failure secondary to chronic mechanical overload, cardiac sympathetic neurons demonstrate depressed catecholamine synthetic and transport function. To assess the potential of sympathetic neuronal imaging for detection of depressed transport function, serial scintigrams were acquired after the intravenous administration of metaiodobenzylguanidine (/sup 131/I) to 13 normal dogs, 3 autotransplanted (denervated) dogs, 5 dogs with left ventricular failure, and 5 dogs with compensated left ventricular hypertrophy due to a surgical arteriovenous shunt. Nine dogs were killed at 14 hours postinjection for determination of metaiodobenzylguanidine (/sup 131/I) and endogenous norepinephrine content in left atrium, left ventricle, liver, and spleen. By 4more » hours postinjection, autotransplanted dogs had a 39% reduction in mean left ventricular tracer accumulation, reflecting an absent intraneuronal tracer pool. Failure dogs demonstrated an accelerated early mean left ventricular tracer efflux rate (26.0%/hour versus 13.7%/hour in normals), reflecting a disproportionately increased extraneuronal tracer pool. They also showed reduced late left ventricular and left atrial concentrations of tracer, consistent with a reduced intraneuronal tracer pool. By contrast, compensated hypertrophy dogs demonstrated a normal early mean left ventricular tracer efflux rate (16.4%/hour) and essentially normal late left ventricular and left atrial concentrations of tracer. Metaiodobenzylguanidine (/sup 131/I) scintigraphic findings reflect the integrity of the cardiac sympathetic neuronal transport system in canine mechanical-overload heart failure. Metaiodobenzylguanidine (/sup 123/I) scintigraphy should be explored as a means of early detection of mechanical-overload heart failure in patients.« less

Heterogeneous response of cardiac sympathetic function to cardiac resynchronization therapy in heart failure documented by 11[C]-hydroxy-ephedrine and PET/CT.

PubMed

Capitanio, Selene; Nanni, Cristina; Marini, Cecilia; Bonfiglioli, Rachele; Martignani, Cristian; Dib, Bassam; Fuccio, Chiara; Boriani, Giuseppe; Picori, Lorena; Boschi, Stefano; Morbelli, Silvia; Fanti, Stefano; Sambuceti, Gianmario

2015-11-01

Cardiac resynchronization therapy (CRT) is an accepted treatment in patients with end-stage heart failure. PET permits the absolute quantification of global and regional homogeneity in cardiac sympathetic innervation. We evaluated the variation of cardiac adrenergic activity in patients with idiopathic heart failure (IHF) disease (NYHA III-IV) after CRT using (11)C-hydroxyephedrine (HED) PET/CT. Ten IHF patients (mean age = 68; range = 55-81; average left ventricular ejection fraction 26 ± 4%) implanted with a resynchronization device underwent three HED PET/CT studies: PET 1 one week after inactive device implantation; PET 2, one week after PET 1 under stimulated rhythm; PET 3, at 3 months under active CRT. A dedicated software (PMOD 3.4 version) was used to estimate global and regional cardiac uptake of HED through 17 segment polar maps. At baseline, HED uptake was heterogeneously distributed throughout the left ventricle with a variation coefficient of 18 ± 5%. This variable markedly decreased after three months CRT (12 ± 5%, p < 0.01). Interestingly, subdividing the 170 myocardial segments (17 segments of each patient multiplied by the number of patients) into two groups, according to the median value of tracer uptake expressed as % of maximal myocardial uptake (76%), we observed a different behaviour depending on baseline innervation: HED uptake significantly increased only in segments with "impaired innervation" (SUV 2.61 ± 0.92 at PET1 and 3.05 ± 1.67 at three months, p < 0.01). As shown by HED PET/CT uptake and distribution, improvement in homogeneity of myocardial neuronal function reflected a selective improvement of tracer uptake in regions with more severe neuronal damage. These finding supported the presence of a myocardial regional variability in response of cardiac sympathetic system to CRT and a systemic response involving remote tissues with rich adrenergic innervation. This work might contribute to identify imaging parameters that could predict the response to CRT therapy. Copyright © 2015 Elsevier Inc. All rights reserved.

Effect of fluorocarbons on acetylcholinesterase activity and some counter measures

NASA Technical Reports Server (NTRS)

Young, W.; Parker, J. A.

1975-01-01

An isolated vagal sympathetic heart system has been successfully used for the study of the effect of fluorocarbons (FCs) on cardiac performance and in situ enzyme activity. Dichlorodifluoromethane sensitizes this preparation to sympathetic stimulation and to exogenous epinephrine challenge. Partial and complete A-V block and even cardiac arrest have been induced by epinephrine challenge in the FC sensitized heart. Potassium chloride alone restores the rhythmicity but not the normal contractility of the heart in such a situation. Addition of glucose will, however, completely restore the normal function of the heart which is sensitized by dichlorodifluoromethane. The ED 50 values of acetylcholinesterase activity which are used as a measure of relative effectiveness of fluorocarbons are compared with the maximum permissible concentration. Kinetic studies indicate that all the fluorocarbons tested so far are noncompetitive.

Simultaneous measurements of cardiac noradrenaline spillover and sympathetic outflow to skeletal muscle in humans.

PubMed

Wallin, B G; Esler, M; Dorward, P; Eisenhofer, G; Ferrier, C; Westerman, R; Jennings, G

1992-01-01

1. Muscle sympathetic nerve activity (MSA) was recorded in the peroneal nerve at the knee by microneurography in ten healthy subjects and determinations were made simultaneously of intra-arterial blood pressure, and whole-body and cardiac noradrenaline spillover to plasma. Measurements were made at rest, during isometric handgrip at 30% of maximum power and during stress induced by forced mental arithmetic. 2. At rest there were significant positive correlations between spontaneous MSA (expressed as number of sympathetic bursts min-1) and both spillover of noradrenaline from the heart and concentration of noradrenaline in coronary sinus venous plasma. 3. Both isometric handgrip and mental arithmetic led to sustained increases of blood pressure, heart rate and MSA. Plasma concentrations of noradrenaline and spillover of noradrenaline (total body and cardiac) increased. In general the effects were more pronounced during handgrip than during stress. 4. When comparing effects during handgrip and stress the ratio between the fractional increases of MSA and cardiac noradrenaline spillover were significantly greater during handgrip. 5. The data suggest (a) that there are proportional interindividual differences in the strength of resting sympathetic activity to heart and skeletal muscle which are determined by a common mechanism and (b) that handgrip and mental stress are associated with differences in balance between sympathetic outflows to heart and skeletal muscle.

Loss of the transcription factor Meis1 prevents sympathetic neurons target-field innervation and increases susceptibility to sudden cardiac death

PubMed Central

Bouilloux, Fabrice; Thireau, Jérôme; Ventéo, Stéphanie; Farah, Charlotte; Karam, Sarah; Dauvilliers, Yves; Valmier, Jean; Copeland, Neal G; Jenkins, Nancy A; Richard, Sylvain; Marmigère, Frédéric

2016-01-01

Although cardio-vascular incidents and sudden cardiac death (SCD) are among the leading causes of premature death in the general population, the origins remain unidentified in many cases. Genome-wide association studies have identified Meis1 as a risk factor for SCD. We report that Meis1 inactivation in the mouse neural crest leads to an altered sympatho-vagal regulation of cardiac rhythmicity in adults characterized by a chronotropic incompetence and cardiac conduction defects, thus increasing the susceptibility to SCD. We demonstrated that Meis1 is a major regulator of sympathetic target-field innervation and that Meis1 deficient sympathetic neurons die by apoptosis from early embryonic stages to perinatal stages. In addition, we showed that Meis1 regulates the transcription of key molecules necessary for the endosomal machinery. Accordingly, the traffic of Rab5+ endosomes is severely altered in Meis1-inactivated sympathetic neurons. These results suggest that Meis1 interacts with various trophic factors signaling pathways during postmitotic neurons differentiation. DOI: http://dx.doi.org/10.7554/eLife.11627.001 PMID:26857994

Insulin resistance is associated with impaired cardiac sympathetic innervation in patients with heart failure.

PubMed

Paolillo, S; Rengo, G; Pellegrino, T; Formisano, R; Pagano, G; Gargiulo, P; Savarese, G; Carotenuto, R; Petraglia, L; Rapacciuolo, A; Perrino, C; Piscitelli, S; Attena, E; Del Guercio, L; Leosco, D; Trimarco, B; Cuocolo, A; Perrone-Filardi, P

2015-10-01

Insulin resistance (IR) represents, at the same time, cause and consequence of heart failure (HF) and affects prognosis in HF patients, but pathophysiological mechanisms remain unclear. Hyperinsulinemia, which characterizes IR, enhances sympathetic drive, and it can be hypothesized that IR is associated with impaired cardiac sympathetic innervation in HF. Yet, this hypothesis has never been investigated. Aim of the present observational study was to assess the relationship between IR and cardiac sympathetic innervation in non-diabetic HF patients. One hundred and fifteen patients (87% males; 65 ± 11.3 years) with severe-to-moderate HF (ejection fraction 32.5 ± 9.1%) underwent iodine-123 meta-iodobenzylguanidine ((123)I-MIBG) myocardial scintigraphy to assess sympathetic innervation and Homeostasis Model Assessment Insulin Resistance (HOMA-IR) evaluation to determine the presence of IR. From (123)I-MIBG imaging, early and late heart to mediastinum (H/M) ratios and washout rate were calculated. Seventy-two (63%) patients showed IR and 43 (37%) were non-IR. Early [1.68 (IQR 1.53-1.85) vs. 1.79 (IQR 1.66-1.95); P = 0.05] and late H/M ratio [1.50 (IQR 1.35-1.69) vs. 1.65 (IQR 1.40-1.85); P = 0.020] were significantly reduced in IR compared with non-IR patients. Early and late H/M ratio showed significant inverse correlation with fasting insulinemia and HOMA-IR. Cardiac sympathetic innervation is more impaired in patients with IR and HF compared with matched non-IR patients. These findings shed light on the relationship among IR, HF, and cardiac sympathetic nervous system. Additional studies are needed to clarify the pathogenetic relationship between IR and HF. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

Functional significance of cardiac reinnervation in heart transplant recipients.

PubMed

Schwaiblmair, M; von Scheidt, W; Uberfuhr, P; Ziegler, S; Schwaiger, M; Reichart, B; Vogelmeier, C

1999-09-01

There is accumulating evidence of structural sympathetic reinnervation after human cardiac transplantation. However, the functional significance of reinnervation in terms of exercise capacity has not been established as yet; we therefore investigated the influence of reinnervation on cardiopulmonary exercise testing. After orthotopic heart transplantation 35 patients (mean age, 49.1 +/- 8.4 years) underwent positron emission tomography with scintigraphically measured uptake of C11-hydroxyephedrine (HED), lung function testing, and cardiopulmonary exercise testing. Two groups were defined based on scintigraphic findings, indicating a denervated group (n = 15) with a HED uptake of 5.45%/min and a reinnervated group (n = 20) with a HED uptake of 10.59%/min. The two study groups did not show significant differences with regard to anthropometric data, number of rejection episodes, preoperative hemodynamics, and postoperative lung function data. The reinnervated group had a significant longer time interval from transplantation (1625 +/- 1069 versus 800 +/- 1316 days, p < .05). In transplant recipients with reinnervation, heart rate at maximum exercise (137 +/- 15 versus 120 +/- 20 beats/min, p = .012), peak oxygen uptake (21.0 +/- 4 versus 16.1 +/- 5 mL/min/kg, p = .006), peak oxygen pulse (12.4 +/- 2.9 versus 10.2 +/- 2.7 mL/min/beat, p = .031), and anaerobic threshold (11.2 +/- 1.8 versus 9.5 +/- 2.1 mL/min, p = .046) were significantly increased in comparison to denervated transplant recipients. Additionally, a decreased functional dead space ventilation (0.24 +/- 0.05 versus 0.30 +/- 0.05, p = .004) was observed in the reinnervated group. Our study results support the hypothesis that partial sympathetic reinnervation after cardiac transplantation is of functional significance. Sympathetic reinnervation enables an increased peak oxygen uptake. This is most probably due to partial restoration of the chronotropic and inotropic competence of the heart as well as an improved oxygen delivery to the exercising muscles and a reduced ventilation-perfusion mismatching.

Cardiovascular dysautonomia in Parkinson Disease: From pathophysiology to pathogenesis

PubMed Central

Goldstein, David S.

2011-01-01

Signs or symptoms of impaired autonomic regulation of the circulation often attend Parkinson disease (PD). This review covers biomarkers and mechanisms of autonomic cardiovascular abnormalities in PD and related alpha-synucleinopathies. The clearest clinical laboratory correlate of dysautonomia in PD is loss of myocardial noradrenergic innervation, detected by cardiac sympathetic neuroimaging. About 30–40% of PD patients have orthostatic hypotension (OH), defined as a persistent, consistent fall in systolic blood pressure of at least 20 mm Hg or diastolic blood pressure of at least 10 mm Hg within three minutes of change in position from supine to standing. Neuroimaging evidence of cardiac sympathetic denervation is universal in PD with OH (PD+OH). In PD without OH about half the patients have diffuse left ventricular myocardial sympathetic denervation, a substantial minority have partial denervation confined to the inferolateral or apical walls, and a small number have normal innervation. Among patients with partial denervation the neuronal loss invariably progresses over time, and in those with normal innervation at least some loss eventually becomes evident. Thus, cardiac sympathetic denervation in PD occurs independently of the movement disorder. PD+OH also entails extra-cardiac noradrenergic denervation, but this is not as severe as in pure autonomic failure. PD+OH patients have failure of both the parasympathetic and sympathetic components of the arterial baroreflex. OH in PD therefore seems to reflect a “triple whammy” of cardiac and extra-cardiac noradrenergic denervation and baroreflex failure. In contrast, most patients with multiple system atrophy, which can resemble PD+OH clinically, do not have evidence for cardiac or extra-cardiac noradrenergic denervation. Catecholamines in the neuronal cytoplasm are potentially toxic, via spontaneous and enzyme-catalyzed oxidation. Normally cytoplasmic catecholamines are efficiently taken up into vesicles via the vesicular monoamine transporter. The recent finding of decreased vesicular uptake in Lewy body diseases therefore suggests a pathogenetic mechanism for loss of catecholaminergic neurons in the periphery and brain. PMID:22094370

Bioelectronic block of paravertebral sympathetic nerves mitigates post-myocardial infarction ventricular arrhythmias.

PubMed

Chui, Ray W; Buckley, Una; Rajendran, Pradeep S; Vrabec, Tina; Shivkumar, Kalyanam; Ardell, Jeffrey L

2017-11-01

Autonomic dysfunction contributes to induction of ventricular tachyarrhythmia (VT). To determine the efficacy of charge-balanced direct current (CBDC), applied to the T1-T2 segment of the paravertebral sympathetic chain, on VT inducibility post-myocardial infarction (MI). In a porcine model, CBDC was applied in acute animals (n = 7) to optimize stimulation parameters for sympathetic blockade and in chronic MI animals (n = 7) to evaluate the potential for VTs. Chronic MI was induced by microsphere embolization of the left anterior descending coronary artery. At termination, in anesthetized animals and following thoracotomy, an epicardial sock array was placed over both ventricles and a quadripolar carousel electrode positioned underlying the right T1-T2 paravertebral chain. In acute animals, the efficacy of CBDC carousel (CBDCC) block was assessed by evaluating cardiac function during T2 paravertebral ganglion stimulation with and without CBDCC. In chronic MI animals, VT inducibility was assessed by extrasystolic (S1-S2) stimulations at baseline and under >66% CBDCC blockade of T2-evoked sympathoexcitation. CBDCC demonstrated a current-dependent and reversible block without impacting basal cardiac function. VT was induced at baseline in all chronic MI animals. One animal died after baseline induction. Of the 6 remaining animals, only 1 was reinducible with simultaneous CBDCC application (P < .002 from baseline). The ventricular effective refractory period (VERP) was prolonged with CBDCC (323 ± 26 ms) compared to baseline (271 ± 32 ms) (P < .05). Axonal block of the T1-T2 paravertebral chain with CBDCC reduced VT in a chronic MI model. CBDCC prolonged VERP, without altering baseline cardiac function, resulting in improved electrical stability. Copyright © 2017 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Iodine-123 metaiodobenzylguanidine imaging of the heart in idiopathic congestive cardiomyopathy and cardiac transplants

DOE Office of Scientific and Technical Information (OSTI.GOV)

Glowniak, J.V.; Turner, F.E.; Gray, L.L.

1989-07-01

Iodine-123 metaiodobenzylguanidine ((/sup 123/I)MIBG) is a norepinephrine analog which can be used to image the sympathetic innervation of the heart. In this study, cardiac imaging with (/sup 123/I)MIBG was performed in patients with idiopathic congestive cardiomyopathy and compared to normal controls. Initial uptake, half-time of tracer within the heart, and heart to lung ratios were all significantly reduced in patients compared to normals. Uptake in lungs, liver, salivary glands, and spleen was similar in controls and patients with cardiomyopathy indicating that decreased MIBG uptake was not a generalized abnormality in these patients. Iodine-123 MIBG imaging was also performed in cardiacmore » transplant patients to determine cardiac nonneuronal uptake. Uptake in transplants was less than 10% of normals in the first 2 hr and nearly undetectable after 16 hr. The decreased uptake of MIBG suggests cardiac sympathetic nerve dysfunction while the rapid washout of MIBG from the heart suggests increased cardiac sympathetic nerve activity in idiopathic congestive cardiomyopathy.« less

Pyridostigmine Restores Cardiac Autonomic Balance after Small Myocardial Infarction in Mice

PubMed Central

Durand, Marina T.; Becari, Christiane; de Oliveira, Mauro; do Carmo, Jussara M.; Aguiar Silva, Carlos Alberto; Prado, Cibele M.; Fazan, Rubens; Salgado, Helio C.

2014-01-01

The effect of pyridostigmine (PYR) - an acetylcholinesterase inhibitor - on hemodynamics and cardiac autonomic control, was never studied in conscious myocardial infarcted mice. Telemetry transmitters were implanted into the carotid artery under isoflurane anesthesia. Seven to ten days after recovery from the surgery, basal arterial pressure and heart rate were recorded, while parasympathetic and sympathetic tone (ΔHR) was evaluated by means of methyl atropine and propranolol. After the basal hemodynamic recording the mice were subjected to left coronary artery ligation for producing myocardial infarction (MI), or sham operation, and implantation of minipumps filled with PYR or saline. Separate groups of anesthetized (isoflurane) mice previously (4 weeks) subjected to MI, or sham coronary artery ligation, were submitted to cardiac function examination. The mice exhibited an infarct length of approximately 12%, no change in arterial pressure and increased heart rate only in the 1st week after MI. Vagal tone decreased in the 1st week, while the sympathetic tone was increased in the 1st and 4th week after MI. PYR prevented the increase in heart rate but did not affect the arterial pressure. Moreover, PYR prevented the increase in sympathetic tone throughout the 4 weeks. Concerning the parasympathetic tone, PYR not only impaired its attenuation in the 1st week, but enhanced it in the 4th week. MI decreased ejection fraction and increased diastolic and systolic volume. Therefore, the pharmacological increase of peripheral acetylcholine availability by means of PYR prevented tachycardia, increased parasympathetic and decreased sympathetic tone after MI in mice. PMID:25133392

Sympathetic cardiac hyperinnervation and atrial autonomic imbalance in diet-induced obesity promote cardiac arrhythmias

PubMed Central

Hasan, Wohaib; Streiff, Cole T.; Houle, Jennifer C.; Woodward, William R.; Giraud, George D.; Brooks, Virginia L.; Habecker, Beth A.

2013-01-01

Obesity increases the risk of arrhythmias and sudden cardiac death, but the mechanisms are unknown. This study tested the hypothesis that obesity-induced cardiac sympathetic outgrowth and hyperinnervation promotes the development of arrhythmic events. Male Sprague-Dawley rats (250–275 g), fed a high-fat diet (33% kcal/fat), diverged into obesity-resistant (OR) and obesity-prone (OP) groups and were compared with rats fed normal chow (13% kcal/fat; CON). In vitro experiments showed that both OR and OP rats exhibited hyperinnervation of the heart and high sympathetic outgrowth compared with CON rats, even though OR rats are not obese. Despite the hyperinnervation and outgrowth, we showed that, in vivo, OR rats were less susceptible to arrhythmic events after an intravenous epinephrine challenge compared with OP rats. On examining total and stimulus-evoked neurotransmitter levels in an ex vivo system, we demonstrate that atrial acetylcholine content and release were attenuated in OP compared with OR and CON groups. OP rats also expressed elevated atrial norepinephrine content, while norepinephrine release was suppressed. These findings suggest that the consumption of a high-fat diet, even in the absence of overt obesity, stimulates sympathetic outgrowth and hyperinnervation of the heart. However, normalized cardiac parasympathetic nervous system control may protect the heart from arrhythmic events. PMID:24014675

Sympathetic restraint of respiratory sinus arrhythmia: implications for vagal-cardiac tone assessment in humans

NASA Technical Reports Server (NTRS)

Taylor, J. A.; Myers, C. W.; Halliwill, J. R.; Seidel, H.; Eckberg, D. L.

2001-01-01

Clinicians and experimentalists routinely estimate vagal-cardiac nerve traffic from respiratory sinus arrhythmia. However, evidence suggests that sympathetic mechanisms may also modulate respiratory sinus arrhythmia. Our study examined modulation of respiratory sinus arrhythmia by sympathetic outflow. We measured R-R interval spectral power in 10 volunteers that breathed sequentially at 13 frequencies, from 15 to 3 breaths/min, before and after beta-adrenergic blockade. We fitted changes of respiratory frequency R-R interval spectral power with a damped oscillator model: frequency-dependent oscillations with a resonant frequency, generated by driving forces and modified by damping influences. beta-Adrenergic blockade enhanced respiratory sinus arrhythmia at all frequencies (at some, fourfold). The damped oscillator model fit experimental data well (39 of 40 ramps; r = 0.86 +/- 0.02). beta-Adrenergic blockade increased respiratory sinus arrhythmia by amplifying respiration-related driving forces (P < 0.05), without altering resonant frequency or damping influences. Both spectral power data and the damped oscillator model indicate that cardiac sympathetic outflow markedly reduces heart period oscillations at all frequencies. This challenges the notion that respiratory sinus arrhythmia is mediated simply by vagal-cardiac nerve activity. These results have important implications for clinical and experimental estimation of human vagal cardiac tone.

Myocardial ischaemia and the cardiac nervous system.

PubMed

Armour, J A

1999-01-01

The intrinsic cardiac nervous system has been classically considered to contain only parasympathetic efferent postganglionic neurones which receive inputs from medullary parasympathetic efferent preganglionic neurones. In such a view, intrinsic cardiac ganglia act as simple relay stations of parasympathetic efferent neuronal input to the heart, the major autonomic control of the heart purported to reside solely in the brainstem and spinal cord. Data collected over the past two decades indicate that processing occurs within the mammalian intrinsic cardiac nervous system which involves afferent neurones, local circuit neurones (interconnecting neurones) as well as both sympathetic and parasympathetic efferent postganglionic neurones. As such, intrinsic cardiac ganglionic interactions represent the organ component of the hierarchy of intrathoracic nested feedback control loops which provide rapid and appropriate reflex coordination of efferent autonomic neuronal outflow to the heart. In such a concept, the intrinsic cardiac nervous system acts as a distributive processor, integrating parasympathetic and sympathetic efferent centrifugal information to the heart in addition to centripetal information arising from cardiac sensory neurites. A number of neurochemicals have been shown to influence the interneuronal interactions which occur within the intrathoracic cardiac nervous system. For instance, pharmacological interventions that modify beta-adrenergic or angiotensin II receptors affect cardiomyocyte function not only directly, but indirectly by influencing the capacity of intrathoracic neurones to regulate cardiomyocytes. Thus, current pharmacological management of heart disease may influence cardiomyocyte function directly as well as indirectly secondary to modifying the cardiac nervous system. This review presents a brief summary of developing concepts about the role of the cardiac nervous system in regulating the normal heart. In addition, it provides some tentative ideas concerning the importance of this nervous system in cardiac disease states with a view to stimulating further interest in neural control of the heart so that appropriate neurocardiological strategies can be devised for the management of heart disease.

Autonomic and Renal Alterations in the Offspring of Sleep-Restricted Mothers During Late Pregnancy.

PubMed

Raimundo, Joyce R S; Bergamaschi, Cassia T; Campos, Ruy R; Palma, Beatriz D; Tufik, Sergio; Gomes, Guiomar N

2016-09-01

Considering that changes in the maternal environment may result in changes in progeny, the aim of this study was to investigate the influence of sleep restriction during the last week of pregnancy on renal function and autonomic responses in male descendants at an adult age. After confirmation of pregnancy, female Wistar rats were randomly assigned to either a control or a sleep restriction group. The sleep-restricted rats were subjected to sleep restriction using the multiple platforms method for over 20 hours per day between the 14th and 20th day of pregnancy. After delivery, the litters were limited to 6 offspring that were designated as offspring from control and offspring from sleep-restricted mothers. Indirect measurements of systolic blood pressure (BPi), renal plasma flow, glomerular filtration rate, glomerular area and number of glomeruli per field were evaluated at three months of age. Direct measurements of cardiovascular function (heart rate and mean arterial pressure), cardiac sympathetic tone, cardiac parasympathetic tone, and baroreflex sensitivity were evaluated at four months of age. The sleep-restricted offspring presented increases in BPi, glomerular filtration rate and glomerular area compared with the control offspring. The sleep-restricted offspring also showed higher basal heart rate, increased mean arterial pressure, increased sympathetic cardiac tone, decreased parasympathetic cardiac tone and reduced baroreflex sensitivity. Our data suggest that reductions in sleep during the last week of pregnancy lead to alterations in cardiovascular autonomic regulation and renal morpho-functional changes in offspring, triggering increases in blood pressure.

BDNF - A key player in cardiovascular system.

PubMed

Pius-Sadowska, Ewa; Machaliński, Bogusław

2017-09-01

Neurotrophins (NTs) were first identified as target-derived survival factors for neurons of the central and peripheral nervous system (PNS). They are known to control neural cell fate, development and function. Independently of their neuronal properties, NTs exert unique cardiovascular activity. The heart is innervated by sensory, sympathetic and parasympathetic neurons, which require NTs during early development and in the establishment of mature properties, contributing to the maintenance of cardiovascular homeostasis. The identification of molecular mechanisms regulated by NTs and involved in the crosstalk between cardiac sympathetic nerves, cardiomyocytes, cardiac fibroblasts, and vascular cells, has a fundamental importance in both normal heart function and disease. The article aims to review the recent data on the effects of Brain-Derived Neurotrophic Factor (BDNF) on various cardiovascular neuronal and non-neuronal functions such as the modulation of synaptic properties of autonomic neurons, axonal outgrowth and sprouting, formation of the vascular and neural networks, smooth muscle migration, and control of endothelial cell survival and cardiomyocytes. Understanding these mechanisms may be crucial for developing novel therapeutic strategies, including stem cell-based therapies. Copyright © 2017 Elsevier Ltd. All rights reserved.

Cardiac diastolic and autonomic dysfunction are aggravated by central chemoreflex activation in heart failure with preserved ejection fraction rats

PubMed Central

Toledo, Camilo; Andrade, David C.; Lucero, Claudia; Arce‐Alvarez, Alexis; Díaz, Hugo S.; Aliaga, Valentín; Schultz, Harold D.; Marcus, Noah J.; Manríquez, Mónica; Faúndez, Marcelo

2017-01-01

Key points Heart failure with preserved ejection fraction (HFpEF) is associated with disordered breathing patterns, and sympatho‐vagal imbalance.Although it is well accepted that altered peripheral chemoreflex control plays a role in the progression of heart failure with reduced ejection fraction (HFrEF), the pathophysiological mechanisms underlying deterioration of cardiac function in HFpEF are poorly understood.We found that central chemoreflex is enhanced in HFpEF and neuronal activation is increased in pre‐sympathetic regions of the brainstem.Our data showed that activation of the central chemoreflex pathway in HFpEF exacerbates diastolic dysfunction, worsens sympatho‐vagal imbalance and markedly increases the incidence of cardiac arrhythmias in rats with HFpEF. Abstract Heart failure (HF) patients with preserved ejection fraction (HFpEF) display irregular breathing, sympatho‐vagal imbalance, arrhythmias and diastolic dysfunction. It has been shown that tonic activation of the central and peripheral chemoreflex pathway plays a pivotal role in the pathophysiology of HF with reduced ejection fraction. In contrast, no studies to date have addressed chemoreflex function or its effect on cardiac function in HFpEF. Therefore, we tested whether peripheral and central chemoreflexes are hyperactive in HFpEF and if chemoreflex activation exacerbates cardiac dysfunction and autonomic imbalance. Sprague‐Dawley rats (n = 32) were subjected to sham or volume overload to induce HFpEF. Resting breathing variability, chemoreflex gain, cardiac function and sympatho‐vagal balance, and arrhythmia incidence were studied. HFpEF rats displayed [mean ± SD; chronic heart failure (CHF) vs. Sham, respectively] a marked increase in the incidence of apnoeas/hypopnoeas (20.2 ± 4.0 vs. 9.7 ± 2.6 events h−1), autonomic imbalance [0.6 ± 0.2 vs. 0.2 ± 0.1 low/high frequency heart rate variability (LF/HFHRV)] and cardiac arrhythmias (196.0 ± 239.9 vs. 19.8 ± 21.7 events h−1). Furthermore, HFpEF rats showed increase central chemoreflex sensitivity but not peripheral chemosensitivity. Accordingly, hypercapnic stimulation in HFpEF rats exacerbated increases in sympathetic outflow to the heart (229.6 ± 43.2% vs. 296.0 ± 43.9% LF/HFHRV, normoxia vs. hypercapnia, respectively), incidence of cardiac arrhythmias (196.0 ± 239.9 vs. 576.7 ± 472.9 events h−1) and diastolic dysfunction (0.008 ± 0.004 vs. 0.027 ± 0.027 mmHg μl−1). Importantly, the cardiovascular consequences of central chemoreflex activation were related to sympathoexcitation since these effects were abolished by propranolol. The present results show that the central chemoreflex is enhanced in HFpEF and that acute activation of central chemoreceptors leads to increases of cardiac sympathetic outflow, cardiac arrhythmogenesis and impairment in cardiac function in rats with HFpEF. PMID:28181258

The intrinsic circadian clock within the cardiomyocyte directly regulates myocardial gene expression, metabolism, and function

USDA-ARS?s Scientific Manuscript database

Circadian rhythms have been firmly established in both cardiovascular physiology (e.g., heart rate, cardiac output) and pathophysiology (e.g., arrhythmias). These phenomena have been attributed primarily to circadian rhythms in neurohumoral influences, such as sympathetic activity. Virtually every...

Vidarabine, an Anti-Herpes Virus Agent, Protects Against the Development of Heart Failure With Relatively Mild Side-Effects on Cardiac Function in a Canine Model of Pacing-Induced Dilated Cardiomyopathy.

PubMed

Nakamura, Takashi; Fujita, Takayuki; Kishimura, Megumi; Suita, Kenji; Hidaka, Yuko; Cai, Wenqian; Umemura, Masanari; Yokoyama, Utako; Uechi, Masami; Ishikawa, Yoshihiro

2016-11-25

In heart failure patients, chronic hyperactivation of sympathetic signaling is known to exacerbate cardiac dysfunction. In this study, the cardioprotective effect of vidarabine, an anti-herpes virus agent, which we identified as a cardiac adenylyl cyclase inhibitor, in dogs with pacing-induced dilated cardiomyopathy (DCM) was evaluated. In addition, the adverse effects of vidarabine on basal cardiac function was compared to those of the β-blocker, carvedilol.Methods and Results:Vidarabine and carvedilol attenuated the development of pacing-induced systolic dysfunction significantly and with equal effectiveness. Both agents also inhibited the development of cardiac apoptosis and fibrosis and reduced the Na + -Ca 2+ exchanger-1 protein level in the heart. Importantly, carvedilol significantly enlarged the left ventricle and atrium; vidarabine, in contrast, did not. Vidarabine-treated dogs maintained cardiac response to β-AR stimulation better than carvedilol-treated dogs did. Vidarabine may protect against pacing-induced DCM with less suppression of basal cardiac function than carvedilol in a dog model. (Circ J 2016; 80: 2496-2505).

Sympathetic- and Parasympathetic-linked Cardiac Function and Prediction of Externalizing Behavior, Emotion Regulation, and Prosocial Behavior among Preschoolers Treated for ADHD

PubMed Central

Beauchaine, Theodore P.; Gatzke-Kopp, Lisa; Neuhaus, Emily; Chipman, Jane; Reid, M. Jamila; Webster-Stratton, Carolyn

2014-01-01

Objective To evaluate measures of cardiac activity and reactivity as prospective biomarkers of treatment response to an empirically-supported behavioral intervention for attention-deficit/hyperactivity disorder (ADHD). Method Cardiac pre-ejection period (PEP), an index of sympathetic-linked cardiac activity, and respiratory sinus arrhythmia (RSA), and index of parasympathetic-linked cardiac activity, were assessed among 99 preschool children (ages 4–6 years) with ADHD both at rest and in response to behavioral challenge, before participants and their parents completed one of two versions of the Incredible Years parent and child interventions. Results Main effects of PEP activity and reactivity, and of RSA activity and reactivity were found. Although sample-wide improvements in behavior were observed at post treatment, those who exhibited lengthened cardiac PEP at rest and reduced PEP reactivity to incentives scored higher on measures of conduct problems and aggression both before and after treatment. In contrast, children who exhibited lower baseline RSA and greater RSA withdrawal scored lower on prosocial behavior before and after treatment. Finally, children who exhibited greater RSA withdrawal scored lower on emotion regulation before and after treatment. Conclusions We discuss these findings in terms of (a) individual differences in underlying neurobiological systems subserving appetitive (i.e., approach) motivation, emotion regulation, and social affiliation, and (b) the need to develop more intensive interventions targeting neurobiologically vulnerable children. PMID:23544677

Sympathetic- and parasympathetic-linked cardiac function and prediction of externalizing behavior, emotion regulation, and prosocial behavior among preschoolers treated for ADHD.

PubMed

Beauchaine, Theodore P; Gatzke-Kopp, Lisa; Neuhaus, Emily; Chipman, Jane; Reid, M Jamila; Webster-Stratton, Carolyn

2013-06-01

To evaluate measures of cardiac activity and reactivity as prospective biomarkers of treatment response to an empirically supported behavioral intervention for attention-deficit/hyperactivity disorder (ADHD). Cardiac preejection period (PEP), an index of sympathetic-linked cardiac activity, and respiratory sinus arrhythmia (RSA), an index of parasympathetic-linked cardiac activity, were assessed among 99 preschool children (ages 4-6 years) with ADHD both at rest and in response to behavioral challenge, before participants and their parents completed 1 of 2 versions of the Incredible Years parent and child interventions. Main effects of PEP activity and reactivity and of RSA activity and reactivity were found. Although samplewide improvements in behavior were observed at posttreatment, those who exhibited lengthened cardiac PEP at rest and reduced PEP reactivity to incentives scored higher on measures of conduct problems and aggression both before and after treatment. In contrast, children who exhibited lower baseline RSA and greater RSA withdrawal scored lower on prosocial behavior before and after treatment. Finally, children who exhibited greater RSA withdrawal scored lower on emotion regulation before and after treatment. We discuss these findings in terms of (a) individual differences in underlying neurobiological systems subserving appetitive (i.e., approach) motivation, emotion regulation, and social affiliation and (b) the need to develop more intensive interventions targeting neurobiologically vulnerable children.

Undiscovered role of endogenous thromboxane A2 in activation of cardiac sympathetic afferents during ischaemia

PubMed Central

Fu, Liang-Wu; Guo, Zhi-Ling; Longhurst, John C

2008-01-01

Myocardial ischaemia activates blood platelets, which in turn stimulate cardiac sympathetic afferents, leading to chest pain and sympathoexcitatory reflex cardiovascular responses. Previous studies have shown that activated platelets stimulate ischaemically sensitive cardiac sympathetic afferents, and that thromboxane A2 (TxA2) is one of the mediators released from activated platelets during myocardial ischaemia. The present study tested the hypothesis that endogenous TxA2 stimulates cardiac afferents during ischaemia through direct activation of TxA2 (TP) receptors coupled with the phospholipase C–protein kinase C (PLC–PKC) cellular pathway. Nerve activity of single unit cardiac sympathetic afferents was recorded from the left sympathetic chain or rami communicantes (T2–T5) in anaesthetized cats. Single fields of 39 afferents (conduction velocity = 0.27–3.65 m s−1) were identified in the left or right ventricle initially with mechanical stimulation and confirmed with a stimulating electrode. Five minutes of myocardial ischaemia stimulated all 39 cardiac afferents (8 Aδ-, 31 C-fibres) and the responses of these 39 afferents to chemical stimuli were further studied in the following four protocols. In the first protocol, 2.5, 5 and 10 μg of the TxA2 mimetic, U46619, injected into the left atrium (LA), stimulated seven ischaemically sensitive cardiac afferents in a dose-dependent manner. Second, BM13,177, a selective TxA2 receptor antagonist, abolished the responses of six afferents to 5 μg of U46619 injected into the left atrium and attenuated the ischaemia-related increase in activity of seven other afferents by 44%. In contrast, cardiac afferents, in the absence of TP receptor blockade responded consistently to repeated administration of U46619 (n = 6) and to recurrent myocardial ischaemia (n = 7). In the fourth protocol, administration of PKC-(19–36), a selective PKC inhibitor, attenuated the responses of six other cardiac afferents to U46619 by 38%. Finally, using an immunohistochemical staining approach, we observed that TP receptors were expressed in cardiac sensory neurons in thoracic dorsal root ganglia. Taken together, these data indicate that endogenous TxA2 contributes to the activation of cardiac afferents during myocardial ischaemia through direct stimulation of TP receptors probably located in the cardiac sensory nervous system and that the stimulating effect of TxA2 on cardiac afferents is dependent, at least in part, upon the PLC–PKC cellular pathway. PMID:18483073

Predominance of Intrinsic Mechanism of Resting Heart Rate Control and Preserved Baroreflex Sensitivity in Professional Cyclists after Competitive Training.

PubMed

Azevedo, Luciene Ferreira; Perlingeiro, Patricia; Hachul, Denise Tessariol; Gomes-Santos, Igor Lucas; Tsutsui, Jeane Mike; Negrao, Carlos Eduardo; De Matos, Luciana D N J

2016-01-01

Different season trainings may influence autonomic and non-autonomic cardiac control of heart rate and provokes specific adaptations on heart's structure in athletes. We investigated the influence of transition training (TT) and competitive training (CT) on resting heart rate, its mechanisms of control, spontaneous baroreflex sensitivity (BRS) and relationships between heart rate mechanisms and cardiac structure in professional cyclists (N = 10). Heart rate (ECG) and arterial blood pressure (Pulse Tonometry) were recorded continuously. Autonomic blockade was performed (atropine-0.04 mg.kg-1; esmolol-500 μg.kg-1 = 0.5 mg). Vagal effect, intrinsic heart rate, parasympathetic (n) and sympathetic (m) modulations, autonomic influence, autonomic balance and BRS were calculated. Plasma norepinephrine (high-pressure liquid chromatography) and cardiac structure (echocardiography) were evaluated. Resting heart rate was similar in TT and CT. However, vagal effect, intrinsic heart rate, autonomic influence and parasympathetic modulation (higher n value) decreased in CT (P≤0.05). Sympathetic modulation was similar in both trainings. The autonomic balance increased in CT but still showed parasympathetic predominance. Cardiac diameter, septum and posterior wall thickness and left ventricular mass also increased in CT (P<0.05) as well as diastolic function. We observed an inverse correlation between left ventricular diastolic diameter, septum and posterior wall thickness and left ventricular mass with intrinsic heart rate. Blood pressure and BRS were similar in both trainings. Intrinsic heart rate mechanism is predominant over vagal effect during CT, despite similar resting heart rate. Preserved blood pressure levels and BRS during CT are probably due to similar sympathetic modulation in both trainings.

Chaotic behavior of renal sympathetic nerve activity: effect of baroreceptor denervation and cardiac failure.

PubMed

DiBona, G F; Jones, S Y; Sawin, L L

2000-09-01

Nonlinear dynamic analysis was used to examine the chaotic behavior of renal sympathetic nerve activity in conscious rats subjected to either complete baroreceptor denervation (sinoaortic and cardiac baroreceptor denervation) or induction of congestive heart failure (CHF). The peak interval sequence of synchronized renal sympathetic nerve discharge was extracted and used for analysis. In control rats, this yielded a system whose correlation dimension converged to a low value over the embedding dimension range of 10-15 and whose greatest Lyapunov exponent was positive. Complete baroreceptor denervation was associated with a decrease in the correlation dimension of the system (before 2.65 +/- 0.27, after 1.64 +/- 0.17; P < 0.01) and a reduction in chaotic behavior (greatest Lyapunov exponent: 0.201 +/- 0.008 bits/data point before, 0.177 +/- 0.004 bits/data point after, P < 0.02). CHF, a state characterized by impaired sinoaortic and cardiac baroreceptor regulation of renal sympathetic nerve activity, was associated with a similar decrease in the correlation dimension (control 3.41 +/- 0.23, CHF 2.62 +/- 0.26; P < 0.01) and a reduction in chaotic behavior (greatest Lyapunov exponent: 0.205 +/- 0.048 bits/data point control, 0.136 +/- 0.033 bits/data point CHF, P < 0.02). These results indicate that removal of sinoaortic and cardiac baroreceptor regulation of renal sympathetic nerve activity, occurring either physiologically or pathophysiologically, is associated with a decrease in the correlation dimensions of the system and a reduction in chaotic behavior.

Inhibition of N-type Ca2+ channels ameliorates an imbalance in cardiac autonomic nerve activity and prevents lethal arrhythmias in mice with heart failure.

PubMed

Yamada, Yuko; Kinoshita, Hideyuki; Kuwahara, Koichiro; Nakagawa, Yasuaki; Kuwabara, Yoshihiro; Minami, Takeya; Yamada, Chinatsu; Shibata, Junko; Nakao, Kazuhiro; Cho, Kosai; Arai, Yuji; Yasuno, Shinji; Nishikimi, Toshio; Ueshima, Kenji; Kamakura, Shiro; Nishida, Motohiro; Kiyonaka, Shigeki; Mori, Yasuo; Kimura, Takeshi; Kangawa, Kenji; Nakao, Kazuwa

2014-10-01

Dysregulation of autonomic nervous system activity can trigger ventricular arrhythmias and sudden death in patients with heart failure. N-type Ca(2+) channels (NCCs) play an important role in sympathetic nervous system activation by regulating the calcium entry that triggers release of neurotransmitters from peripheral sympathetic nerve terminals. We have investigated the ability of NCC blockade to prevent lethal arrhythmias associated with heart failure. We compared the effects of cilnidipine, a dual N- and L-type Ca(2+) channel blocker, with those of nitrendipine, a selective L-type Ca(2+) channel blocker, in transgenic mice expressing a cardiac-specific, dominant-negative form of neuron-restrictive silencer factor (dnNRSF-Tg). In this mouse model of dilated cardiomyopathy leading to sudden arrhythmic death, cardiac structure and function did not significantly differ among the control, cilnidipine, and nitrendipine groups. However, cilnidipine dramatically reduced arrhythmias in dnNRSF-Tg mice, significantly improving their survival rate and correcting the imbalance between cardiac sympathetic and parasympathetic nervous system activity. A β-blocker, bisoprolol, showed similar effects in these mice. Genetic titration of NCCs, achieved by crossing dnNRSF-Tg mice with mice lacking CACNA1B, which encodes the α1 subunit of NCCs, improved the survival rate. With restoration of cardiac autonomic balance, dnNRSF-Tg;CACNA1B(+/-) mice showed fewer malignant arrhythmias than dnNRSF-Tg;CACNA1B(+/+) mice. Both pharmacological blockade of NCCs and their genetic titration improved cardiac autonomic balance and prevented lethal arrhythmias in a mouse model of dilated cardiomyopathy and sudden arrhythmic death. Our findings suggest that NCC blockade is a potentially useful approach to preventing sudden death in patients with heart failure. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.

Effects of nitric oxide synthase inhibition on sympathetically-mediated tachycardia

NASA Technical Reports Server (NTRS)

Whalen, E. J.; Johnson, A. K.; Lewis, S. J.

1999-01-01

The aim of the present study was to determine whether inhibition of nitric oxide (NO) synthesis directly alters the tachycardia produced by sympathetically-derived norepinephrine. The NO synthase inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME; 50 micromol/kg, i.v.), produced a marked rise in mean arterial blood pressure. This pressor response was associated with a fall in heart rate which involved the withdrawal of cardiac sympathetic nerve activity. The NO-donor, sodium nitroprusside (5 microg/kg, i.v.), produced a pronounced fall in mean arterial blood pressure but only a minor increase in heart rate. The beta-adrenoceptor agonist, isoproterenol (0.5 micromol/kg, i.v.), and the membrane-permeable cAMP analogue, 8-(4-chlorophenylthiol)-cAMP (10 micromol/kg, i.v.), produced falls in mean arterial blood pressure and pronounced increases in heart rate. The indirectly acting sympathomimetic agent, tyramine (0.5 mg/kg, i.v.), produced a pressor response and a tachycardia. The effects of sodium nitroprusside, tyramine, isoproterenol and 8-(4-chlorophenylthiol)-cAMP on mean arterial blood pressure were not markedly affected by L-NAME. However, the tachycardia produced by these agents was considerably exaggerated in the presence of this NO synthesis inhibitor. These findings suggest that L-NAME potentiates the tachycardia produced by sympathetically-derived norepinephrine. The increased responsiveness to norepinephrine may involve (i) a rapid up-regulation of cardiac beta1-adrenoceptors and cAMP signaling in cardiac pacemaker cells due to the loss of the inhibitory influence of cardiac NO, and (ii) the up-regulation of beta1-adrenoceptor-mediated signal transduction processes in response to the L-NAME-induced withdrawal of cardiac sympathetic nerve activity.

Resting sympathetic arousal moderates the association between parasympathetic reactivity and working memory performance in adults reporting high levels of life stress.

PubMed

Giuliano, Ryan J; Gatzke-Kopp, Lisa M; Roos, Leslie E; Skowron, Elizabeth A

2017-08-01

The neurovisceral integration model stipulates that autonomic function plays a critical role in the regulation of higher-order cognitive processes, yet most work to date has examined parasympathetic function in isolation from sympathetic function. Furthermore, the majority of work has been conducted on normative samples, which typically demonstrate parasympathetic withdrawal to increase arousal needed to complete cognitive tasks. Little is known about how autonomic regulation supports cognitive function in populations exposed to high levels of stress, which is critical given that chronic stress exposure alters autonomic function. To address this, we sought to characterize how parasympathetic (high-frequency heart rate variability, HF-HRV) and sympathetic (preejection period, PEP) measures of cardiac function contribute to individual differences in working memory (WM) capacity in a sample of high-risk women. HF-HRV and PEP were measured at rest and during a visual change detection measure of WM. Multilevel modeling was used to examine within-person fluctuations in WM performance throughout the task concurrently with HF-HRV and PEP, as well as between-person differences as a function of resting HF-HRV and PEP levels. Results indicate that resting PEP moderated the association between HF-HRV reactivity and WM capacity. Increases in WM capacity across the task were associated with increases in parasympathetic activity, but only among individuals with longer resting PEP (lower sympathetic arousal). Follow-up analyses showed that shorter resting PEP was associated with greater cumulative risk exposure. These results support the autonomic space framework, in that the relationship between behavior and parasympathetic function appears dependent on resting sympathetic activation. © 2017 Society for Psychophysiological Research.

Resting sympathetic arousal moderates the association between parasympathetic reactivity and working memory performance in adults reporting high levels of life stress

PubMed Central

Giuliano, Ryan J.; Gatzke-Kopp, Lisa M.; Roos, Leslie E.; Skowron, Elizabeth A.

2017-01-01

The neurovisceral integration model stipulates that autonomic function plays a critical role in the regulation of higher-order cognitive processes, yet most work to date has examined parasympathetic function in isolation from sympathetic function. Furthermore, the majority of work has been conducted on normative samples, which typically demonstrate parasympathetic withdrawal to increase arousal needed to complete cognitive tasks. Little is known about how autonomic regulation supports cognitive function in populations exposed to high levels of stress, which is critical given that chronic stress exposure alters autonomic function. To address this, we sought to characterize how parasympathetic (high-frequency heart rate variability, HF-HRV) and sympathetic (preejection period, PEP) measures of cardiac function contribute to individual differences in working memory (WM) capacity in a sample of high-risk women. HF-HRV and PEP were measured at rest and during a visual change detection measure of WM. Multilevel modeling was used to examine within-person fluctuations in WM performance throughout the task concurrently with HF-HRV and PEP, as well as between-person differences as a function of resting HF-HRV and PEP levels. Results indicate that resting PEP moderated the association between HF-HRV reactivity and WM capacity. Increases in WM capacity across the task were associated with increases in parasympathetic activity, but only among individuals with longer resting PEP (lower sympathetic arousal). Follow-up analyses showed that shorter resting PEP was associated with greater cumulative risk exposure. These results support the autonomic space framework, in that the relationship between behavior and parasympathetic function appears dependent on resting sympathetic activation. PMID:28449242

Distinguishing bipolar II depression from unipolar major depressive disorder: Differences in heart rate variability.

PubMed

Chang, Hsin-An; Chang, Chuan-Chia; Kuo, Terry B J; Huang, San-Yuan

2015-01-01

Bipolar II (BPII) depression is commonly misdiagnosed as unipolar depression (UD); however, an objective and reliable tool to differentiate between these disorders is lacking. Whether cardiac autonomic function can be used as a biomarker to distinguish BPII from UD is unknown. We recruited 116 and 591 physically healthy patients with BPII depression and UD, respectively, and 421 healthy volunteers aged 20-65 years. Interviewer and self-reported measures of depression/anxiety severity were obtained. Cardiac autonomic function was evaluated by heart rate variability (HRV) and frequency-domain indices of HRV. Patients with BPII depression exhibited significantly lower mean R-R intervals, variance (total HRV), low frequency (LF)-HRV, and high frequency (HF)-HRV but higher LF/HF ratio compared to those with UD. The significant differences remained after adjusting for age. Compared to the controls, the patients with BPII depression showed cardiac sympathetic excitation with reciprocal vagal impairment, whereas the UD patients showed only vagal impairment. Depression severity independently contributed to decreased HRV and vagal tone in both the patients with BPII depression and UD, but increased sympathetic tone only in those with BPII depression. HRV may aid in the differential diagnosis of BPII depression and UD as an adjunct to diagnostic interviews.

The sympathetic hazards of airborne ultrasound on ultrasound sensitive mice.

PubMed

Ohmori, M; Ogawa, K

1982-01-01

A commercially available ultrasonic equipment (55-50 kHz/sec, 425 W) operated at a distance of 4 m air space caused death in some mice. The physical energy propagated was quite small, being calculated at less than 0.21 W/cm2. Among many strains of mice, the RIII strain was especially sensitive to ultrasound, and the peak of sensitivity was at 3 to 4 weeks of age at which the mortality rate was 95/149 (64%). No death occurred when mice were pretreated by (a) removing all body hair, (b) by administration of morphine hydrochloridum with a tail reaction, and (c) administration of a sympathetic blocking agent. From these results it is assumed that the ultrasound energy absorbed by the body fur reaches the hypothalamus through the sensory nerves of the hair roots. After the hypothalamus where central sympathetic nerve functions are localized, the stimulus passes down the descending tract of the sympathetic nerve, reaching the cardiac nerves via the autonomic nerve ganglion. Thus, death could occur by shock of the sympathetic nerve reflex.

Remodelling of cardiac sympathetic re-innervation with thoracic spinal cord stimulation improves left ventricular function in a porcine model of heart failure.

PubMed

Liao, Song-Yan; Liu, Yuan; Zuo, Mingliang; Zhang, Yuelin; Yue, Wensheng; Au, Ka-Wing; Lai, Wing-Hon; Wu, Yangsong; Shuto, Chika; Chen, Peter; Siu, Chung-Wah; Schwartz, Peter J; Tse, Hung-Fat

2015-12-01

Thoracic spinal cord stimulation (SCS) has been shown to improve left ventricular ejection fraction (LVEF) in heart failure (HF). Nevertheless, the optimal duration (intermittent vs. continuous) of stimulation and the mechanisms of action remain unclear. We performed chronic thoracic SCS at the level of T1-T3 (50 Hz, pulse width 0.2 ms) in 30 adult pigs with HF induced by myocardial infarction and rapid ventricular pacing for 4 weeks. All the animals were treated with daily oral metoprolol succinate (25 mg) plus ramipril (2.5 mg), and randomized to a control group (n = 10), intermittent SCS (4 h ×3, n = 10) or continuous SCS (24 h, n = 10) for 10 weeks. Serial measurements of LVEF and +dP/dt and serum levels of norepinephrine and B-type natriuretic peptide (BNP) were measured. After sacrifice, immunohistological studies of myocardial sympathetic and parasympathetic nerve sprouting and innervation were performed. Echocardiogram revealed a significant increase in LVEF and +dP/dt at 10 weeks in both the intermittent and continuous SCS group compared with controls (P < 0.05). In both SCS groups, there was diffuse sympathetic nerve sprouting over the infarct, peri-infarct, and normal regions compared with only the peri-infarct and infarct regions in the control group. In addition, sympathetic innervation at the peri-infarct and infarct regions was increased following SCS, but decreased in the control group. Myocardium norepinephrine spillover and serum BNP at 10 weeks was significantly decreased only in the continuous SCS group (P < 0.05). In a porcine model of HF, SCS induces significant remodelling of cardiac sympathetic innervation over the peri-infarct and infarct regions and is associated with improved LV function and reduced myocardial norepinephrine spillover. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

Measuring Cardiac Autonomic Nervous System (ANS) Activity in Toddlers - Resting and Developmental Challenges.

PubMed

Bush, Nicole R; Caron, Zoe K; Blackburn, Katherine S; Alkon, Abbey

2016-02-25

The autonomic nervous system (ANS) consists of two branches, the parasympathetic and sympathetic nervous systems, and controls the function of internal organs (e.g., heart rate, respiration, digestion) and responds to everyday and adverse experiences (1). ANS measures in children have been found to be related to behavior problems, emotion regulation, and health (2-7). Therefore, understanding the factors that affect ANS development during early childhood is important. Both branches of the ANS affect young children's cardiovascular responses to stimuli and have been measured noninvasively, via external monitoring equipment, using valid and reliable measures of physiological change (8-11). However, there are few studies of very young children with simultaneous measures of the parasympathetic and sympathetic nervous systems, which limits understanding of the integrated functioning of the two systems. In addition, the majority of existing studies of young children report on infants' resting ANS measures or their reactivity to commonly used mother-child interaction paradigms, and less is known about ANS reactivity to other challenging conditions. We present a study design and standardized protocol for a non-invasive and rapid assessment of cardiac autonomic control in 18 month old children. We describe methods for continuous monitoring of the parasympathetic and sympathetic branches of the ANS under resting and challenge conditions during a home or laboratory visit and provide descriptive findings from our sample of 140 ethnically diverse toddlers using validated equipment and scoring software. Results revealed that this protocol can produce a range of physiological responses to both resting and developmentally challenging conditions, as indicated by changes in heart rate and indices of parasympathetic and sympathetic activity. Individuals demonstrated variability in resting levels, responses to challenges, and challenge reactivity, which provides additional evidence that this protocol is useful for the examination of ANS individual differences for toddlers.

Impact of aging on cardiac function in a female rat model of menopause: role of autonomic control, inflammation, and oxidative stress.

PubMed

Machi, Jacqueline Freire; Dias, Danielle da Silva; Freitas, Sarah Cristina; de Moraes, Oscar Albuquerque; da Silva, Maikon Barbosa; Cruz, Paula Lázara; Mostarda, Cristiano; Salemi, Vera M C; Morris, Mariana; De Angelis, Kátia; Irigoyen, Maria-Cláudia

2016-01-01

The aim of this study was to evaluate the effects of aging on metabolic, cardiovascular, autonomic, inflammatory, and oxidative stress parameters after ovarian hormone deprivation (OVX). Female Wistar rats (3 or 22 months old) were divided into: young controls, young ovariectomized, old controls, and old ovariectomized (bilateral ovaries removal). After a 9-week follow-up, physical capacity, metabolic parameters, and morphometric and cardiac functions were assessed. Subsequently, arterial pressure was recorded and cardiac autonomic control was evaluated. Oxidative stress was measured on the cardiac tissue, while inflammatory profile was assessed in the plasma. Aging or OVX caused an increase in body and fat weight and triglyceride concentration and a decrease in both insulin sensitivity and aerobic exercise capacity. Left ventricular diastolic dysfunction and increased cardiac overload (myocardial performance index) were reported in old groups when compared with young groups. Aging and OVX led to an increased sympathetic tonus, and vagal tonus was lower only for the old groups. Tumor necrosis factor-α and interleukin-6 were increased in old groups when compared with young groups. Glutathione redox balance (GSH/GSSG) was reduced in young ovariectomized, old controls, and old ovariectomized groups when compared with young controls, indicating an increased oxidative stress. A negative correlation was found between GSH/GSSG and tumor necrosis factor-α (r=-0.6, P<0.003). Correlations were found between interleukin-6 with adipose tissue (r=0.5, P<0.009) and vagal tonus (r=-0.7, P<0.0002); and among myocardial performance index with interleukin-6 (r=0.65, P<0.0002), sympathetic tonus (r=0.55, P<0.006), and physical capacity (r=-0.55, P<0.003). The findings in this trial showed that ovariectomy aggravated the impairment of cardiac and functional effects of aging in female rats, probably associated with exacerbated autonomic dysfunction, inflammation, and oxidative stress.

Bursting into space: alterations of sympathetic control by space travel

NASA Technical Reports Server (NTRS)

Eckberg, D. L.

2003-01-01

AIM: Astronauts return to Earth with reduced red cell masses and hypovolaemia. Not surprisingly, when they stand, their heart rates may speed inordinately, their blood pressures may fall, and some may experience frank syncope. We studied autonomic function in six male astronauts (average +/- SEM age: 40 +/- 2 years) before, during, and after the 16-day Neurolab space shuttle mission. METHOD: We recorded electrocardiograms, finger photoplethysmographic arterial pressures, respiration, peroneal nerve muscle sympathetic activity, plasma noradrenaline and noradrenaline kinetics, and cardiac output, and we calculated stroke volume and total peripheral resistance. We perturbed autonomic function before and during spaceflight with graded Valsalva manoeuvres and lower body suction, and before and after the mission with passive upright tilt. RESULTS: In-flight baseline sympathetic nerve activity was increased above pre-flight levels (by 10-33%) in three subjects, in whom noradrenaline spillover and clearance also were increased. Valsalva straining provoked greater reductions of arterial pressure, and proportionally greater sympathetic responses in space than on Earth. Lower body suction elicited greater increases of sympathetic nerve activity, plasma noradrenaline, and noradrenaline spillover in space than on Earth. After the Neurolab mission, left ventricular stroke volume was lower and heart rate was higher during tilt, than before spaceflight. No astronaut experienced orthostatic hypotension or pre-syncope during 10 min of post-flight tilting. CONCLUSION: We conclude that baseline sympathetic outflow, however measured, is higher in space than on earth, and that augmented sympathetic nerve responses to Valsalva straining, lower body suction, and post-flight upright tilt represent normal adjustments to greater haemodynamic stresses associated with hypovolaemia.

Ketamine-induced ventricular structural, sympathetic and electrophysiological remodelling: pathological consequences and protective effects of metoprolol

PubMed Central

Li, Y; Shi, J; Yang, BF; Liu, L; Han, CL; Li, WM; Dong, DL; Pan, ZW; Liu, GZ; Geng, JQ; Sheng, L; Tan, XY; Sun, DH; Gong, ZH; Gong, YT

2012-01-01

BACKGROUND AND PURPOSE Growing evidence suggests that long-term abuse of ketamine does harm the heart and increases the risk of sudden death. The present study was performed to explore the cardiotoxicity of ketamine and the protective effects of metoprolol. EXPERIMENTAL APPROACH Rats and rabbits were divided into control, ketamine, metoprolol alone and ketamine plus metoprolol groups. Ketamine (40 mg·kg−1·day−1, i.p.) and metoprolol (20 mg·kg−1·day−1, p.o.) were administered continuously for 12 weeks in rats and 8 weeks in rabbits. Cardiac function, electrophysiological disturbances, cardiac collagen, cardiomyocte apoptosis and the remodelling-related proteins were evaluated. KEY RESULTS Rabbits treated with ketamine showed decreased left ventricular ejection fraction, slowed ventricular conduction velocity and increased susceptibility to ventricular arrhythmia. Metoprolol prevented these pathophysiological alterations. In ketamine-treated rats, cardiac collagen volume fraction and apoptotic cell number were higher than those of control animals; these effects were prevented by co-administration of metoprolol. Consistently, the expressions of poly (ADP-ribose) polymerases-1, apoptosis-inducing factor and NF-κB-light-chain-enhancer of activated B cells were all increased after ketamine treatment and sharply reduced after metoprolol administration. Moreover, ketamine enhanced sympathetic sprouting, manifested as increased growth-associated protein 43 and tyrosine TH expression. These effects of ketamine were prevented by metoprolol. CONCLUSIONS AND IMPLICATIONS Chronic treatment with ketamine caused significant ventricular myocardial apoptosis, fibrosis and sympathetic sprouting, which altered the electrophysiological properties of the heart and increased its susceptibility to malignant arrhythmia that may lead to sudden cardiac death. Metoprolol prevented the cardiotoxicity of ketamine, indicating a promising new therapeutic strategy. PMID:21883145

Heart rate variability in newborns.

PubMed

Javorka, K; Lehotska, Z; Kozar, M; Uhrikova, Z; Kolarovszki, B; Javorka, M; Zibolen, M

2017-09-22

Heart rate (HR) and heart rate variability (HRV) in newborns is influenced by genetic determinants, gestational and postnatal age, and other variables. Premature infants have a reduced HRV. In neonatal HRV evaluated by spectral analysis, a dominant activity can be found in low frequency (LF) band (combined parasympathetic and sympathetic component). During the first postnatal days the activity in the high frequency (HF) band (parasympathetic component) rises, together with an increase in LF band and total HRV. Hypotrophy in newborn can cause less mature autonomic cardiac control with a higher contribution of sympathetic activity to HRV as demonstrated by sequence plot analysis. During quiet sleep (QS) in newborns HF oscillations increase - a phenomenon less expressed or missing in premature infants. In active sleep (AS), HRV is enhanced in contrast to reduced activity in HF band due to the rise of spectral activity in LF band. Comparison of the HR and HRV in newborns born by physiological vaginal delivery, without (VD) and with epidural anesthesia (EDA) and via sectio cesarea (SC) showed no significant differences in HR and in HRV time domain parameters. Analysis in the frequency domain revealed, that the lowest sympathetic activity in chronotropic cardiac chronotropic regulation is in the VD group. Different neonatal pathological states can be associated with a reduction of HRV and an improvement in the health conditions is followed by changes in HRV what can be use as a possible prognostic marker. Examination of heart rate variability in neonatology can provide information on the maturity of the cardiac chronotropic regulation in early postnatal life, on postnatal adaptation and in pathological conditions about the potential dysregulation of cardiac function in newborns, especially in preterm infants.

Cardiac autonomic function in children with type 1 diabetes.

PubMed

Metwalley, Kotb Abbass; Hamed, Sherifa Ahmed; Farghaly, Hekma Saad

2018-06-01

Cardiovascular autonomic neuropathy (CAN) is a major complication of type 1 diabetes (T1D). This study aimed to evaluate cardiac autonomic nervous system (ANS) function in children with T1D and its relation to different demographic, clinical and laboratory variable. This cross-sectional study included 60 children with T1D (mean age = 15.1 ± 3.3 years; duration of diabetes = 7.95 ± 3.83 years). The following 8 non-invasive autonomic testing were used for evaluation: heart rate at rest and in response to active standing (30:15 ratio), deep breathing and Valsalva maneuver (indicating parasympathetic function); blood pressure response to standing (orthostatic hypotension or OH), sustained handgrip and cold; and heart rate response to standing or positional orthostatic tachycardia syndrome or POTs (indicating sympathetic function). None had clinically manifest CAN. Compared to healthy children (5%), 36.67% of children with T1D had ≥ 2 abnormal tests (i.e., CAN) (P = 0.0001) which included significantly abnormal heart rate response to standing (POTs) (P = 0.052), active standing (30:15 ratio) (P = 0.0001) and Valsalva maneuver (P = 0.0001), indicating parasympathetic autonomic dysfunction, and blood pressure response to cold (P = 0.01), indicating sympathetic autonomic dysfunction. 54.55, 27.27 and 18.18% had early, definite and severe dysfunction of ANS. All patients had sensorimotor peripheral neuropathy. The longer duration of diabetes (> 5 years), presence of diabetic complications and worse glycemic control were significantly associated with CAN. The study concluded that both parasympathetic and sympathetic autonomic dysfunctions are common in children with T1D particularly with longer duration of diabetes and presence of microvascular complications. What is Known: • Cardiovascular autonomic neuropathy (CAN) is a major complication of type 1 diabetes (T1D). • Limited studies evaluated CAN in children with T1D. What is New: • CAN is common in children with T1D. • Cardiac autonomic functions should be assessed in children with T1D particularly in presence of microvascular complications.

Regular physical exercise improves cardiac autonomic and muscle vasodilatory responses to isometric exercise in healthy elderly.

PubMed

Sarmento, Adriana de Oliveira; Santos, Amilton da Cruz; Trombetta, Ivani Credidio; Dantas, Marciano Moacir; Oliveira Marques, Ana Cristina; do Nascimento, Leone Severino; Barbosa, Bruno Teixeira; Dos Santos, Marcelo Rodrigues; Andrade, Maria do Amparo; Jaguaribe-Lima, Anna Myrna; Brasileiro-Santos, Maria do Socorro

2017-01-01

The objective of this study was to evaluate cardiac autonomic control and muscle vasodilation response during isometric exercise in sedentary and physically active older adults. Twenty healthy participants, 10 sedentary and 10 physically active older adults, were evaluated and paired by gender, age, and body mass index. Sympathetic and parasympathetic cardiac activity (spectral and symbolic heart rate analysis) and muscle blood flow (venous occlusion plethysmography) were measured for 10 minutes at rest (baseline) and during 3 minutes of isometric handgrip exercise at 30% of the maximum voluntary contraction (sympathetic excitatory maneuver). Variables were analyzed at baseline and during 3 minutes of isometric exercise. Cardiac autonomic parameters were analyzed by Wilcoxon and Mann-Whitney tests. Muscle vasodilatory response was analyzed by repeated-measures analysis of variance followed by Tukey's post hoc test. Sedentary older adults had higher cardiac sympathetic activity compared to physically active older adult subjects at baseline (63.13±3.31 vs 50.45±3.55 nu, P =0.02). The variance (heart rate variability index) was increased in active older adults (1,438.64±448.90 vs 1,402.92±385.14 ms, P =0.02), and cardiac sympathetic activity (symbolic analysis) was increased in sedentary older adults (5,660.91±1,626.72 vs 4,381.35±1,852.87, P =0.03) during isometric handgrip exercise. Sedentary older adults showed higher cardiac sympathetic activity (spectral analysis) (71.29±4.40 vs 58.30±3.50 nu, P =0.03) and lower parasympathetic modulation (28.79±4.37 vs 41.77±3.47 nu, P =0.03) compared to physically active older adult subjects during isometric handgrip exercise. Regarding muscle vasodilation response, there was an increase in the skeletal muscle blood flow in the second (4.1±0.5 vs 3.7±0.4 mL/min per 100 mL, P =0.01) and third minute (4.4±0.4 vs 3.9±0.3 mL/min per 100 mL, P =0.03) of handgrip exercise in active older adults. The results indicate that regular physical activity improves neurovascular control of muscle blood flow and cardiac autonomic response during isometric handgrip exercise in healthy older adult subjects.

Regular physical exercise improves cardiac autonomic and muscle vasodilatory responses to isometric exercise in healthy elderly

PubMed Central

Sarmento, Adriana de Oliveira; Santos, Amilton da Cruz; Trombetta, Ivani Credidio; Dantas, Marciano Moacir; Oliveira Marques, Ana Cristina; do Nascimento, Leone Severino; Barbosa, Bruno Teixeira; Dos Santos, Marcelo Rodrigues; Andrade, Maria do Amparo; Jaguaribe-Lima, Anna Myrna; Brasileiro-Santos, Maria do Socorro

2017-01-01

The objective of this study was to evaluate cardiac autonomic control and muscle vasodilation response during isometric exercise in sedentary and physically active older adults. Twenty healthy participants, 10 sedentary and 10 physically active older adults, were evaluated and paired by gender, age, and body mass index. Sympathetic and parasympathetic cardiac activity (spectral and symbolic heart rate analysis) and muscle blood flow (venous occlusion plethysmography) were measured for 10 minutes at rest (baseline) and during 3 minutes of isometric handgrip exercise at 30% of the maximum voluntary contraction (sympathetic excitatory maneuver). Variables were analyzed at baseline and during 3 minutes of isometric exercise. Cardiac autonomic parameters were analyzed by Wilcoxon and Mann–Whitney tests. Muscle vasodilatory response was analyzed by repeated-measures analysis of variance followed by Tukey’s post hoc test. Sedentary older adults had higher cardiac sympathetic activity compared to physically active older adult subjects at baseline (63.13±3.31 vs 50.45±3.55 nu, P=0.02). The variance (heart rate variability index) was increased in active older adults (1,438.64±448.90 vs 1,402.92±385.14 ms, P=0.02), and cardiac sympathetic activity (symbolic analysis) was increased in sedentary older adults (5,660.91±1,626.72 vs 4,381.35±1,852.87, P=0.03) during isometric handgrip exercise. Sedentary older adults showed higher cardiac sympathetic activity (spectral analysis) (71.29±4.40 vs 58.30±3.50 nu, P=0.03) and lower parasympathetic modulation (28.79±4.37 vs 41.77±3.47 nu, P=0.03) compared to physically active older adult subjects during isometric handgrip exercise. Regarding muscle vasodilation response, there was an increase in the skeletal muscle blood flow in the second (4.1±0.5 vs 3.7±0.4 mL/min per 100 mL, P=0.01) and third minute (4.4±0.4 vs 3.9±0.3 mL/min per 100 mL, P=0.03) of handgrip exercise in active older adults. The results indicate that regular physical activity improves neurovascular control of muscle blood flow and cardiac autonomic response during isometric handgrip exercise in healthy older adult subjects. PMID:28721030

Effects of pacing-induced myocardial stress and spinal cord stimulation on whole body and cardiac norepinephrine spillover.

PubMed

Norrsell, H; Eliasson, T; Mannheimer, C; Augustinsson, L E; Bergh, C H; Andersson, B; Waagstein, F; Friberg, P

1997-12-01

Spinal cord stimulation has been used in the treatment of intractable angina pectoris since the beginning of the 1980s. This study was designed to investigate whether the documented anti-ischaemic effects of spinal cord stimulation are mediated through a decrease in sympathetic activity. Ten patients with a spinal cord stimulator implanted as anti-anginal treatment were included in the study. Atrial pacing until the patient experienced moderate angina was performed and after 50 min rest the procedure was repeated during spinal cord stimulation. Total body and cardiac norepinephrine spillover was calculated and the former was found to have increased during pacing (47%, P = 0.02). When spinal cord stimulation was applied, total body norepinephrine spillover decreased at a comparable pacing rate (18%, P = 0.02). Cardiac norepinephrine spillover was not affected during the procedure. The results of this study indicate that the anti-ischaemic effect of spinal cord stimulation is not due to reduced cardiac sympathetic activity. However, spinal cord stimulation decreases overall sympathetic activity which may benefit the heart, possibly by reducing oxygen demand.

Renal sympathetic denervation suppresses atrial fibrillation induced by acute atrial ischemia/infarction through inhibition of cardiac sympathetic activity.

PubMed

Zhou, Qina; Zhou, Xianhui; TuEr-Hong, ZuKe-la; Wang, Hongli; Yin, Tingting; Li, Yaodong; Zhang, Ling; Lu, Yanmei; Xing, Qiang; Zhang, Jianghua; Yang, Yining; Tang, Baopeng

2016-01-15

This study aims to explore the effects of renal sympathetic denervation (RSD) on atrial fibrillation (AF) inducibility and sympathetic activity induced by acute atrial ischemia/infarction. Acute ischemia/infarction was induced in 12 beagle dogs by ligating coronary arteries that supply the atria. Six dogs in the sham-RSD group did not undergo RSD, and six dogs without coronary artery ligation served as controls. AF induction rate, sympathetic discharge, catecholamine concentration and densities of tyrosine hydroxylase-positive nerves were measured. Acute atrial ischemia/infarction resulted in a significant increase of AF induction rate, which was decreased by RSD compared to controls (P<0.05). The root-mean-square peak value, peak area and number of sympathetic discharges were significantly augmented by atrial ischemia relative to the baseline and control (P<0.05). The number of sympathetic discharges was significantly reduced in the RSD group, compared to the control and sham-RSD groups (P<0.05). Norepinephrine and epinephrine concentrations in the atria, ventricle and kidney were elevated by atrial ischemia/infarction, but were reduced by RSD (P<0.05). Sympathetic hyperactivity was associated with pacing-induced AF after acute atrial ischemia/infarction. RSD has the potential to reduce the incidence of new-onset AF after acute atrial ischemia/infarction. The inhibition of cardiac sympathetic activity by RSD may be one of the major underlying mechanisms for the marked reduction of AF inducibility. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

A Nonsynonymous Polymorphism in Semaphorin 3A as a Risk Factor for Human Unexplained Cardiac Arrest with Documented Ventricular Fibrillation

PubMed Central

Nakano, Yukiko; Chayama, Kazuaki; Ochi, Hidenori; Toshishige, Masaaki; Hayashida, Yasufumi; Miki, Daiki; Hayes, C. Nelson; Suzuki, Hidekazu; Tokuyama, Takehito; Oda, Noboru; Suenari, Kazuyoshi; Uchimura-Makita, Yuko; Kajihara, Kenta; Sairaku, Akinori; Motoda, Chikaaki; Fujiwara, Mai; Watanabe, Yoshikazu; Yoshida, Yukihiko; Ohkubo, Kimie; Watanabe, Ichiro; Nogami, Akihiko; Hasegawa, Kanae; Watanabe, Hiroshi; Endo, Naoto; Aiba, Takeshi; Shimizu, Wataru; Ohno, Seiko; Horie, Minoru; Arihiro, Koji; Tashiro, Satoshi; Makita, Naomasa; Kihara, Yasuki

2013-01-01

Unexplained cardiac arrest (UCA) with documented ventricular fibrillation (VF) is a major cause of sudden cardiac death. Abnormal sympathetic innervations have been shown to be a trigger of ventricular fibrillation. Further, adequate expression of SEMA3A was reported to be critical for normal patterning of cardiac sympathetic innervation. We investigated the relevance of the semaphorin 3A (SEMA3A) gene located at chromosome 5 in the etiology of UCA. Eighty-three Japanese patients diagnosed with UCA and 2,958 healthy controls from two different geographic regions in Japan were enrolled. A nonsynonymous polymorphism (I334V, rs138694505A>G) in exon 10 of the SEMA3A gene identified through resequencing was significantly associated with UCA (combined P = 0.0004, OR 3.08, 95%CI 1.67–5.7). Overall, 15.7% of UCA patients carried the risk genotype G, whereas only 5.6% did in controls. In patients with SEMA3A I334V, VF predominantly occurred at rest during the night. They showed sinus bradycardia, and their RR intervals on the 12-lead electrocardiography tended to be longer than those in patients without SEMA3A I334V (1031±111 ms versus 932±182 ms, P = 0.039). Immunofluorescence staining of cardiac biopsy specimens revealed that sympathetic nerves, which are absent in the subendocardial layer in normal hearts, extended to the subendocardial layer only in patients with SEMA3A I334V. Functional analyses revealed that the axon-repelling and axon-collapsing activities of mutant SEMA3A I334V genes were significantly weaker than those of wild-type SEMA3A genes. A high incidence of SEMA3A I334V in UCA patients and inappropriate innervation patterning in their hearts implicate involvement of the SEMA3A gene in the pathogenesis of UCA. PMID:23593010

Cardiovascular consequences of sympathetic hyperactivity.

PubMed

Leenen, F H

1999-03-01

The sympathetic nervous system plays an integral role in many aspects of cardiovascular homeostasis. However, intermittent or chronic sympathetic hyperactivity can also initiate or accelerate cardiovascular pathology and provoke clinical events in the presence of cardiovascular disease. Both alpha- and beta-receptors mediate these responses. In the case of the heart, alpha- and beta- receptors contribute to ventricular arrhythmias and cardiac hypertrophy. Moreover, cardiac beta2-receptors mediate not only chronotropic and inotropic responses at the postsynaptic level, but also noradrenalin release at the presynaptic level. To block the adverse effects of sympathetic hyperactivity optimally, one would therefore need both alpha- and nonselective beta-receptor blockade. On the other hand, prevention or reversal of sympathetic hyperactivity at the central level appears to be an attractive alternative. Alpha2-agonists such as clonidine and alpha-methyldopa are clearly effective in this regard but are associated with side effects. More recent research indicates that in the central nervous systen (CNS) other classes such as dihydropyridines (eg, nifedipine) or angiotensin II type 1 receptor blockers (eg, losartan) also can decrease elevated sympathetic nerve activity. The therapeutic relevance of these CNS effects and differences between lipophilic and hydrophilic compounds provide intriguing new avenues for research in disorders such as hypertension and congestive heart failure.

Cardiac regulation in the socially monogamous prairie vole

PubMed Central

Grippo, Angela J.; Lamb, Damon G.; Carter, C. Sue; Porges, Stephen W.

2007-01-01

Social experiences, both positive and negative, may influence cardiovascular regulation. Prairie voles (Microtus ochrogaster) are socially monogamous rodents that form social bonds similar to those seen in primates, and this species may provide a useful model for investigating neural and social regulation of cardiac function. Cardiac regulation has not been studied previously in the prairie vole. Radiotelemetry transmitters were implanted into adult female prairie voles under anesthesia, and electrocardiographic parameters were recorded. Autonomic blockade was performed using atenolol (8 mg/kg ip) and atropine methyl nitrate (4 mg/kg ip). Several variables were evaluated, including heart rate (HR), HR variability and the amplitude of respiratory sinus arrhythmia. Sympathetic blockade significantly reduced HR. Parasympathetic blockade significantly increased HR, and reduced HR variability and the amplitude of respiratory sinus arrhythmia. Combined autonomic blockade significantly increased HR, and reduced HR variability and respiratory sinus arrhythmia amplitude. The data indicate that autonomic function in prairie voles shares similarities with primates, with a predominant vagal influence on cardiac regulation. The current results provide a foundation for studying neural and social regulation of cardiac function during different behavioral states in this socially monogamous rodent model. PMID:17107695

Effects of percutaneous renal sympathetic denervation on cardiac function and exercise tolerance in patients with chronic heart failure.

PubMed

Gao, Jun-Qing; Xie, Yun; Yang, Wei; Zheng, Jian-Pu; Liu, Zong-Jun

2017-01-01

Sympathetic hyperactivity, a vital factor in the genesis and development of heart failure (HF), has been reported to be effectively reduced by percutaneous renal denervation (RDN), which may play an important role in HF treatment. To determine the effects of percutaneous RDN on cardiac function in patients with chronic HF (CHF). Fourteen patients (mean age 69.6 years; ejection fraction [EF] <45%) with CHF received bilateral RDN. Adverse cardiac events, blood pressure (BP), and biochemical parameters were assessed before and six months after percutaneous operation. Patients also underwent echocardiographic assessment of cardiac function and 6-min walk test before and at six months after percutaneous operation. The distance achieved by the 14 patients in the 6-min walk test increased significantly from 152.9±38.0 m before RDN to 334.3±94.4 m at six months after RDN (p<0.001), while EF increased from 36.0±4.1% to 43.8±7.9% (p=0.003) on echocardiography. No RDN-related complications were observed during the follow-up period. In 6-month follow-up, systolic BP decreased from 138.6±22.1 mmHg to 123.2±10.5 mmHg (p=0.026) and diastolic BP from 81.1±11.3 mmHg to 72.9±7.5 mmHg (p=0.032). Creatinine levels did not change significantly (1.3±0.65 mg/dl to 1.2±0.5 mg/dl, p=0.8856). RDN is potentially an effective technique for the treatment of severe HF that can significantly increase EF and improve exercise tolerance. Copyright © 2016 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.

TNF-α receptor 1 knockdown in the subfornical organ ameliorates sympathetic excitation and cardiac hemodynamics in heart failure rats.

PubMed

Yu, Yang; Wei, Shun-Guang; Weiss, Robert M; Felder, Robert B

2017-10-01

In systolic heart failure (HF), circulating proinflammatory cytokines upregulate inflammation and renin-angiotensin system (RAS) activity in cardiovascular regions of the brain, contributing to sympathetic excitation and cardiac dysfunction. Important among these is the subfornical organ (SFO), a forebrain circumventricular organ that lacks an effective blood-brain barrier and senses circulating humors. We hypothesized that the tumor necrosis factor-α (TNF-α) receptor 1 (TNFR1) in the SFO contributes to sympathetic excitation and cardiac dysfunction in HF rats. Rats received SFO microinjections of a TNFR1 shRNA or a scrambled shRNA lentiviral vector carrying green fluorescent protein, or vehicle. One week later, some rats were euthanized to confirm the accuracy of the SFO microinjections and the transfection potential of the lentiviral vector. Other rats underwent coronary artery ligation (CL) to induce HF or a sham operation. Four weeks after CL, vehicle- and scrambled shRNA-treated HF rats had significant increases in TNFR1 mRNA and protein, NF-κB activity, and mRNA for inflammatory mediators, RAS components and c-Fos protein in the SFO and downstream in the hypothalamic paraventricular nucleus, along with increased plasma norepinephrine levels and impaired cardiac function, compared with vehicle-treated sham-operated rats. In HF rats treated with TNFR1 shRNA, TNFR1 was reduced in the SFO but not paraventricular nucleus, and the central and peripheral manifestations of HF were ameliorated. In sham-operated rats treated with TNFR1 shRNA, TNFR1 expression was also reduced in the SFO but there were no other effects. These results suggest a key role for TNFR1 in the SFO in the pathophysiology of systolic HF. NEW & NOTEWORTHY Activation of TNF-α receptor 1 in the subfornical organ (SFO) contributes to sympathetic excitation in heart failure rats by increasing inflammation and renin-angiotensin system activity in the SFO and downstream in the hypothalamic paraventricular nucleus. Cytokine receptors in the SFO may be a target for central intervention in cardiovascular conditions characterized by peripheral inflammation.

Focal Reduction in Cardiac 123I-Metaiodobenzylguanidine Uptake in Patients With Anderson-Fabry Disease.

PubMed

Yamamoto, Saori; Suzuki, Hideaki; Sugimura, Koichiro; Tatebe, Shunsuke; Aoki, Tatsuo; Miura, Masanobu; Yaoita, Nobuhiro; Sato, Haruka; Kozu, Katuya; Ota, Hideki; Takanami, Kentaro; Takase, Kei; Shimokawa, Hiroaki

2016-11-25

It remains to be elucidated whether cardiac sympathetic nervous activity is impaired in patients with Anderson-Fabry disease (AFD).Methods and Results:We performed 123 I-meta-iodobenzylguanidine (MIBG) scintigraphy and gadolinium-enhanced cardiovascular magnetic resonance (CMR) in 5 AFD patients. MIBG uptake in the inferolateral wall, where wall thinning and delayed enhancement were noted on CMR, was significantly lower compared with the anteroseptal wall. The localized reduction in MIBG uptake was also noted in 2 patients with no obvious abnormal findings on CMR. Cardiac sympathetic nervous activity is impaired in AFD before development of structural myocardial abnormalities. (Circ J 2016; 80: 2550-2551).

MURC/Cavin-4 facilitates recruitment of ERK to caveolae and concentric cardiac hypertrophy induced by α1-adrenergic receptors.

PubMed

Ogata, Takehiro; Naito, Daisuke; Nakanishi, Naohiko; Hayashi, Yukiko K; Taniguchi, Takuya; Miyagawa, Kotaro; Hamaoka, Tetsuro; Maruyama, Naoki; Matoba, Satoaki; Ikeda, Koji; Yamada, Hiroyuki; Oh, Hidemasa; Ueyama, Tomomi

2014-03-11

The actions of catecholamines on adrenergic receptors (ARs) induce sympathetic responses, and sustained activation of the sympathetic nervous system results in disrupted circulatory homeostasis. In cardiomyocytes, α1-ARs localize to flask-shaped membrane microdomains known as "caveolae." Caveolae require both caveolin and cavin proteins for their biogenesis and function. However, the functional roles and molecular interactions of caveolar components in cardiomyocytes are poorly understood. Here, we showed that muscle-restricted coiled-coil protein (MURC)/Cavin-4 regulated α1-AR-induced cardiomyocyte hypertrophy through enhancement of ERK1/2 activation in caveolae. MURC/Cavin-4 was expressed in the caveolae and T tubules of cardiomyocytes. MURC/Cavin-4 overexpression distended the caveolae, whereas MURC/Cavin-4 was not essential for their formation. MURC/Cavin-4 deficiency attenuated cardiac hypertrophy induced by α1-AR stimulation in the presence of caveolae. Interestingly, MURC/Cavin-4 bound to α1A- and α1B-ARs as well as ERK1/2 in caveolae, and spatiotemporally modulated MEK/ERK signaling in response to α1-AR stimulation. Thus, MURC/Cavin-4 facilitates ERK1/2 recruitment to caveolae and efficient α1-AR signaling mediated by caveolae in cardiomyocytes, which provides a unique insight into the molecular mechanisms underlying caveola-mediated signaling in cardiac hypertrophy.

MURC/Cavin-4 facilitates recruitment of ERK to caveolae and concentric cardiac hypertrophy induced by α1-adrenergic receptors

PubMed Central

Ogata, Takehiro; Naito, Daisuke; Nakanishi, Naohiko; Hayashi, Yukiko K.; Taniguchi, Takuya; Miyagawa, Kotaro; Hamaoka, Tetsuro; Maruyama, Naoki; Matoba, Satoaki; Ikeda, Koji; Yamada, Hiroyuki; Oh, Hidemasa; Ueyama, Tomomi

2014-01-01

The actions of catecholamines on adrenergic receptors (ARs) induce sympathetic responses, and sustained activation of the sympathetic nervous system results in disrupted circulatory homeostasis. In cardiomyocytes, α1-ARs localize to flask-shaped membrane microdomains known as “caveolae.” Caveolae require both caveolin and cavin proteins for their biogenesis and function. However, the functional roles and molecular interactions of caveolar components in cardiomyocytes are poorly understood. Here, we showed that muscle-restricted coiled-coil protein (MURC)/Cavin-4 regulated α1-AR–induced cardiomyocyte hypertrophy through enhancement of ERK1/2 activation in caveolae. MURC/Cavin-4 was expressed in the caveolae and T tubules of cardiomyocytes. MURC/Cavin-4 overexpression distended the caveolae, whereas MURC/Cavin-4 was not essential for their formation. MURC/Cavin-4 deficiency attenuated cardiac hypertrophy induced by α1-AR stimulation in the presence of caveolae. Interestingly, MURC/Cavin-4 bound to α1A- and α1B-ARs as well as ERK1/2 in caveolae, and spatiotemporally modulated MEK/ERK signaling in response to α1-AR stimulation. Thus, MURC/Cavin-4 facilitates ERK1/2 recruitment to caveolae and efficient α1-AR signaling mediated by caveolae in cardiomyocytes, which provides a unique insight into the molecular mechanisms underlying caveola-mediated signaling in cardiac hypertrophy. PMID:24567387

Exercise intolerance in Type 2 diabetes: is there a cardiovascular contribution?

PubMed

Poitras, Veronica J; Hudson, Robert W; Tschakovsky, Michael E

2018-05-01

Physical activity is critically important for Type 2 diabetes management, yet adherence levels are poor. This might be partly due to disproportionate exercise intolerance. Submaximal exercise tolerance is highly sensitive to muscle oxygenation; impairments in exercising muscle oxygen delivery may contribute to exercise intolerance in Type 2 diabetes since there is considerable evidence for the existence of both cardiac and peripheral vascular dysfunction. While uncompromised cardiac output during submaximal exercise is consistently observed in Type 2 diabetes, it remains to be determined whether an elevated cardiac sympathetic afferent reflex could sympathetically restrain exercising muscle blood flow. Furthermore, while deficits in endothelial function are common in Type 2 diabetes and are often cited as impairing exercising muscle oxygen delivery, no direct evidence in exercise exists, and there are several other vasoregulatory mechanisms whose dysfunction could contribute. Finally, while there are findings of impaired oxygen delivery, conflicting evidence also exists. A definitive conclusion that Type 2 diabetes compromises exercising muscle oxygen delivery remains premature. We review these potentially dysfunctional mechanisms in terms of how they could impair oxygen delivery in exercise, evaluate the current literature on whether an oxygen delivery deficit is actually manifest, and correspondingly identify key directions for future research.

Effect of autogenic training on cardiac autonomic nervous activity in high-risk fire service workers for posttraumatic stress disorder.

PubMed

Mitani, Satoko; Fujita, Masatoshi; Sakamoto, Satoko; Shirakawa, Taro

2006-05-01

We investigated the effect of autogenic training (AT) on cardiac autonomic nervous activity in fire services workers with the use of the questionnaire of the Japanese-language version of Impact of Event Scale-Revised (IES-R-J) and indexes of heart rate variability. We studied 22 male fire services workers who were divided into posttraumatic stress disorder (PTSD)-related stress group (n=10) and control group (n=12). They underwent AT twice or three times a week for 2 months. Posttraumatic stress disorder-related stress group showed a significantly higher cardiac sympathetic nervous activity and a significantly lower cardiac parasympathetic nervous activity than control group at baseline. Autogenic training significantly decreased cardiac sympathetic nervous activity and significantly increased cardiac parasympathetic nervous activity in both groups. These changes were accompanied by a significant decrease in the total points of IES-R-J. Autogenic training is effective for ameliorating the disturbance of cardiac autonomic nervous activity and psychological issues secondary to PTSD.

Effects of exercise training on cardiovascular adrenergic system.

PubMed

Leosco, Dario; Parisi, Valentina; Femminella, Grazia D; Formisano, Roberto; Petraglia, Laura; Allocca, Elena; Bonaduce, Domenico

2013-11-28

In heart failure (HF), exercise has been shown to modulate cardiac sympathetic hyperactivation which is one of the earliest features of neurohormonal derangement in this syndrome and correlates with adverse outcome. An important molecular alteration related to chronic sympathetic overstimulation in HF is represented by cardiac β-adrenergic receptor (β-AR) dysfunction. It has been demonstrated that exercise reverses β-AR dysfunction by restoring cardiac receptor membrane density and G-protein-dependent adenylyl cyclase activation. In particular, several evidence indicate that exercise reduces levels of cardiac G-protein coupled receptor kinase-2 (GRK2) which is known to be involved in both β1-AR and β2-AR dysregulation in HF. Similar alterations of β-AR system have been described also in the senescent heart. It has also been demonstrated that exercise training restores adrenal GRK2/α-2AR/catecholamine (CA) production axis. At vascular level, exercise shows a therapeutic effect on age-related impairment of vascular reactivity to adrenergic stimulation and restores β-AR-dependent vasodilatation by increasing vascular β-AR responsiveness and reducing endothelial GRK2 activity. Sympathetic nervous system overdrive is thought to account for >50% of all cases of hypertension and a lack of balance between parasympathetic and sympathetic modulation has been observed in hypertensive subjects. Non-pharmacological, lifestyle interventions have been associated with reductions in SNS overactivity and blood pressure in hypertension. Several evidence have highlighted the blood pressure lowering effects of aerobic endurance exercise in patients with hypertension and the significant reduction in sympathetic neural activity has been reported as one of the main mechanisms explaining the favorable effects of exercise on blood pressure control.

Update on the slow delayed rectifier potassium current (I(Ks)): role in modulating cardiac function.

PubMed

Liu, Zhenzhen; Du, Lupei; Li, Minyong

2012-01-01

The slow delayed rectifier current (I(Ks)) is the slow component of cardiac delayed rectifier current and is critical for the late phase repolarization of cardiac action potential. This current is also an important target for Sympathetic Nervous System (SNS) to regulate the cardiac electivity to accommodate to heart rate alterations in response to exercise or emotional stress and can be up-regulated by β- adrenergic or other signal molecules. I(Ks) channel is originated by the co-assembly of pore-forming KCNQ1 α-subunit and accessory KCNE1 β-subunit. Mutations in any subunit can bring about severe long QT syndrome (LQT-1, LQT-5) as characterized by deliquium, seizures and sudden death. This review summarizes the normal physiological functions and molecular basis of I(Ks) channels, as well as illustrates up-to-date development on its blockers and activators. Therefore, the current extensive survey should generate fundamental understanding of the role of I(Ks) channel in modulating cardiac function and donate some instructions to the progression of I(Ks) blockers and activators as potential antiarrhythmic agents or pharmacological tools to determine the physiological and pathological function of I(Ks).

Efficacy and Safety of Renal Sympathetic Denervation on Dogs with Pressure Overload-Induced Heart Failure.

PubMed

Chen, Pingan; Leng, Shuilong; Luo, Yishan; Li, Shaonan; Huang, Zicheng; Liu, Zhenxi; Liu, Zhen; Wang, Jie; Lei, Xiaoming

2017-02-01

In dogs with heart failure (HF) induced by overload pressure, the role of renal sympathetic denervation (RSD) on heart failure and in the renal artery is unclear. Therefore, we investigated the efficacy and safety of RSD in dogs with pressure overload-induced heart failure. Twenty mongrel dogs were divided into a sham-operated group, an HF group and an HF + RSD group. In the sham-operated group, the abdominal aorta was located but was not constricted, in the HF group, the abdominal aorta was constricted without RSD, and the HF+RSD group underwent RSD with constriction of the abdominal aorta after 10 weeks. Blood sampling assays, echocardiography, intravascular ultrasound (IVUS) measurement and histopathological examination were performed. Renal sympathetic denervation caused a significant reduction in the levels of noradrenaline (166.62±6.84 vs. 183.48±13.66 pg/ml, P<0.05), plasma renin activity (1.93±0.12 vs. 2.10±0.13 ng/mlh, P<0.05) and B-type natriuretic peptide (71.14±3.86 vs. 83.15±5.73 pg/ml, P<0.05) at eight weeks after RSD in the HF+RSD group. Compared with the HF group at eight weeks, the left ventricular internal dimension at end-diastole and end-systole were lower and the left ventricular ejection fraction was higher (all P<0.05) at eight weeks after RSD in the HF+RSD group. Intravenous ultrasound images showed no changes in the renal artery lumen, and intimal hyperplasia and vascular lumen stenosis were not observed after RSD. Renal sympathetic denervation could improve cardiac function in dogs with HF induced by pressure overload; RSD had no adverse influence on the renal artery. Copyright © 2016 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.

Developmental neurotoxicity targeting hepatic and cardiac sympathetic innervation: effects of organophosphates are distinct from those of glucocorticoids.

PubMed

Seidler, Frederic J; Slotkin, Theodore A

2011-05-30

Early-life exposure to organophosphate pesticides leads to subsequent hyperresponsiveness of β-adrenergic receptor-mediated cell signaling that regulates hepatic gluconeogenesis, culminating in metabolic abnormalities resembling prediabetes. In the current study, we evaluated the effects of chlorpyrifos or parathion on presynaptic sympathetic innervation to determine whether the postsynaptic signaling effects are accompanied by defects in neuronal input. We administered either chlorpyrifos or parathion to newborn rats using exposure paradigms known to elicit the later metabolic changes but found no alterations in either hepatic or cardiac norepinephrine levels in adolescence or adulthood. However, shifting chlorpyrifos exposure to the prenatal period did evoke changes: exposure early in gestation produced subsequent elevations in norepinephrine, whereas later gestational exposure produced significant deficits. We also distinguished the organophosphate effects from those of the glucocorticoid, dexamethasone, a known endocrine disruptor that leads to later-life metabolic and cardiovascular disruption. Postnatal exposure to dexamethasone elicited deficits in peripheral norepinephrine levels but prenatal exposure did not. Our results indicate that early-life exposure to organophosphates leads to subsequent abnormalities of peripheral sympathetic innervation through mechanisms entirely distinct from those of glucocorticoids, ruling out the possibility that the organophosphate effects are secondary to stress or disruption of the HPA axis. Further, the effects on innervation were separable from those on postsynaptic signaling, differing in critical period as well as tissue- and sex-selectivity. Organophosphate targeting of both presynaptic and postsynaptic β-adrenergic sites, each with different critical periods of vulnerability, thus sets the stage for compounding of hepatic and cardiac functional abnormalities. Copyright © 2011 Elsevier Inc. All rights reserved.

The low frequency power of heart rate variability is neither a measure of cardiac sympathetic tone nor of baroreflex sensitivity.

PubMed

Martelli, Davide; Silvani, Alessandro; McAllen, Robin M; May, Clive N; Ramchandra, Rohit

2014-10-01

The lack of noninvasive approaches to measure cardiac sympathetic nerve activity (CSNA) has driven the development of indirect estimates such as the low-frequency (LF) power of heart rate variability (HRV). Recently, it has been suggested that LF HRV can be used to estimate the baroreflex modulation of heart period (HP) rather than cardiac sympathetic tone. To test this hypothesis, we measured CSNA, HP, blood pressure (BP), and baroreflex sensitivity (BRS) of HP, estimated with the modified Oxford technique, in conscious sheep with pacing-induced heart failure and in healthy control sheep. We found that CSNA was higher and systolic BP and HP were lower in sheep with heart failure than in control sheep. Cross-correlation analysis showed that in each group, the beat-to-beat changes in HP correlated with those in CSNA and in BP, but LF HRV did not correlate significantly with either CSNA or BRS. However, when control sheep and sheep with heart failure were considered together, CSNA correlated negatively with HP and BRS. There was also a negative correlation between CSNA and BRS in control sheep when considered alone. In conclusion, we demonstrate that in conscious sheep, LF HRV is neither a robust index of CSNA nor of BRS and is outperformed by HP and BRS in tracking CSNA. These results do not support the use of LF HRV as a noninvasive estimate of either CSNA or baroreflex function, but they highlight a link between CSNA and BRS. Copyright © 2014 the American Physiological Society.

Gender Differences in Autonomic Control of the Cardiovascular System.

PubMed

Pothineni, Naga Venkata; Shirazi, Lily F; Mehta, Jawahar L

2016-01-01

The autonomic nervous system (ANS) is a key regulator of the cardiovascular system. The two arms of the ANS, sympathetic and parasympathetic (vagal) have co-regulatory effects on cardiac homeostasis. ANS modulation and dysfunction are also believed to affect various cardiac disease states. Over the past decade, there has been increasing evidence suggesting gender differences in ANS activity. In multiple previous studies, ANS activity was primarily assessed using heart rate variability, muscle sympathetic nerve activity, coronary blood flow velocity, and plasma biomarkers. Heart rate variability is a non-invasive measure, which can be analyzed in terms of low frequency and high frequency oscillations, which indicate the sympathetic and parasympathetic tone, respectively. These measures have been studied between women and men in states of rest and stress, and in cardiac disease. Studies support the concept of a significant gender difference in ANS activity. Further studies are indicated to elucidate specific differences and mechanisms, which could guide targeted therapy of various cardiovascular disease states.

Macaque Cardiac Physiology Is Sensitive to the Valence of Passively Viewed Sensory Stimuli

PubMed Central

Bliss-Moreau, Eliza; Machado, Christopher J.; Amaral, David G.

2013-01-01

Autonomic nervous system activity is an important component of affective experience. We demonstrate in the rhesus monkey that both the sympathetic and parasympathetic branches of the autonomic nervous system respond differentially to the affective valence of passively viewed video stimuli. We recorded cardiac impedance and an electrocardiogram while adult macaques watched a series of 300 30-second videos that varied in their affective content. We found that sympathetic activity (as measured by cardiac pre-ejection period) increased and parasympathetic activity (as measured by respiratory sinus arrhythmia) decreased as video content changes from positive to negative. These findings parallel the relationship between autonomic nervous system responsivity and valence of stimuli in humans. Given the relationship between human cardiac physiology and affective processing, these findings suggest that macaque cardiac physiology may be an index of affect in nonverbal animals. PMID:23940712

Long-term administration of pyridostigmine attenuates pressure overload-induced cardiac hypertrophy by inhibiting calcineurin signalling.

PubMed

Lu, Yi; Zhao, Ming; Liu, Jin-Jun; He, Xi; Yu, Xiao-Jiang; Liu, Long-Zhu; Sun, Lei; Chen, Li-Na; Zang, Wei-Jin

2017-09-01

Cardiac hypertrophy is associated with autonomic imbalance, characterized by enhanced sympathetic activity and withdrawal of parasympathetic control. Increased parasympathetic function improves ventricular performance. However, whether pyridostigmine, a reversible acetylcholinesterase inhibitor, can offset cardiac hypertrophy induced by pressure overload remains unclear. Hence, this study aimed to determine whether pyridostigmine can ameliorate pressure overload-induced cardiac hypertrophy and identify the underlying mechanisms. Rats were subjected to either sham or constriction of abdominal aorta surgery and treated with or without pyridostigmine for 8 weeks. Vagal activity and cardiac function were determined using PowerLab. Cardiac hypertrophy was evaluated using various histological stains. Protein markers for cardiac hypertrophy were quantitated by Western blot and immunoprecipitation. Pressure overload resulted in a marked reduction in vagal discharge and a profound increase in cardiac hypertrophy index and cardiac dysfunction. Pyridostigmine increased the acetylcholine levels by inhibiting acetylcholinesterase in rats with pressure overload. Pyridostigmine significantly attenuated cardiac hypertrophy based on reduction in left ventricular weight/body weight, suppression of the levels of atrial natriuretic peptide, brain natriuretic peptide and β-myosin heavy chain, and a reduction in cardiac fibrosis. These effects were accompanied by marked improvement of cardiac function. Additionally, pyridostigmine inhibited the CaN/NFAT3/GATA4 pathway and suppressed Orai1/STIM1 complex formation. In conclusion, pressure overload resulted in cardiac hypertrophy, cardiac dysfunction and a significant reduction in vagal discharge. Pyridostigmine attenuated cardiac hypertrophy and improved cardiac function, which was related to improved cholinergic transmission efficiency (decreased acetylcholinesterase and increased acetylcholine), inhibition of the CaN/NFAT3/GATA4 pathway and suppression of the interaction of Orai1/STIM1. © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Afferent fibres from pulmonary arterial baroreceptors in the left cardiac sympathetic nerve of the cat

PubMed Central

Nishi, K.; Sakanashi, M.; Takenaka, F.

1974-01-01

1. Afferent discharges were recorded from the left cardiac sympathetic nerve or the third sympathetic ramus communicans of anaesthetized cats. Twenty-one single units with baroreceptor activity were obtained. 2. The receptors of each unit were localized to the extrapulmonary part of the pulmonary artery, determined by direct mechanical probing of the wall of the pulmonary artery after death of the animals. Conduction velocity of the fibres ranged from 2·5 to 15·7 m/sec. 3. Afferent discharges occurred irregularly under artificial ventilation. The impulse activity was increased when pulmonary arterial pressure was raised by an intravenous infusion of Locke solution, or by occlusion of lung roots, and decreased by bleeding the animal from the femoral artery. 4. Above a threshold pressure, discharges occurred synchronously with the systolic pressure pulse in the pulmonary artery. A progressive further rise in pressure did not produce an increase in the number of impulses per heart beat. Occlusion of lung roots initially elicited a burst of discharges but the number of impulses for each cardiac cycle gradually decreased. 5. The receptors responded to repetitive mechanical stimuli up to a frequency of 10/sec, but failed to respond to stimuli delivered at 20/sec. 6. The results provide further evidence for the presence of afferent fibres in the cardiac sympathetic nerve. These afferent fibres are likely to provide the spinal cord with specific information only on transient changes in pulmonary arterial pressure. PMID:4850456

Changes in heart rate variability during anaesthesia induction using sevoflurane or isoflurane with nitrous oxide.

PubMed

Nishiyama, Tomoki

2016-01-01

The purpose of this study was to compare cardiac sympathetic and parasympathetic balance using heart rate variability (HRV) during induction of anaesthesia between sevoflurane and isoflurane in combination with nitrous oxide. 40 individuals aged from 30 to 60 years, scheduled for general anaesthesia were equally divided into sevoflurane or isoflurane groups. After 100% oxygen inhalation for a few minutes, anaesthesia was induced with nitrous oxide 3 L min-1, oxygen 3 L min-1 and sevoflurane or isoflurane. Sevoflurane or isoflurane concentration was increased by 0.5% every 2 to 3 breaths until 5% was attained for sevoflurane, or 3% for isoflurane. Vecuronium was administered to facilitate tracheal intubation. After intubation, sevoflurane was set to 2% while isoflurane was set to 1% with nitrous oxide with oxygen (1:1) for 5 min. Both sevoflurane and isoflurane provoked a decrease in blood pressure, total power, the low frequency component (LF), and high frequency component (HF) of HRV. Although the heart rate increased during isoflurane anaesthesia, it decreased under sevoflurane. The power of LF and HF also decreased in both groups. LF was higher in the isoflurane group while HF was higher in the sevoflurane group. The LF/HF ratio increased transiently in the isoflurane group, but decreased in the sevoflurane group. Anaesthesia induction with isoflurane-nitrous oxide transiently increased cardiac sympathetic activity, while sevoflurane-nitrous oxide decreased both cardiac sympathetic and parasympathetic activities. The balance of cardiac parasympathetic/sympathetic activity was higher in sevoflurane anaesthesia.

Effects of short-term continuous positive airway pressure on myocardial sympathetic nerve function and energetics in patients with heart failure and obstructive sleep apnea: a randomized study.

PubMed

Hall, Allison B; Ziadi, Maria C; Leech, Judith A; Chen, Shin-Yee; Burwash, Ian G; Renaud, Jennifer; deKemp, Robert A; Haddad, Haissam; Mielniczuk, Lisa M; Yoshinaga, Keiichiro; Guo, Ann; Chen, Li; Walter, Olga; Garrard, Linda; DaSilva, Jean N; Floras, John S; Beanlands, Rob S B

2014-09-09

Heart failure with reduced ejection fraction and obstructive sleep apnea (OSA), 2 states of increased metabolic demand and sympathetic nervous system activation, often coexist. Continuous positive airway pressure (CPAP), which alleviates OSA, can improve ventricular function. It is unknown whether this is due to altered oxidative metabolism or presynaptic sympathetic nerve function. We hypothesized that short-term (6-8 weeks) CPAP in patients with OSA and heart failure with reduced ejection fraction would improve myocardial sympathetic nerve function and energetics. Forty-five patients with OSA and heart failure with reduced ejection fraction (left ventricular ejection fraction 35.8±9.7% [mean±SD]) were evaluated with the use of echocardiography and 11C-acetate and 11C-hydroxyephedrine positron emission tomography before and ≈6 to 8 weeks after randomization to receive short-term CPAP (n=22) or no CPAP (n=23). Work metabolic index, an estimate of myocardial efficiency, was calculated as follows: (stroke volume index×heart rate×systolic blood pressure÷Kmono), where Kmono is the monoexponential function fit to the myocardial 11C-acetate time-activity data, reflecting oxidative metabolism. Presynaptic sympathetic nerve function was measured with the use of the 11C-hydroxyephedrine retention index. CPAP significantly increased hydroxyephedrine retention versus no CPAP (Δretention: +0.012 [0.002, 0.021] versus -0.006 [-0.013, 0.005] min(-1); P=0.003). There was no significant change in work metabolic index between groups. However, in those with more severe OSA (apnea-hypopnea index>20 events per hour), CPAP significantly increased both work metabolic index and systolic blood pressure (P<0.05). In patients with heart failure with reduced ejection fraction and OSA, short-term CPAP increased hydroxyephedrine retention, indicating improved myocardial sympathetic nerve function, but overall did not affect energetics. In those with more severe OSA, CPAP may improve cardiac efficiency. Further outcome-based investigation of the consequences of CPAP is warranted. http://www.clinicaltrials.gov. Unique identifier: NCT00756366. © 2014 American Heart Association, Inc.

Influence of cardiac nerve status on cardiovascular regulation and cardioprotection

PubMed Central

Kingma, John G; Simard, Denys; Rouleau, Jacques R

2017-01-01

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. PMID:28706586

Nonuniformity in the von Bezold-Jarisch reflex.

PubMed

Salo, Lauren M; Woods, Robyn L; Anderson, Colin R; McAllen, Robin M

2007-08-01

The von Bezold-Jarisch reflex (BJR) is a vagally mediated chemoreflex from the heart and lungs, causing hypopnea, bradycardia, and inhibition of sympathetic vasomotor tone. However, cardiac sympathetic nerve activity (CSNA) has not been systematically compared with vasomotor activity during the BJR. In 11 urethane-anesthetized (1-1.5 g/kg iv), artificially ventilated rats, we measured CSNA simultaneously with lumbar sympathetic activity (LSNA) while the BJR was evoked by right atrial bolus injections of phenylbiguanide (0.5, 1.0, 1.5, and 2 microg). Nerve and heartbeat responses were analyzed by calculating normalized cumulative sums. LSNA and heartbeats were always reduced by the BJR. An excitatory "rebound" component often followed the inhibition of LSNA but never outweighed it. For CSNA, however, excitation usually (in 7 of 11 rats) outweighed any initial inhibition, such that the net response to phenylbiguanide was excitatory. The differences in net response between LSNA, CSNA, and heartbeats were all significant (P < 0.01). A second experimental series on seven rats showed that methyl atropine (1 mg/kg iv) abolished the bradycardia of the BJR, whereas subsequent bilateral vagotomy substantially reduced LSNA and CSNA responses, both excitatory and inhibitory. These findings show that, during the BJR, 1) CSNA is often excited, 2) there may be coactivation of sympathetic and parasympathetic drives to the heart, 3) divergent responses may be evoked simultaneously in cardiac vagal, cardiac sympathetic, and vasomotor nervous pathways, and 4) those divergent responses are mediated primarily by the vagi.

Cardiac Iodine-123-Meta-Iodo-Benzylguanidine Uptake in Carotid Sinus Hypersensitivity.

PubMed

Tan, Maw Pin; Murray, Alan; Hawkins, Terry; Chadwick, Thomas J; Kerr, Simon R J; Parry, Steve W

2015-01-01

Carotid sinus syndrome is the association of carotid sinus hypersensitivity with syncope, unexplained falls and drop attacks in generally older people. We evaluated cardiac sympathetic innervation in this disorder in individuals with carotid sinus syndrome, asymptomatic carotid sinus hypersensitivity and controls without carotid sinus hypersensitivity. Consecutive patients diagnosed with carotid sinus syndrome at a specialist falls and syncope unit were recruited. Asymptomatic carotid sinus hypersensitivity and non-carotid sinus hypersensitivity control participants recruited from a community-dwelling cohort. Cardiac sympathetic innervation was determined using Iodine-123-metaiodobenzylguanidine (123-I-MIBG) scanning. Heart to mediastinal uptake ratio (H:M) were determined for early and late uptake on planar scintigraphy at 20 minutes and 3 hours following intravenous injection of 123-I-MIBG. Forty-two subjects: carotid sinus syndrome (n = 21), asymptomatic carotid sinus hypersensitivity (n = 12) and no carotid sinus hypersensitivity (n = 9) were included. Compared to the non- carotid sinus hypersensitivity control group, the carotid sinus syndrome group had significantly higher early H:M (estimated mean difference, B = 0.40; 95% confidence interval, CI = 0.13 to 0.67, p = 0.005) and late H:M (B = 0.32; 95%CI = 0.03 to 0.62, p = 0.032). There was, however, no significant difference in early H:M (p = 0.326) or late H:M (p = 0.351) between the asymptomatic carotid sinus hypersensitivity group and non- carotid sinus hypersensitivity controls. Cardiac sympathetic neuronal activity is increased relative to age-matched controls in individuals with carotid sinus syndrome but not those with asymptomatic carotid sinus hypersensitivity. Blood pressure and heart rate measurements alone may therefore represent an over simplification in the assessment for carotid sinus syndrome and the relative increase in cardiac sympathetic innervation provides additional clues to understanding the mechanisms behind the symptomatic presentation of carotid sinus hypersensitivity.

Sympathetic network drive during water deprivation does not increase respiratory or cardiac rhythmic sympathetic nerve activity.

PubMed

Holbein, Walter W; Toney, Glenn M

2013-06-15

Effects of water deprivation on rhythmic bursting of sympathetic nerve activity (SNA) were investigated in anesthetized, bilaterally vagotomized, euhydrated (control) and 48-h water-deprived (WD) rats (n = 8/group). Control and WD rats had similar baseline values of mean arterial pressure, heart rate, end-tidal CO2, and central respiratory drive. Although integrated splanchnic SNA (sSNA) was greater in WD rats than controls (P < 0.01), analysis of respiratory rhythmic bursting of sSNA revealed that inspiratory rhythmic burst amplitude was actually smaller (P < 0.005) in WD rats (+68 ± 6%) than controls (+208 ± 20%), and amplitudes of the early expiratory (postinspiratory) trough and late expiratory burst of sSNA were not different between groups. Further analysis revealed that water deprivation had no effect on either the amplitude or periodicity of the cardiac rhythmic oscillation of sSNA. Collectively, these data indicate that the increase of sSNA produced by water deprivation is not attributable to either increased respiratory or cardiac rhythmic burst discharge. Thus the sympathetic network response to acute water deprivation appears to differ from that of chronic sympathoexcitation in neurogenic forms of arterial hypertension, where increased respiratory rhythmic bursting of SNA and baroreflex adaptations have been reported.

LncRNA uc.48+ siRNA improved diabetic sympathetic neuropathy in type 2 diabetic rats mediated by P2X7 receptor in SCG.

PubMed

Wu, Bing; Zhang, Chunping; Zou, Lifang; Ma, Yucheng; Huang, Kangyu; Lv, Qiulan; Zhang, Xi; Wang, Shouyu; Xue, Yun; Yi, Zhihua; Jia, Tianyu; Zhao, Shanhong; Liu, Shuangmei; Xu, Hong; Li, Guilin; Liang, Shangdong

2016-05-01

Diabetic autonomic neuropathy includes the sympathetic ganglionic dysfunction. P2X7 receptor in superior cervical ganglia (SCG) participated in the pathological changes of cardiac dysfunction. Abnormal expression of long noncoding RNAs (lncRNAs) was reported to be involved in nervous system diseases. Our preliminary results obtained from rat lncRNA array profiling revealed that the expression of the uc.48+ was significantly increased in the rat SCG in response to diabetic sympathetic pathology. In this study, we found that lncRNAuc.48+ and P2X7 receptor in the SCG were increased in type 2 diabetic rats and were associated with the cardiac dysfunction. The uc.48+ small interference RNA (siRNA) improved the cardiac autonomic dysfunction and decreased the up-regulation P2X7 and the ratio of phosphorylated extracellular regulated protein kinases1/2 (p-ERK1/2) to ERK1/2 in SCG of type 2 diabetic rats. In conclusion, lncRNA uc.48+ siRNA improved diabetic sympathetic neuropathy in type 2 diabetic rats through regulating the expression of P2X7 and ERK signaling in SCG. Copyright © 2016 Elsevier B.V. All rights reserved.

Aerobic exercise conditioning: a nonpharmacological antiarrhythmic intervention.

PubMed

Billman, George E

2002-02-01

Sudden, unexpected cardiac death due to ventricular fibrillation is the leading cause of death in most industrially developed countries. Yet, despite the enormity of this problem, the development of safe and effective antiarrhythmic therapies has proven to be an elusive goal. In fact, many initially promising antiarrhythmic medications were subsequently found to increase rather than to decrease cardiac mortality. It is now known that cardiac disease alters cardiac autonomic balance and that the patients with the greatest changes in this cardiac neural regulation (i.e., decreased parasympathetic coupled with increased sympathetic activity) are also the patients at the greatest risk for sudden death. A growing body of experimental and epidemiological data demonstrates that aerobic exercise conditioning can dramatically reduce cardiac mortality, even in patients with preexisting cardiac disease. Conversely, the lack of exercise is strongly associated with an increased incidence of many chronic debilitating diseases, including coronary heart disease. Because it is well established that aerobic exercise conditioning can alter autonomic balance (increasing parasympathetic tone and decreasing sympathetic activity), a prudently designed exercise program could prove to be an effective and nonpharmacological way to enhance cardiac electrical stability, thereby protecting against sudden cardiac death.

Mechanisms Regulating the Cardiac Output Response to Cyanide Infusion, a Model of Hypoxia

PubMed Central

Liang, Chang-seng; Huckabee, William E.

1973-01-01

When tissue metabolic changes like those of hypoxia were induced by intra-aortic infusion of cyanide in dogs, cardiac output began to increase after 3 to 5 min, reached a peak (220% of the control value) at 15 min, and returned to control in 40 min. This pattern of cardiac output rise was not altered by vagotomy with or without atropine pretreatment. However, this cardiac output response could be differentiated into three phases by pretreating the animals with agents that block specific activities of the sympatho-adrenal system. First, ganglionic blockade produced by mecamylamine or sympathetic nerve blockade by bretylium abolished the middle phase of the cardiac output seen in the untreated animal, but early and late phases still could be discerned. Second, beta-adrenergic receptor blockade produced by propranolol shortened the total duration of the cardiac output rise by abolishing the late phase. Third, when given together, propranolol and mecamylamine (or bretylium) prevented most of the cardiac output rise that follows the early phase. When cyanide was given to splenectomized dogs, the duration of the cardiac output response was not shortened, but the response became biphasic, resembling that seen after chemical sympathectomy. A similar biphasic response of the cardiac output also resulted from splenic denervation; sham operation or nephrectomy had no effect on the monophasic pattern of the normal response. Splenic venous blood obtained from cyanide-treated dogs, when infused intraportally, caused an increase in cardiac output in recipient dogs; similar infusion of arterial blood had no effects. These results suggest that the cardiac output response to cyanide infusion consists of three components: an early phase, related neither to the autonomic nervous system nor to circulating catecholamines; a middle phase, caused by a nonadrenergic humoral substance released from the spleen by sympathetic stimulation; and a late phase, dependent upon adrenergic receptors but not upon sympathetic transmission. PMID:4750445

Targeted P2X7 R shRNA delivery attenuates sympathetic nerve sprouting and ameliorates cardiac dysfunction in rats with myocardial infarction.

PubMed

Gao, Hongmei; Yin, Jie; Shi, Yugen; Hu, Hesheng; Li, Xiaolu; Xue, Mei; Cheng, Wenjuan; Wang, Ye; Li, Xinran; Li, Yongkang; Wang, Yu; Yan, Suhua

2017-04-01

Inflammation-dominated sympathetic sprouting adjacent to the necrotic region following myocardial infarction (MI) has been implicated in the etiology of arrhythmias resulting in sudden cardiac death; however, the mechanisms responsible remain to be elucidated. Although P2X 7 R is a key immune mediator, its role has yet to be explored. We investigated whether P2X 7 R regulates NF-κB and affects cardiac sympathetic reinnervation in rats undergoing MI. An adenoviral vector with a short hairpin RNA (shRNA) sequence inserted was adopted for the inhibition of P2X 7 R in vivo. Myocardial infarction was induced by left coronary artery ligation, and immediately after that, recombinant P2X 7 R-shRNA adenovirus, negative adenovirus (control), or normal saline solution (vehicle) was injected intramyocardially around the MI region and border areas. A high level of P2X 7 R was activated in the infarcted tissue at an early stage. The administration of P2X 7 R RNAi resulted in the inhibition of Akt and Erk1/2 phosphorylation and decreased the activation of NF-κB and macrophage infiltration, as well as attenuated the expression of nerve growth factor (NGF). Eventually, the NGF-induced sympathetic hyperinnervation was blunted, as assessed by the immunofluorescence of tyrosine hydroxylase (TH) and growth-associated protein 43 (GAP 43). At 7 days post-MI, the arrhythmia score of programmed electrical stimulation in the vehicle-treated infarcted rats was higher than the MI-shRNA group. Further amelioration of cardiac dysfunction was also detected. The administration of P2X 7 R RNAi during the acute inflammatory response phase prevented the process of sympathetic hyperinnervation after MI, which was associated in part with inhibiting the Akt and ERK1/2 pathways and NF-κB activation. © 2016 John Wiley & Sons Ltd.

Neurohumoral indicators of efficacy radiofrequency cardiac denervation

NASA Astrophysics Data System (ADS)

Evtushenko, A. V.; Evtushenko, V. V.; Saushkina, Yu. V.; Lishmanov, Yu. B.; Pokushalov, E. A.; Sergeevichev, D. S.; Gusakova, A. M.; Suslova, T. E.; Dymbrylova, O. N.; Bykov, A. N.; Syryamkin, V. I.; Kistenev, Yu. V.; Anfinogenova, Ya. D.; Smyshlyaev, K. A.; Lotkov, A. I.; Kurlov, I. O.

2015-11-01

In this study, we compared pre- and postoperative parameters of the cardiac sympathetic innervation. The aim of the study was to examine the approaches to evaluating the quality of radiofrequency (RF)-induced cardiac denervation by using non-invasive and laboratory methods. The study included 32 people with long-lasting persistent atrial fibrillation (AF). The patients were divided into 2 groups according to the objectives of the study: group 1 (main) - 21 patients with mitral valve diseases, which simultaneously with radiofrequency ablation (RFA) AF carried out on the effects of the paraganglionic nervous plexuses by C. Pappone (2004) and N. Doll (2008) schemes. The second group (control) contained 11 patients with heart diseases in sinus rhythm (the RF denervation not been performed). All patients, who underwent surgical treatment, were received examination of cardiac sympathetic tone by using 123I-MIBG. All of them made blood analysis from ascending aorta and coronary sinus to determine the level of norepinephrine and its metabolites before and after cardiac denervation. Data of radionuclide examination are correlating with laboratory data.

Effect of Mindfulness Meditation on Perceived Stress Scores and Autonomic Function Tests of Pregnant Indian Women.

PubMed

Muthukrishnan, Shobitha; Jain, Reena; Kohli, Sangeeta; Batra, Swaraj

2016-04-01

Various pregnancy complications like hypertension, preeclampsia have been strongly correlated with maternal stress. One of the connecting links between pregnancy complications and maternal stress is mind-body intervention which can be part of Complementary and Alternative Medicine (CAM). Biologic measures of stress during pregnancy may get reduced by such interventions. To evaluate the effect of Mindfulness meditation on perceived stress scores and autonomic function tests of pregnant Indian women. Pregnant Indian women of 12 weeks gestation were randomised to two treatment groups: Test group with Mindfulness meditation and control group with their usual obstetric care. The effect of Mindfulness meditation on perceived stress scores and cardiac sympathetic functions and parasympathetic functions (Heart rate variation with respiration, lying to standing ratio, standing to lying ratio and respiratory rate) were evaluated on pregnant Indian women. There was a significant decrease in perceived stress scores, a significant decrease of blood pressure response to cold pressor test and a significant increase in heart rate variability in the test group (p< 0.05, significant) which indicates that mindfulness meditation is a powerful modulator of the sympathetic nervous system and can thereby reduce the day-to-day perceived stress in pregnant women. The results of this study suggest that mindfulness meditation improves parasympathetic functions in pregnant women and is a powerful modulator of the sympathetic nervous system during pregnancy.

Diesel Exhaust-Induced Cardiac Dysfunction Is Mediated by Sympathetic Dominance in Heart Failure-Prone Rats

EPA Science Inventory

Short-term exposure to vehicular emissions is associated with adverse cardiac events. Diesel exhaust (DE) may provoke cardiac events through defective co-ordination of the two main autonomic nervous system (ANS) branches. We exposed heart failure-prone rats once to DE (500 g/m3 ...

An Autonomic Link Between Inhaled Diesel Exhaust and Impaired Cardiac Performance: Insight From Treadmill and Doubutamine Challenges in Heart Failure-Prone Rats

EPA Science Inventory

Background: Short-term exposure to vehicular emissions is associated with adverse cardiac events. Diesel exhaust (DE) is an ubiquitous air pollutant believed to provoke cardiac events partly through imbalance of the sympathetic and parasympathetic branches of the autonomic nervo...

Albumin infusion improves renal blood flow autoregulation in patients with acute decompensation of cirrhosis and acute kidney injury.

PubMed

Garcia-Martinez, Rita; Noiret, Lorette; Sen, Sambit; Mookerjee, Rajeshwar; Jalan, Rajiv

2015-02-01

In cirrhotic patients with renal failure, renal blood flow autoregulation curve is shifted to the right, which is consequent upon sympathetic nervous system activation and endothelial dysfunction. Albumin infusion improves renal function in cirrhosis by mechanisms that are incompletely understood. We aimed to determine the effect of albumin infusion on systemic haemodynamics, renal blood flow, renal function and endothelial function in patients with acute decompensation of cirrhosis and acute kidney injury. Twelve patients with refractory ascites and 10 patients with acute decompensation of cirrhosis and acute kidney injury were studied. Both groups were treated with intravenous albumin infusion, 40-60 g/days over 3-4 days. Cardiac and renal haemodynamics were measured. Endothelial activation/dysfunction was assessed using von Willebrand factor and serum nitrite levels. F2α Isoprostanes, resting neutrophil burst and noradrenaline levels were quantified as markers of oxidative stress, endotoxemia and sympathetic activation respectively. Albumin infusion leads to a shift in the renal blood flow autoregulation curve towards normalization, which resulted in a significant increase in renal blood flow. Accordingly, improvement of renal function was observed. In parallel, a significant decrease in sympathetic activation, inflammation/oxidative stress and endothelial activation/dysfunction was documented. Improvement of renal blood flow correlated with improvement in endothelial activation (r = 0.741, P < 0.001). The data suggest that albumin infusion improves renal function in acutely decompensated cirrhotic patients with acute kidney injury by impacting on renal blood flow autoregulation. This is possibly achieved through endothelial stabilization and a reduction in the sympathetic tone, endotoxemia and oxidative stress. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Neurohormonal axis in patients with pulmonary arterial hypertension: friend or foe?

PubMed

de Man, Frances S; Handoko, M Louis; Guignabert, Christophe; Bogaard, Harm J; Vonk-Noordegraaf, Anton

2013-01-01

Despite its description some 25 years ago, neurohormonal activation has long been neglected as an important factor in the pathophysiology of pulmonary arterial hypertension (PAH). Neurohormonal activation was interpreted as a necessary compensatory response to maintain cardiac contractility and systemic blood pressure. Therefore, inhibitors of neurohormonal activity (like β-blockers or angiotensin-converting enzyme inhibitors) are considered contraindicated in current PAH management guidelines. However, recent data revealed that sympathetic overstimulation is strongly related to mortality, and blockade of neurohormonal activity in experimental PAH improved survival and cardiac function. These novel insights shed new light on the role of neurohormonal activity in PAH.

Attenuated sympathetic nerve responses after 24 hours of bed rest

NASA Technical Reports Server (NTRS)

Khan, Mazhar H.; Kunselman, Allen R.; Leuenberger, Urs A.; Davidson, William R Jr; Ray, Chester A.; Gray, Kristen S.; Hogeman, Cynthia S.; Sinoway, Lawrence I.

2002-01-01

Bed rest reduces orthostatic tolerance. Despite decades of study, the cause of this phenomenon remains unclear. In this report we examined hemodynamic and sympathetic nerve responses to graded lower body negative pressure (LBNP) before and after 24 h of bed rest. LBNP allows for baroreceptor disengagement in a graded fashion. We measured heart rate (HR), cardiac output (HR x stroke volume obtained by echo Doppler), and muscle sympathetic nerve activity (MSNA) during a progressive and graded LBNP paradigm. Negative pressure was increased by 10 mmHg every 3 min until presyncope or completion of -60 mmHg. After bed rest, LBNP tolerance was reduced in 11 of 13 subjects (P <.023), HR was greater (P <.002), cardiac output was unchanged, and the ability to augment MSNA at high levels of LBNP was reduced (rate of rise for 30- to 60-mmHg LBNP before bed rest 0.073 bursts x min(-1) x mmHg(-1); after bed rest 0.035 bursts x min(-1) x mmHg(-1); P < 0.016). These findings suggest that 24 h of bed rest reduces sympathetic nerve responses to LBNP.

Recurrent myocardial infarction: Mechanisms of free-floating adaptation and autonomic derangement in networked cardiac neural control.

PubMed

Kember, Guy; Ardell, Jeffrey L; Shivkumar, Kalyanam; Armour, J Andrew

2017-01-01

The cardiac nervous system continuously controls cardiac function whether or not pathology is present. While myocardial infarction typically has a major and catastrophic impact, population studies have shown that longer-term risk for recurrent myocardial infarction and the related potential for sudden cardiac death depends mainly upon standard atherosclerotic variables and autonomic nervous system maladaptations. Investigative neurocardiology has demonstrated that autonomic control of cardiac function includes local circuit neurons for networked control within the peripheral nervous system. The structural and adaptive characteristics of such networked interactions define the dynamics and a new normal for cardiac control that results in the aftermath of recurrent myocardial infarction and/or unstable angina that may or may not precipitate autonomic derangement. These features are explored here via a mathematical model of cardiac regulation. A main observation is that the control environment during pathology is an extrapolation to a setting outside prior experience. Although global bounds guarantee stability, the resulting closed-loop dynamics exhibited while the network adapts during pathology are aptly described as 'free-floating' in order to emphasize their dependence upon details of the network structure. The totality of the results provide a mechanistic reasoning that validates the clinical practice of reducing sympathetic efferent neuronal tone while aggressively targeting autonomic derangement in the treatment of ischemic heart disease.

Cardiovascular dysautonomia in Parkinson disease: from pathophysiology to pathogenesis.

PubMed

Jain, Samay; Goldstein, David S

2012-06-01

Signs or symptoms of impaired autonomic regulation of circulation often attend Parkinson disease (PD). This review covers biomarkers and mechanisms of autonomic cardiovascular abnormalities in PD and related alpha-synucleinopathies. The clearest clinical laboratory correlate of dysautonomia in PD is loss of myocardial noradrenergic innervation, detected by cardiac sympathetic neuroimaging. About 30-40% of PD patients have orthostatic hypotension (OH), defined as a persistent, consistent fall in systolic blood pressure of at least 20 mmHg or diastolic blood pressure of at least 10 mmHg within 3 min of change in position from supine to standing. Neuroimaging evidence of cardiac sympathetic denervation is universal in PD with OH (PD+OH). In PD without OH about half the patients have diffuse left ventricular myocardial sympathetic denervation, a substantial minority have partial denervation confined to the inferolateral or apical walls, and a small number have normal innervation. Among patients with partial denervation the neuronal loss invariably progresses over time, and in those with normal innervation at least some loss eventually becomes evident. Thus, cardiac sympathetic denervation in PD occurs independently of the movement disorder. PD+OH also entails extra-cardiac noradrenergic denervation, but this is not as severe as in pure autonomic failure. PD+OH patients have failure of both the parasympathetic and sympathetic components of the arterial baroreflex. OH in PD therefore seems to reflect a "triple whammy" of cardiac and extra-cardiac noradrenergic denervation and baroreflex failure. In contrast, most patients with multiple system atrophy, which can resemble PD+OH clinically, do not have evidence for cardiac or extra-cardiac noradrenergic denervation. Catecholamines in the neuronal cytoplasm are potentially toxic, via spontaneous and enzyme-catalyzed oxidation. Normally cytoplasmic catecholamines are efficiently taken up into vesicles via the vesicular monoamine transporter. The recent finding of decreased vesicular uptake in Lewy body diseases therefore suggests a pathogenetic mechanism for loss of catecholaminergic neurons in the periphery and brain. Parkinson disease (PD) is one of the most common chronic neurodegenerative diseases of the elderly, and it is likely that as populations age PD will become even more prevalent and more of a public health burden. Severe depletion of dopaminergic neurons of the nigrostriatal system characterizes and likely produces the movement disorder (rest tremor, slowness of movement, rigid muscle tone, and postural instability) in PD. Over the past two decades, compelling evidence has accrued that PD also involves loss of noradrenergic neurons in the heart. This finding supports the view that loss of catecholaminergic neurons, both in the nigrostriatal system and the heart, is fundamental in PD. By the time PD manifests clinically, most of the nigrostriatal dopaminergic neurons are already lost. Identifying laboratory measures-biomarkers-of the disease process is therefore crucial for advances in treatment and prevention. Deposition of the protein, alpha-synuclein, in the form of Lewy bodies in catecholaminergic neurons is a pathologic hallmark of PD. Alpha-synucleinopathy in autonomic neurons may occur early in the pathogenetic process. The timing of cardiac noradrenergic denervation in PD is therefore a key issue. This review updates the field of autonomic cardiovascular abnormalities in PD and related disorders, with emphasis on relationships among striatal dopamine depletion, sympathetic noradrenergic denervation, and alpha-synucleinopathy. Copyright © 2011 Elsevier Inc. All rights reserved.

Lowering of blood pressure by chronic suppression of central sympathetic outflow: insight from prolonged baroreflex activation

PubMed Central

Iliescu, Radu

2012-01-01

Device-based therapy for resistant hypertension by electrical activation of the carotid baroreflex is currently undergoing active clinical investigation, and initial findings from clinical trials have been published. The purpose of this mini-review is to summarize the experimental studies that have provided a conceptual understanding of the mechanisms that account for the long-term lowering of arterial pressure with baroreflex activation. The well established mechanisms mediating the role of the baroreflex in short-term regulation of arterial pressure by rapid changes in peripheral resistance and cardiac function are often extended to long-term pressure control, and the more sluggish actions of the baroreflex on renal excretory function are often not taken into consideration. However, because clinical, experimental, and theoretical evidence indicates that the kidneys play a dominant role in long-term control of arterial pressure, this review focuses on the mechanisms that link baroreflex-mediated reductions in central sympathetic outflow with increases in renal excretory function that lead to sustained reductions in arterial pressure. PMID:22797307

Postural Regulation of Muscle Sympathetic Nerve Activity Before and After Simulated and Actual Microgravity Deconditioning

NASA Technical Reports Server (NTRS)

Pawelczyk, J. A.; Levine, B. D.

1999-01-01

The etiology of orthostatic intolerance after spaceflight is multifaceted. Morphological adaptations, in particular cardiac atrophy, are likely to magnify the decrease in stroke volume that occurs with reductions in cardiac filling pressure when standing. Neural adaptations may be inferred as well, as reductions in carotid-cardiac baroreflex responsiveness have been reported following bedrest deconditioning and spaceflight. Neural control of vascular resistance has not been studied directly when orthostatic intolerance is florid in the hours following spaceflight. However, the increases in systemic vascular resistance and plasma catecholamines during orthostatic stress are inappropriately low in orthostatically intolerant subjects following spaceflight, suggesting that deficits in the regulation of vascular resistance may be associated with hypoadrenergic function. The studies described in this abstract were designed to test this hypothesis.

Pyridostigmine protects against cardiomyopathy associated with adipose tissue browning and improvement of vagal activity in high-fat diet rats.

PubMed

Lu, Yi; Wu, Qing; Liu, Long-Zhu; Yu, Xiao-Jiang; Liu, Jin-Jun; Li, Man-Xiang; Zang, Wei-Jin

2018-04-01

Obesity, a major contributor to the development of cardiovascular diseases, is associated with an autonomic imbalance characterized by sympathetic hyperactivity and diminished vagal activity. Vagal activation plays important roles in weight loss and improvement of cardiac function. Pyridostigmine is a reversible acetylcholinesterase inhibitor, but whether it ameliorates cardiac lipid accumulation and cardiac remodeling in rats fed a high-fat diet has not been determined. This study investigated the effects of pyridostigmine on high-fat diet-induced cardiac dysfunction and explored the potential mechanisms. Rats were fed a normal or high-fat diet and treated with pyridostigmine. Vagal discharge was evaluated using the BL-420S system, and cardiac function by echocardiograms. Lipid deposition and cardiac remodeling were determined histologically. Lipid utility was assessed by qPCR. A high-fat diet led to a significant reduction in vagal discharge and lipid utility and a marked increase in lipid accumulation, cardiac remodeling, and cardiac dysfunction. Pyridostigmine improved vagal activity and lipid metabolism disorder and cardiac remodeling, accompanied by an improvement of cardiac function in high-fat diet-fed rats. An increase in the browning of white adipose tissue in pyridostigmine-treated rats was also observed and linked to the expression of UCP-1 and CIDEA. Additionally, pyridostigmine facilitated activation of brown adipose tissue via activation of the SIRT-1/AMPK/PGC-1α pathway. In conclusion, a high-fat diet resulted in cardiac lipid accumulation, cardiac remodeling, and a significant decrease in vagal discharge. Pyridostigmine ameliorated cardiomyopathy, an effect related to reduced cardiac lipid accumulation, and facilitated the browning of white adipose tissue while activating brown adipose tissue. Copyright © 2018 Elsevier B.V. All rights reserved.

Dynamic analysis of renal nerve activity responses to baroreceptor denervation in hypertensive rats.

PubMed

DiBona, G F; Jones, S Y

2001-04-01

Sinoaortic and cardiac baroreflexes exert important control over renal sympathetic nerve activity. Alterations in these reflex mechanisms contribute to renal sympathoexcitation in hypertension. Nonlinear dynamic analysis was used to examine the chaotic behavior of renal sympathetic nerve activity in normotensive Sprague-Dawley and Wistar-Kyoto rats and spontaneously hypertensive rats before and after complete baroreceptor denervation (sinoaortic and cardiac baroreceptor denervation). The peak interval sequence of synchronized renal sympathetic nerve discharge was extracted and used for analysis. In all rat strains, this yielded systems whose correlation dimensions converged to similar low values over the embedding dimension range of 10 to 15 and whose greatest Lyapunov exponents were positive. In Sprague-Dawley and Wistar-Kyoto rats, compete baroreceptor denervation was associated with decreases in the correlation dimensions (Sprague-DAWLEY: 2.42+/-0.04 to 2.16+/-0.04; Wistar-KYOTO: 2.44+/-0.04 to 2.34+/-0.04) and in the greatest Lyapunov exponents (Sprague-DAWLEY: 0.199+/-0.004 to 0.130+/-0.015; Wistar-KYOTO: 0.196+/-0.002 to 0.136+/-0.010). Spontaneously hypertensive rats had a similar correlation dimension, which was unaffected by complete baroreceptor denervation (2.42+/-0.02 versus 2.42+/-0.03), and a lower value for the greatest Lyapunov exponent, which decreased to a lesser extent after complete baroreceptor denervation (0.183+/-0.006 versus 0.158+/-0.006). These results indicate that removal of sinoaortic and cardiac baroreceptor regulation of renal sympathetic nerve activity is associated with a greater decrease in the chaotic behavior of renal sympathetic nerve activity in normotensive compared with hypertensive rats. This suggests that the central neural mechanisms that regulate renal sympathetic nerve activity in response to alterations in cardiovascular reflex inputs are different in spontaneously hypertensive rats from those in Sprague-Dawley and Wistar-Kyoto rats.

Cardiac Iodine-123-Meta-Iodo-Benzylguanidine Uptake in Carotid Sinus Hypersensitivity

PubMed Central

Tan, Maw Pin; Murray, Alan; Hawkins, Terry; Chadwick, Thomas J.; Kerr, Simon R. J.; Parry, Steve W.

2015-01-01

Background Carotid sinus syndrome is the association of carotid sinus hypersensitivity with syncope, unexplained falls and drop attacks in generally older people. We evaluated cardiac sympathetic innervation in this disorder in individuals with carotid sinus syndrome, asymptomatic carotid sinus hypersensitivity and controls without carotid sinus hypersensitivity. Methods Consecutive patients diagnosed with carotid sinus syndrome at a specialist falls and syncope unit were recruited. Asymptomatic carotid sinus hypersensitivity and non-carotid sinus hypersensitivity control participants recruited from a community-dwelling cohort. Cardiac sympathetic innervation was determined using Iodine-123-metaiodobenzylguanidine (123-I-MIBG) scanning. Heart to mediastinal uptake ratio (H:M) were determined for early and late uptake on planar scintigraphy at 20 minutes and 3 hours following intravenous injection of 123-I-MIBG. Results Forty-two subjects: carotid sinus syndrome (n = 21), asymptomatic carotid sinus hypersensitivity (n = 12) and no carotid sinus hypersensitivity (n = 9) were included. Compared to the non- carotid sinus hypersensitivity control group, the carotid sinus syndrome group had significantly higher early H:M (estimated mean difference, B = 0.40; 95% confidence interval, CI = 0.13 to 0.67, p = 0.005) and late H:M (B = 0.32; 95%CI = 0.03 to 0.62, p = 0.032). There was, however, no significant difference in early H:M (p = 0.326) or late H:M (p = 0.351) between the asymptomatic carotid sinus hypersensitivity group and non- carotid sinus hypersensitivity controls. Conclusions Cardiac sympathetic neuronal activity is increased relative to age-matched controls in individuals with carotid sinus syndrome but not those with asymptomatic carotid sinus hypersensitivity. Blood pressure and heart rate measurements alone may therefore represent an over simplification in the assessment for carotid sinus syndrome and the relative increase in cardiac sympathetic innervation provides additional clues to understanding the mechanisms behind the symptomatic presentation of carotid sinus hypersensitivity. PMID:26057525

Effects of renal denervation on cardiac oxidative stress and local activity of the sympathetic nervous system and renin-angiotensin system in acute myocardial infracted dogs.

PubMed

Feng, Qiaoli; Lu, Chengzhi; Wang, Li; Song, Lijun; Li, Chao; Uppada, Ravi Chandra

2017-02-17

This study sought to evaluate the therapeutic effects of renal denervation (RDN) on acute myocardial infarction (MI) in canines and explore its possible mechanisms of action. Eighteen healthy mongrel dogs were randomly assigned to either the control group, the MI group or the MI + RDN group. To assess cardiac function, left ventricular ejection fraction (LVEF), left ventricular end-diastolic dimension (LVEDD), left ventricular end-systolic dimension (LVESD) and fraction shortening (FS) were recorded. Additionally, haemodynamic parameters such as left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP) and heart rate (HR) were measured. Cardiac oxidative stress levels were evaluated based on the expression of p47 phox mRNA, malondialdehyde (MDA), anti-superoxide anion free radical (ASAFR) and activity of superoxide dismutase (SOD). To measure the local activity of the sympathetic nervous system (SNS) and renin-angiotensin system (RAS), the levels of tyrosine hydroxylase (TH), angiotensin II (AngII), angiotensin-converting enzyme 2 (ACE2), angiotensin (1-7) [Ang(1-7)] and Mas receptor (MasR) in myocardial tissues were recorded. The expression of TH in renal tissue and serum creatinine were used to assess the effectiveness of the RDN procedure and renal function, respectively. We found that MI deteriorated heart function and activated cardiac oxidative stress and the local neurohumoral system, while RDN partially reversed these changes. Compared with the control group, parameters including LVEDD, LVESD, LVEDP and the levels of ASAFR, MDA, p47 phox ,ACE2, Ang(1-7), MasR, AngII and TH-positive nerves were increased (all P < 0.05) in myocardial infracted dogs; meanwhile, LVEF, FS, LVSP and SOD expression were decreased (all P < 0.05). However, after RDN therapy, these changes were significantly improved (P < 0.05), except that there were no significant differences observed in FS or LVSP between the two groups (P = 0.092 and 0.931, respectively). Importantly, the expression of TH, AngII and Ang(1-7) was positively correlated with MDA and negatively correlated with SOD. Between-group comparisons demonstrated no differences in serum creatinine (P = 0.706). RDN attenuated cardiac remodelling and improved heart function by decreasing the level of cardiac oxidative stress and the local activity of the SNS and RAS in cardiac tissues. Additionally, the safety of the RDN procedure was established, as no significant decrease in LVSP or rise in serum creatinine was observed in our study.

The role of the anterodorsal thalami nuclei in the regulation of adrenal medullary function, beta-adrenergic cardiac receptors and anxiety responses in maternally deprived rats under stressful conditions.

PubMed

Suárez, M M; Rivarola, M A; Molina, S M; Levin, G M; Enders, J; Paglini, P

2004-09-01

Maternal separation can interfere with growth and development of the brain and represents a significant risk factor for adult psychopathology. In rodents, prolonged separation from the mother affects the behavioral and endocrine responses to stress for the lifetime of the animal. Limbic structures such as the anterodorsal thalamic nuclei (ADTN) play an important role in the control of neuroendocrine and sympathetic-adrenal function. In view of these findings we hypothesized that the function of the ADTN may be affected in an animal model of maternal deprivation. To test this hypothesis female rats were isolated 4.5 h daily, during the first 3 weeks of life and tested as adults. We evaluated plasma epinephrine (E) and norepinephrine (NE), cardiac adrenoreceptors and anxiety responses after maternal deprivation and variable chronic stress (VCS) in ADTN-lesioned rats. Thirty days after ADTN lesion, in non-maternally deprived rats basal plasma NE concentration was greater and cardiac beta-adrenoreceptor density was lower than that in the sham-lesioned group. Maternal deprivation induced a significant increase in basal plasma NE concentration, which was greater in lesioned rats, and cardiac beta-adrenoreceptor density was decreased in lesioned rats. After VCS plasma catecholamine concentration was much greater in non-maternally deprived rats than in maternally-deprived rats; cardiac beta-adrenoreceptor density was decreased by VCS in both maternally-deprived and non-deprived rats, but more so in non-deprived rats, and further decreased by the ADTN lesion. In the plus maze test, the number of open arm entries was greater in the maternally deprived and in the stressed rats. Thus, sympathetic-adrenal medullary activation produced by VCS was much greater in non-deprived rats, and was linked to a down regulation of myocardial beta-adrenoceptors. The ADTN are not responsible for the reduced catecholamine responses to stress in maternally-deprived rats. Maternal deprivation or chronic stress also induced a long term anxiolytic effect, which was also not affected by ADTN lesion.

Central mechanisms for exercise training-induced reduction in sympatho-excitation in chronic heart failure.

PubMed

Haack, Karla K V; Zucker, Irving H

2015-03-01

The control of sympathetic outflow in the chronic heart failure (CHF) state is markedly abnormal. Patients with heart failure present with increased plasma norepinephrine and increased sympathetic nerve activity. The mechanism for this sympatho-excitation is multiple and varied. Both depression in negative feedback sensory control mechanisms and augmentation of excitatory reflexes contribute to this sympatho-excitation. These include the arterial baroreflex, cardiac reflexes, arterial chemoreflexes and cardiac sympathetic afferent reflexes. In addition, abnormalities in central signaling in autonomic pathways have been implicated in the sympatho-excitatory process in CHF. These mechanisms include increases in central Angiotensin II and the Type 1 receptor, increased in reactive oxygen stress, upregulation in glutamate signaling and NR1 (N-methyl-D-aspartate subtype 1) receptors and others. Exercise training in the CHF state has been shown to reduce sympathetic outflow and result in increased survival and reduced cardiac events. Exercise training has been shown to reduce central Angiotensin II signaling including the Type 1 receptor and reduce oxidative stress by lowering the expression of many of the subunits of NADPH oxidase. In addition, there are profound effects on the central generation of nitric oxide and nitric oxide synthase in sympatho-regulatory areas of the brain. Recent studies have pointed to the balance between Angiotensin Converting Enzyme (ACE) and ACE2, translating into Angiotensin II and Angiotensin 1-7 as important regulators of sympathetic outflow. These enzymes appear to be normalized following exercise training in CHF. Understanding the precise molecular mechanisms by which exercise training is sympatho-inhibitory will uncover new targets for therapy. Copyright © 2014 Elsevier B.V. All rights reserved.

Three Weeks of Overload Training Increases Resting Muscle Sympathetic Activity.

PubMed

Coates, Alexandra M; Incognito, Anthony V; Seed, Jeremy D; Doherty, Connor J; Millar, Philip J; Burr, Jamie F

2018-05-01

Overload training is hypothesized to alter autonomic regulation, although interpretations using indirect measures of heart rate variability are conflicting. The aim of the present study was to examine the effects of overload training on muscle sympathetic nerve activity (MSNA), a direct measure of central sympathetic outflow, in recreational endurance athletes. Measurements of heart rate variability, cardiac baroreflex sensitivity (BRS), MSNA (microneurography), and sympathetic BRS were obtained in 17 healthy triathletes and cyclists after 1 wk of reduced training (baseline) and again after 3 wk of either regular (n = 7) or overload (n = 10) training. After training, the changes (Δ) in peak power output (10 ± 10 vs -12 ± 9 W, P < 0.001), maximal heart rate (-2 ± 4 vs -8 ± 3 bpm, P = 0.006), heart rate variability (SD of normal-to-normal intervals, 27 ± 31 vs -3 ± 25 ms; P = 0.04), and cardiac BRS (7 ± 6 vs -2 ± 8 ms·mm Hg, P = 0.02) differed between the control and overload groups. The change in MSNA burst frequency (-2 ± 2 vs 4 ± 5 bursts per minute, P = 0.02) differed between groups. Across all participants, the changes in resting MSNA and peak power output were correlated negatively (r = -0.51, P = 0.04). No between-group differences in resting heart rate or blood pressure were observed (all P > 0.05). Overload training increased MSNA and attenuated increases in cardiac BRS and heart rate variability observed with regular training. These results support neural adaptations after overload training and suggest that increased central sympathetic outflow may be linked with decreased exercise performance.

Pyridostigmine ameliorates cardiac remodeling induced by myocardial infarction via inhibition of the transforming growth factor-β1/TGF-β1-activated kinase pathway.

PubMed

Lu, Yi; Liu, Jin-Jun; Bi, Xue-Yuan; Yu, Xiao-Jiang; Kong, Shan-Shan; Qin, Fang-Fang; Zhou, Jun; Zang, Wei-Jin

2014-05-01

Autonomic imbalance characterized by sympathetic predominance coinciding with diminished vagal activity is an independent risk factor in cardiovascular diseases. Several studies show that vagus nerve stimulation exerted beneficial effects on cardiac function and survival. In this study, we investigated the vagomimetic effect of pyridostigmine on left ventricular (LV) remodeling in rats after myocardial infarction. After myocardial infarction, surviving rats were treated with or without pyridostigmine (31 mg·kg⁻¹·d⁻¹) for 2 weeks, and hemodynamic parameters were measured. LV tissue was used to assess infarct size and interstitial fibrosis by Masson's trichrome and 0.1% picrosirius red staining. Protein expression of heart tissues was used to assess the efficacy of the treatment. Pyridostigmine markedly reduced myocardial infarct size and improved cardiac diastolic function. These improvements were accompanied with a significant decrease in matrix metalloproteinase-2 expression and collagen deposition. Additionally, pyridostigmine inhibited both transforming growth factor-β1 (TGF-β1) and TGF-β1-activated kinase expression in hearts postmyocardial infarction. Thus, pyridostigmine reduces collagen deposition, attenuates cardiac fibrosis, and improves LV diastolic function after myocardial infarction via TGF-β1/TGF-β1-activated kinase pathway inhibition.

Intrinsic cardiac nervous system in tachycardia induced heart failure.

PubMed

Arora, Rakesh C; Cardinal, Rene; Smith, Frank M; Ardell, Jeffrey L; Dell'Italia, Louis J; Armour, J Andrew

2003-11-01

The purpose of this study was to test the hypothesis that early-stage heart failure differentially affects the intrinsic cardiac nervous system's capacity to regulate cardiac function. After 2 wk of rapid ventricular pacing in nine anesthetized canines, cardiac and right atrial neuronal function were evaluated in situ in response to enhanced cardiac sensory inputs, stimulation of extracardiac autonomic efferent neuronal inputs, and close coronary arterial administration of neurochemicals that included nicotine. Right atrial neuronal intracellular electrophysiological properties were then evaluated in vitro in response to synaptic activation and nicotine. Intrinsic cardiac nicotine-sensitive, neuronally induced cardiac responses were also evaluated in eight sham-operated, unpaced animals. Two weeks of rapid ventricular pacing reduced the cardiac index by 54%. Intrinsic cardiac neurons of paced hearts maintained their cardiac mechano- and chemosensory transduction properties in vivo. They also responded normally to sympathetic and parasympathetic preganglionic efferent neuronal inputs, as well as to locally administered alpha-or beta-adrenergic agonists or angiotensin II. The dose of nicotine needed to modify intrinsic cardiac neurons was 50 times greater in failure compared with normal preparations. That dose failed to alter monitored cardiovascular indexes in failing preparations. Phasic and accommodating neurons identified in vitro displayed altered intracellular membrane properties compared with control, including decreased membrane resistance, indicative of reduced excitability. Early-stage heart failure differentially affects the intrinsic cardiac nervous system's capacity to regulate cardiodynamics. While maintaining its capacity to transduce cardiac mechano- and chemosensory inputs, as well as inputs from extracardiac autonomic efferent neurons, intrinsic cardiac nicotine-sensitive, local-circuit neurons differentially remodel such that their capacity to influence cardiodynamics becomes obtunded.

Exercise improves cardiac autonomic function in obesity and diabetes.

PubMed

Voulgari, Christina; Pagoni, Stamatina; Vinik, Aaron; Poirier, Paul

2013-05-01

Physical activity is a key element in the prevention and management of obesity and diabetes. Regular physical activity efficiently supports diet-induced weight loss, improves glycemic control, and can prevent or delay type 2 diabetes diagnosis. Furthermore, physical activity positively affects lipid profile, blood pressure, reduces the rate of cardiovascular events and associated mortality, and restores the quality of life in type 2 diabetes. However, recent studies have documented that a high percentage of the cardiovascular benefits of exercise cannot be attributed solely to enhanced cardiovascular risk factor modulation. Obesity in concert with diabetes is characterized by sympathetic overactivity and the progressive loss of cardiac parasympathetic influx. These are manifested via different pathogenetic mechanisms, including hyperinsulinemia, visceral obesity, subclinical inflammation and increased thrombosis. Cardiac autonomic neuropathy is an underestimated risk factor for the increased cardiovascular morbidity and mortality associated with obesity and diabetes. The same is true for the role of physical exercise in the restoration of the heart cardioprotective autonomic modulation in these individuals. This review addresses the interplay of cardiac autonomic function in obesity and diabetes, and focuses on the importance of exercise in improving cardiac autonomic dysfunction. Copyright © 2013 Elsevier Inc. All rights reserved.

Limits of clinical tests to screen autonomic function in diabetes type 1.

PubMed

Ducher, M; Bertram, D; Sagnol, I; Cerutti, C; Thivolet, C; Fauvel, J P

2001-11-01

A precocious detection of cardiac autonomic dysfunction is of major clinical interest that could lead to a more intensive supervision of diabetic patients. However, classical clinical exploration of cardiac autonomic function is not easy to undertake in a reproducible way. Thus, respective interests of autonomic nervous parameters provided by both clinical tests and computerized analysis of resting blood pressure were checked in type 1 diabetic patients without orthostatic hypotension and microalbuminuria. Thirteen diabetic subjects matched for age and gender to thirteen healthy subjects volunteered to participate to the study. From clinical tests (standing up, deep breathing, Valsalva maneuver, handgrip test), autonomic function was scored according to Ewing's methodology. Analysis of resting beat to beat blood pressure provided autonomic indices of the cardiac function (spectral analysis or Z analysis). 5 of the 13 diabetic patients exhibited a pathological score (more than one pathological response) suggesting the presence of cardiovascular autonomic dysfunction. The most discriminative test was the deep breathing test. However, spectral indices of BP recordings and baro-reflex sensitivity (BRS) of these 5 subjects were similar to those of healthy subjects and of remaining diabetic subjects. Alteration in Ewing's score given by clinical tests may not reflect an alteration of cardiac autonomic function in asymptomatic type 1 diabetic patients, because spectral indices of sympathetic and parasympathetic (including BRS) function were within normal range. Our results strongly suggest to confront results provided by both methodologies before concluding to an autonomic cardiac impairment in asymptomatic diabetic patients.

Reflex effects on components of synchronized renal sympathetic nerve activity.

PubMed

DiBona, G F; Jones, S Y

1998-09-01

The effects of peripheral thermal receptor stimulation (tail in hot water, n = 8, anesthetized) and cardiac baroreceptor stimulation (volume loading, n = 8, conscious) on components of synchronized renal sympathetic nerve activity (RSNA) were examined in rats. The peak height and peak frequency of synchronized RSNA were determined. The renal sympathoexcitatory response to peripheral thermal receptor stimulation was associated with an increase in the peak height. The renal sympathoinhibitory response to cardiac baroreceptor stimulation was associated with a decrease in the peak height. Although heart rate was significantly increased with peripheral thermal receptor stimulation and significantly decreased with cardiac baroreceptor stimulation, peak frequency was unchanged. As peak height reflects the number of active fibers, reflex increases and decreases in synchronized RSNA are mediated by parallel increases and decreases in the number of active renal nerve fibers rather than changes in the centrally based rhythm or peak frequency. The increase in the number of active renal nerve fibers produced by peripheral thermal receptor stimulation reflects the engagement of a unique group of silent renal sympathetic nerve fibers with a characteristic response pattern to stimulation of arterial baroreceptors, peripheral and central chemoreceptors, and peripheral thermal receptors.

Adrenergic Blockade Bi-directionally and Asymmetrically Alters Functional Brain-Heart Communication and Prolongs Electrical Activities of the Brain and Heart during Asphyxic Cardiac Arrest

PubMed Central

Tian, Fangyun; Liu, Tiecheng; Xu, Gang; Li, Duan; Ghazi, Talha; Shick, Trevor; Sajjad, Azeem; Wang, Michael M.; Farrehi, Peter; Borjigin, Jimo

2018-01-01

Sudden cardiac arrest is a leading cause of death in the United States. The neurophysiological mechanism underlying sudden death is not well understood. Previously we have shown that the brain is highly stimulated in dying animals and that asphyxia-induced death could be delayed by blocking the intact brain-heart neuronal connection. These studies suggest that the autonomic nervous system plays an important role in mediating sudden cardiac arrest. In this study, we tested the effectiveness of phentolamine and atenolol, individually or combined, in prolonging functionality of the vital organs in CO2-mediated asphyxic cardiac arrest model. Rats received either saline, phentolamine, atenolol, or phentolamine plus atenolol, 30 min before the onset of asphyxia. Electrocardiogram (ECG) and electroencephalogram (EEG) signals were simultaneously collected from each rat during the entire process and investigated for cardiac and brain functions using a battery of analytic tools. We found that adrenergic blockade significantly suppressed the initial decline of cardiac output, prolonged electrical activities of both brain and heart, asymmetrically altered functional connectivity within the brain, and altered, bi-directionally and asymmetrically, functional, and effective connectivity between the brain and heart. The protective effects of adrenergic blockers paralleled the suppression of brain and heart connectivity, especially in the right hemisphere associated with central regulation of sympathetic function. Collectively, our results demonstrate that blockade of brain-heart connection via alpha- and beta-adrenergic blockers significantly prolonged the detectable activities of both the heart and the brain in asphyxic rat. The beneficial effects of combined alpha and beta blockers may help extend the survival of cardiac arrest patients. PMID:29487541

Adrenergic Blockade Bi-directionally and Asymmetrically Alters Functional Brain-Heart Communication and Prolongs Electrical Activities of the Brain and Heart during Asphyxic Cardiac Arrest.

PubMed

Tian, Fangyun; Liu, Tiecheng; Xu, Gang; Li, Duan; Ghazi, Talha; Shick, Trevor; Sajjad, Azeem; Wang, Michael M; Farrehi, Peter; Borjigin, Jimo

2018-01-01

Sudden cardiac arrest is a leading cause of death in the United States. The neurophysiological mechanism underlying sudden death is not well understood. Previously we have shown that the brain is highly stimulated in dying animals and that asphyxia-induced death could be delayed by blocking the intact brain-heart neuronal connection. These studies suggest that the autonomic nervous system plays an important role in mediating sudden cardiac arrest. In this study, we tested the effectiveness of phentolamine and atenolol, individually or combined, in prolonging functionality of the vital organs in CO 2 -mediated asphyxic cardiac arrest model. Rats received either saline, phentolamine, atenolol, or phentolamine plus atenolol, 30 min before the onset of asphyxia. Electrocardiogram (ECG) and electroencephalogram (EEG) signals were simultaneously collected from each rat during the entire process and investigated for cardiac and brain functions using a battery of analytic tools. We found that adrenergic blockade significantly suppressed the initial decline of cardiac output, prolonged electrical activities of both brain and heart, asymmetrically altered functional connectivity within the brain, and altered, bi-directionally and asymmetrically, functional, and effective connectivity between the brain and heart. The protective effects of adrenergic blockers paralleled the suppression of brain and heart connectivity, especially in the right hemisphere associated with central regulation of sympathetic function. Collectively, our results demonstrate that blockade of brain-heart connection via alpha- and beta-adrenergic blockers significantly prolonged the detectable activities of both the heart and the brain in asphyxic rat. The beneficial effects of combined alpha and beta blockers may help extend the survival of cardiac arrest patients.

Synaptic Plasticity in Cardiac Innervation and Its Potential Role in Atrial Fibrillation

PubMed Central

Ashton, Jesse L.; Burton, Rebecca A. B.; Bub, Gil; Smaill, Bruce H.; Montgomery, Johanna M.

2018-01-01

Synaptic plasticity is defined as the ability of synapses to change their strength of transmission. Plasticity of synaptic connections in the brain is a major focus of neuroscience research, as it is the primary mechanism underpinning learning and memory. Beyond the brain however, plasticity in peripheral neurons is less well understood, particularly in the neurons innervating the heart. The atria receive rich innervation from the autonomic branch of the peripheral nervous system. Sympathetic neurons are clustered in stellate and cervical ganglia alongside the spinal cord and extend fibers to the heart directly innervating the myocardium. These neurons are major drivers of hyperactive sympathetic activity observed in heart disease, ventricular arrhythmias, and sudden cardiac death. Both pre- and postsynaptic changes have been observed to occur at synapses formed by sympathetic ganglion neurons, suggesting that plasticity at sympathetic neuro-cardiac synapses is a major contributor to arrhythmias. Less is known about the plasticity in parasympathetic neurons located in clusters on the heart surface. These neuronal clusters, termed ganglionated plexi, or “little brains,” can independently modulate neural control of the heart and stimulation that enhances their excitability can induce arrhythmia such as atrial fibrillation. The ability of these neurons to alter parasympathetic activity suggests that plasticity may indeed occur at the synapses formed on and by ganglionated plexi neurons. Such changes may not only fine-tune autonomic innervation of the heart, but could also be a source of maladaptive plasticity during atrial fibrillation. PMID:29615932

Neurohumoral indicators of efficacy radiofrequency cardiac denervation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Evtushenko, A. V., E-mail: ave@cardio-tomsk.ru; Evtushenko, V. V.; Federal State Budgetary Scientific Institution “Research Institute for Cardiology”, Tomsk

In this study, we compared pre- and postoperative parameters of the cardiac sympathetic innervation. The aim of the study was to examine the approaches to evaluating the quality of radiofrequency (RF)-induced cardiac denervation by using non-invasive and laboratory methods. The study included 32 people with long-lasting persistent atrial fibrillation (AF). The patients were divided into 2 groups according to the objectives of the study: group 1 (main) - 21 patients with mitral valve diseases, which simultaneously with radiofrequency ablation (RFA) AF carried out on the effects of the paraganglionic nervous plexuses by C. Pappone (2004) and N. Doll (2008) schemes.more » The second group (control) contained 11 patients with heart diseases in sinus rhythm (the RF denervation not been performed). All patients, who underwent surgical treatment, were received examination of cardiac sympathetic tone by using {sup 123}I-MIBG. All of them made blood analysis from ascending aorta and coronary sinus to determine the level of norepinephrine and its metabolites before and after cardiac denervation. Data of radionuclide examination are correlating with laboratory data.« less

Polyphenols, Antioxidants and the Sympathetic Nervous System.

PubMed

Bruno, Rosa Maria; Ghiadoni, Lorenzo

2018-01-01

A high dietary intake of polyphenols has been associated with a reduced cardiovascular mortality, due to their antioxidant properties. However, growing evidence suggests that counteracting oxidative stress in cardiovascular disease might also reduce sympathetic nervous system overactivity. This article reviews the most commonly used techniques to measure sympathetic activity in humans; the role of sympathetic activation in the pathophysiology of cardiovascular diseases; current evidence demonstrating that oxidative stress is involved in the regulation of sympathetic activity and how antioxidants and polyphenols might counteract sympathetic overactivity, particularly focusing on preliminary data from human studies. The main mechanisms by which polyphenols are cardioprotective are related to the improvement of vascular function and their anti-atherogenic effect. Furthermore, a blood pressure-lowering effect was consistently demonstrated in randomized controlled trials in humans, when the effect of flavonoid-rich foods, such as tea and chocolate, was tested. More recent studies suggest that inhibition of sympathetic overactivity might be one of the mechanisms by which these substances exert their cardioprotective effects. Indeed, an increased adrenergic traffic to the vasculature is a major mechanism of disease in a number of cardiovascular and extra-cardiac diseases, including hypertension, obesity, metabolic syndrome and heart failure. A considerable body of evidence, mostly from experimental studies, support the hypothesis that reactive oxygen species might exert sympathoexcitatory effects both at the central and at the peripheral level. Accordingly, supplementation with antioxidants might reduce adrenergic overdrive to the vasculature and blunt cardiovascular reactivity to stress. While supplementation with "classical" antioxidants such as ROS-scavengers has many limitations, increasing the intake of polyphenol-rich foods seems to be a promising novel therapeutic strategy to reduce the deleterious effects of increased adrenergic tone, particularly in essential hypertension. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Spaceflight alters autonomic regulation of arterial pressure in humans

NASA Technical Reports Server (NTRS)

Fritsch-Yelle, Janice M.; Charles, John B.; Jones, Michele M.; Beightol, Larry A.; Eckberg, Dwain L.

1994-01-01

Spaceflight is associated with decreased orthostatic tolerance after landing. Short-duration spaceflight (4 - 5 days) impairs one neutral mechanism: the carotid baroreceptor-cardiac reflex. To understand the effects of longer-duration spaceflight on baroreflex function, we measured R-R interval power spectra, antecubital vein plasma catecholamine levels, carotid baroreceptor-cardiac reflex responses, responses to Valsalva maneuvers, and orthostatic tolerance in 16 astronauts before and after shuttle missions lasting 8 - 14 days. We found the following changes between preflight and landing day: (1) orthostatic tolerance decreased; (2) R-R interval spectral power in the 0.05- to 0.15-Hz band increased; (3) plasma norepinephrine and epinephrine levels increased; (4) the slope, range, and operational point of the carotid baroreceptor cardiac reflex response decreased; and (5) blood pressure and heart rate responses to Valsalva maneuvers were altered. Autonomic changes persisted for several days after landing. These results provide further evidence of functionally relevent reductions in parasympathetic and increases in sympathetic influences on arterial pressure control after spaceflight.

Effects of a hydrotherapy programme on symbolic and complexity dynamics of heart rate variability and aerobic capacity in fibromyalgia patients.

PubMed

Zamunér, Antonio Roberto; Andrade, Carolina P; Forti, Meire; Marchi, Andrea; Milan, Juliana; Avila, Mariana Arias; Catai, Aparecida Maria; Porta, Alberto; Silva, Ester

2015-01-01

To evaluate the effects of a hydrotherapy programme on aerobic capacity and linear and non-linear dynamics of heart rate variability (HRV) in women with fibromyalgia syndrome (FMS). 20 women with FMS and 20 healthy controls (HC) took part in the study. The FMS group was evaluated at baseline and after a 16-week hydrotherapy programme. All participants underwent cardiopulmonary exercise testing on a cycle ergometer and RR intervals recording in supine and standing positions. The HRV was analysed by linear and non-linear methods. The current level of pain, the tender points, the pressure pain threshold and the impact of FMS on quality of life were assessed. The FMS patients presented higher cardiac sympathetic modulation, lower vagal modulation and lower complexity of HRV in supine position than the HC. Only the HC decreased the complexity indices of HRV during orthostatic stimulus. After a 16-week hydrotherapy programme, the FMS patients increased aerobic capacity, decreased cardiac sympathetic modulation and increased vagal modulation and complexity dynamics of HRV in supine. The FMS patients also improved their cardiac autonomic adjustments to the orthostatic stimulus. Associations between improvements in non-linear dynamics of HRV and improvements in pain and in the impact of FMS on quality of life were found. A 16-week hydrotherapy programme proved to be effective in ameliorating symptoms, aerobic functional capacity and cardiac autonomic control in FMS patients. Improvements in the non-linear dynamics of HRV were related to improvements in pain and in the impact of FMS on quality of life.

Influence of simulated microgravity on the sympathetic response to exercise

NASA Technical Reports Server (NTRS)

Woodman, C. R.; Kregel, K. C.; Tipton, C. M.

1997-01-01

Rats exposed to simulated conditions of microgravity exhibit reductions in aerobic exercise capacity that may be due to an impaired ability of the sympathetic nervous system (SNS) to mediate an increase in cardiac output and to redistribute blood flow. The purpose of this study was to quantify the sympathetic response to exercise in rats after exposure to 14 days of simulated microgravity or control conditions. To achieve this aim, rats were exposed to 14 days of head-down suspension (HDS) or cage control (CC) conditions. On day 14, norepinephrine (NE) synthesis was blocked with alpha-methyl-p-tyrosine, and the rate of NE depletion after synthesis blockade was used to estimate SNS activity in the left ventricle, spleen, and soleus muscle during treadmill exercise at 75% of maximal oxygen uptake. When compared with CC rats, the sympathetic response to exercise in HDS rats was characterized by a lower rate of NE depletion in the left ventricle (-82%) and spleen (-42%). The rate of NE depletion in the soleus muscle was 47% higher. These differences could contribute to the decrement in aerobic capacity of HDS rats by impairing their ability to augment cardiac output and to redirect blood flow to actively contracting skeletal muscle during exercise.

Sympathetic vasoconstriction and orthostatic intolerance after simulated microgravity.

PubMed

Kamiya, A; Michikami, D; Fu, Q; Iwase, S; Mano, T

1999-07-01

Upon a return to the earth from spaceflight, astronauts often become presyncope during standing. This orthostatic intolerance is provoked by the exposure to the stimulation model of microgravitational environment in humans, 6 degrees head-down bed rest (HDBR). The mechanism for the orthostatic hypotension after microgravity remains unclear. It has been reported that a microgravity-induced loss of circulatory blood volume, a withdrawal of vagal tone, or a reduction of carotid-cardiac baroreflex function may relate to this phenomenon. A recent article has reported that astronauts who showed presyncopal events after spaceflight had subnormal increases in plasma norepinephrine under the standing tests, suggesting that a hypoadrenergic responsiveness to orthostatic stress may partly contribute to postflight orthostatic hypotension. However, it is unclear how and whether or not the sympathetic outflow to peripheral vessels and the release of norepinephrine from sympathetic nerve terminals were altered after microgravity. The vasomotor sympathetic outflow to the skeletal muscle can be directly recorded as muscle sympathetic nerve activity (MSNA) using a microneurographic technique. In addition, the rate of an increase in plasma norepinephrine per that in MSNA in response to applied orthostatic stress can partly indicate the norepinephrine release to sympathetic stimuli as a trial assessment. Therefore, we performed 60 degrees head-up tilt (HUT) tests before and after 14 days of HDBR, and examined the differences in the MSNA response and the indicated norepinephrine release during HUT tests between the subjects who did (defined as the fainters) and those who did not (defined as the nonfainters) become presyncopal in HUT tests after HDBR.

Systemic and Renal-Specific Sympathoinhibition in Obesity Hypertension

PubMed Central

Lohmeier, Thomas E.; Iliescu, Radu; Liu, Boshen; Henegar, Jeffrey R.; Maric-Bilkan, Christine; Irwin, Eric D.

2012-01-01

Chronic pressure-mediated baroreflex activation suppresses renal sympathetic nerve activity. Recent observations indicate that chronic electrical activation of the carotid baroreflex produces sustained reductions in global sympathetic activity and arterial pressure. Thus, we investigated the effects of global and renal specific suppression of sympathetic activity in dogs with sympathetically-mediated, obesity-induced hypertension by comparing the cardiovascular, renal, and neurohormonal responses to chronic baroreflex activation and bilateral surgical renal denervation. After control measurements, the diet was supplemented with beef fat while sodium intake was held constant. After 4 weeks on the high-fat, when body weight had increased ~a 50%, fat intake was reduced to a level that maintained this body weight. This weight increase was associated with an increase in mean arterial pressure from 100±2 to 117±3 mm Hg and heart rate from 86±3 to 130±4 bpm. The hypertension was associated with a marked increase in cumulative sodium balance despite ~ a 35% increase in GFR. The importance of increased tubular reabsorption to sodium retention was further reflected by ~ a 35% decrease in fractional sodium excretion. Subsequently, both chronic baroreflex activation (7 days) and renal denervation decreased plasma renin activity and abolished the hypertension. However, baroreflex activation also suppressed systemic sympathetic activity and tachycardia and reduced glomerular hyperfiltration while increasing fractional sodium excretion. In contrast, GFR increased further after renal denervation. Thus, by improving autonomic control of cardiac function and diminishing glomerular hyperfiltration, suppression of global sympathetic activity by baroreflex activation may have beneficial effects in obesity beyond simply attenuating hypertension. PMID:22184321

Cardiac Impairment Evaluated by Transesophageal Echocardiography and Invasive Measurements in Rats Undergoing Sinoaortic Denervation

PubMed Central

Sirvente, Raquel A.; Irigoyen, Maria C.; Souza, Leandro E.; Mostarda, Cristiano; La Fuente, Raquel N.; Candido, Georgia O.; Souza, Pamella R. M.; Medeiros, Alessandra; Mady, Charles; Salemi, Vera M. C.

2014-01-01

Background Sympathetic hyperactivity may be related to left ventricular (LV) dysfunction and baro- and chemoreflex impairment in hypertension. However, cardiac function, regarding the association of hypertension and baroreflex dysfunction, has not been previously evaluated by transesophageal echocardiography (TEE) using intracardiac echocardiographic catheter. Methods and Results We evaluated exercise tests, baroreflex sensitivity and cardiovascular autonomic control, cardiac function, and biventricular invasive pressures in rats 10 weeks after sinoaortic denervation (SAD). The rats (n = 32) were divided into 4 groups: 16 Wistar (W) with (n = 8) or without SAD (n = 8) and 16 spontaneously hypertensive rats (SHR) with (n = 8) or without SAD (SHRSAD) (n = 8). Blood pressure (BP) and heart rate (HR) did not change between the groups with or without SAD; however, compared to W, SHR groups had higher BP levels and BP variability was increased. Exercise testing showed that SHR had better functional capacity compared to SAD and SHRSAD. Echocardiography showed left ventricular (LV) concentric hypertrophy; segmental systolic and diastolic biventricular dysfunction; indirect signals of pulmonary arterial hypertension, mostly evident in SHRSAD. The end-diastolic right ventricular (RV) pressure increased in all groups compared to W, and the end-diastolic LV pressure increased in SHR and SHRSAD groups compared to W, and in SHRSAD compared to SAD. Conclusions Our results suggest that baroreflex dysfunction impairs cardiac function, and increases pulmonary artery pressure, supporting a role for baroreflex dysfunction in the pathogenesis of hypertensive cardiac disease. Moreover, TEE is a useful and feasible noninvasive technique that allows the assessment of cardiac function, particularly RV indices in this model of cardiac disease. PMID:24828834

Defunct brain stem cardiovascular regulation underlies cardiovascular collapse associated with methamphetamine intoxication.

PubMed

Li, Faith C H; Yen, J C; Chan, Samuel H H; Chang, Alice Y W

2012-02-07

Intoxication from the psychostimulant methamphetamine (METH) because of cardiovascular collapse is a common cause of death within the abuse population. For obvious reasons, the heart has been taken as the primary target for this METH-induced toxicity. The demonstration that failure of brain stem cardiovascular regulation, rather than the heart, holds the key to cardiovascular collapse induced by the pesticide mevinphos implicates another potential underlying mechanism. The present study evaluated the hypothesis that METH effects acute cardiovascular depression by dampening the functional integrity of baroreflex via an action on brain stem nuclei that are associated with this homeostatic mechanism. The distribution of METH in brain and heart on intravenous administration in male Sprague-Dawley rats, and the resultant changes in arterial pressure (AP), heart rate (HR) and indices for baroreflex-mediated sympathetic vasomotor tone and cardiac responses were evaluated, alongside survival rate and time. Intravenous administration of METH (12 or 24 mg/kg) resulted in a time-dependent and dose-dependent distribution of the psychostimulant in brain and heart. The distribution of METH to neural substrates associated with brain stem cardiovascular regulation was significantly larger than brain targets for its neurological and psychological effects; the concentration of METH in cardiac tissues was the lowest among all tissues studied. In animals that succumbed to METH, the baroreflex-mediated sympathetic vasomotor tone and cardiac response were defunct, concomitant with cessation of AP and HR. On the other hand, although depressed, those two indices in animals that survived were maintained, alongside sustainable AP and HR. Linear regression analysis further revealed that the degree of dampening of brain stem cardiovascular regulation was positively and significantly correlated with the concentration of METH in key neural substrate involved in this homeostatic mechanism. We conclude that on intravenous administration, METH exhibits a preferential distribution to brain stem nuclei that are associated with cardiovascular regulation. We further found that the concentration of METH in those brain stem sites dictates the extent that baroreflex-mediated sympathetic vasomotor tone and cardiac responses are compromised, which in turn determines survival or fatality because of cardiovascular collapse.

Defunct brain stem cardiovascular regulation underlies cardiovascular collapse associated with methamphetamine intoxication

PubMed Central

2012-01-01

Background Intoxication from the psychostimulant methamphetamine (METH) because of cardiovascular collapse is a common cause of death within the abuse population. For obvious reasons, the heart has been taken as the primary target for this METH-induced toxicity. The demonstration that failure of brain stem cardiovascular regulation, rather than the heart, holds the key to cardiovascular collapse induced by the pesticide mevinphos implicates another potential underlying mechanism. The present study evaluated the hypothesis that METH effects acute cardiovascular depression by dampening the functional integrity of baroreflex via an action on brain stem nuclei that are associated with this homeostatic mechanism. Methods The distribution of METH in brain and heart on intravenous administration in male Sprague-Dawley rats, and the resultant changes in arterial pressure (AP), heart rate (HR) and indices for baroreflex-mediated sympathetic vasomotor tone and cardiac responses were evaluated, alongside survival rate and time. Results Intravenous administration of METH (12 or 24 mg/kg) resulted in a time-dependent and dose-dependent distribution of the psychostimulant in brain and heart. The distribution of METH to neural substrates associated with brain stem cardiovascular regulation was significantly larger than brain targets for its neurological and psychological effects; the concentration of METH in cardiac tissues was the lowest among all tissues studied. In animals that succumbed to METH, the baroreflex-mediated sympathetic vasomotor tone and cardiac response were defunct, concomitant with cessation of AP and HR. On the other hand, although depressed, those two indices in animals that survived were maintained, alongside sustainable AP and HR. Linear regression analysis further revealed that the degree of dampening of brain stem cardiovascular regulation was positively and significantly correlated with the concentration of METH in key neural substrate involved in this homeostatic mechanism. Conclusions We conclude that on intravenous administration, METH exhibits a preferential distribution to brain stem nuclei that are associated with cardiovascular regulation. We further found that the concentration of METH in those brain stem sites dictates the extent that baroreflex-mediated sympathetic vasomotor tone and cardiac responses are compromised, which in turn determines survival or fatality because of cardiovascular collapse. PMID:22313577

Recurrent myocardial infarction: Mechanisms of free-floating adaptation and autonomic derangement in networked cardiac neural control

PubMed Central

Ardell, Jeffrey L.; Shivkumar, Kalyanam; Armour, J. Andrew

2017-01-01

The cardiac nervous system continuously controls cardiac function whether or not pathology is present. While myocardial infarction typically has a major and catastrophic impact, population studies have shown that longer-term risk for recurrent myocardial infarction and the related potential for sudden cardiac death depends mainly upon standard atherosclerotic variables and autonomic nervous system maladaptations. Investigative neurocardiology has demonstrated that autonomic control of cardiac function includes local circuit neurons for networked control within the peripheral nervous system. The structural and adaptive characteristics of such networked interactions define the dynamics and a new normal for cardiac control that results in the aftermath of recurrent myocardial infarction and/or unstable angina that may or may not precipitate autonomic derangement. These features are explored here via a mathematical model of cardiac regulation. A main observation is that the control environment during pathology is an extrapolation to a setting outside prior experience. Although global bounds guarantee stability, the resulting closed-loop dynamics exhibited while the network adapts during pathology are aptly described as ‘free-floating’ in order to emphasize their dependence upon details of the network structure. The totality of the results provide a mechanistic reasoning that validates the clinical practice of reducing sympathetic efferent neuronal tone while aggressively targeting autonomic derangement in the treatment of ischemic heart disease. PMID:28692680

Effort Deficits and Depression: The Influence of Anhedonic Depressive Symptoms on Cardiac Autonomic Activity During a Mental Challenge

PubMed Central

Silvia, Paul J.; Nusbaum, Emily C.; Eddington, Kari M.; Beaty, Roger E.; Kwapil, Thomas R.

2014-01-01

Motivational approaches to depression emphasize the role of dysfunctional motivational dynamics, particularly diminished reward and incentive processes associated with anhedonia. A study examined how anhedonic depressive symptoms, measured continuously across a wide range of severity, influenced the physiological mobilization of effort during a cognitive task. Using motivational intensity theory as a guide, we expected that the diminished incentive value associated with anhedonic depressive symptoms would reduce effort during a “do your best” challenge (also known as an unfixed or self-paced challenge), in which effort is a function of the value of achieving the task’s goal. Using impedance cardiography, two cardiac autonomic responses were assessed: pre-ejection period (PEP), a measure of sympathetic activity and our primary measure of interest, and respiratory sinus arrhythmia (RSA), a measure of parasympathetic activity. As expected, PEP slowed from baseline to task as anhedonic depressive symptoms increased (as measured with the DASS Depression scale), indicating diminished effort-related sympathetic activity. No significant effects appeared for RSA. The findings support motivational intensity theory as a translational model of effort processes in depression and clarify some inconsistent effects of depressive symptoms on effort-related physiology found in past work. PMID:25431505

Breast feeding, bottle feeding, and maternal autonomic responses to stress.

PubMed

Mezzacappa, Elizabeth Sibolboro; Kelsey, Robert M; Katkin, Edward S

2005-04-01

The aim of this study was to examine the effects of breast feeding on autonomic nervous system (ANS) response to stressors. Sympathetic and parasympathetic activities were examined before, during, and after standard laboratory stressors in women who were either exclusively breast feeding (n=14) or nonexclusively breast feeding (n=14), and in non-postpartum controls (n=15). Mothers who breast fed exclusively showed greater levels of parasympathetic cardiac modulation and slower heart rate (HR) throughout the session and less HR increase and preejection period (PEP) shortening to mental arithmetic (MA) than did nonexclusive breast feeders and controls. Nonexclusive breast-feeders showed greater electrodermal reactivity to, and greater differences in skin conductance response (SCR) frequency between baseline and recovery from cold pressor (CP) than did either exclusive breast-feeders or controls. Sympathetic activity was negatively related to the number of breast feedings and positively related to bottle feedings. Breast feeding shifts maternal ANS balance toward relatively greater parasympathetic and lesser sympathetic activity; the opposite occurs with bottle feeding. The frequency of feeding also is a critical factor in determining breast feeding effects on maternal ANS function.

Vagal Nerve Stimulation Therapy: What Is Being Stimulated?

PubMed Central

Kember, Guy; Ardell, Jeffrey L.; Armour, John A.; Zamir, Mair

2014-01-01

Vagal nerve stimulation in cardiac therapy involves delivering electrical current to the vagal sympathetic complex in patients experiencing heart failure. The therapy has shown promise but the mechanisms by which any benefit accrues is not understood. In this paper we model the response to increased levels of stimulation of individual components of the vagal sympathetic complex as a differential activation of each component in the control of heart rate. The model provides insight beyond what is available in the animal experiment in as much as allowing the simultaneous assessment of neuronal activity throughout the cardiac neural axis. The results indicate that there is sensitivity of the neural network to low level subthreshold stimulation. This leads us to propose that the chronic effects of vagal nerve stimulation therapy lie within the indirect pathways that target intrinsic cardiac local circuit neurons because they have the capacity for plasticity. PMID:25479368

Vagal nerve stimulation therapy: what is being stimulated?

PubMed

Kember, Guy; Ardell, Jeffrey L; Armour, John A; Zamir, Mair

2014-01-01

Vagal nerve stimulation in cardiac therapy involves delivering electrical current to the vagal sympathetic complex in patients experiencing heart failure. The therapy has shown promise but the mechanisms by which any benefit accrues is not understood. In this paper we model the response to increased levels of stimulation of individual components of the vagal sympathetic complex as a differential activation of each component in the control of heart rate. The model provides insight beyond what is available in the animal experiment in as much as allowing the simultaneous assessment of neuronal activity throughout the cardiac neural axis. The results indicate that there is sensitivity of the neural network to low level subthreshold stimulation. This leads us to propose that the chronic effects of vagal nerve stimulation therapy lie within the indirect pathways that target intrinsic cardiac local circuit neurons because they have the capacity for plasticity.

Treadmill stress test after diesel exhaust particulate exposure reveals a time-dependent shift from parasympathetic to sympathetic dominance

EPA Science Inventory

Epidemiological studies suggest that particulate matter (PM) air pollution is a major trigger of acute cardiac events-including arrhythmia-especially in those with preexisting cardiac disease. Diesel exhaust (DE) contributes the majority of urban fine and ultrafine PM, and is thu...

Exploring relationships for visceral and somatic pain with autonomic control and personality.

PubMed

Paine, Peter; Kishor, Jessin; Worthen, Sian F; Gregory, Lloyd J; Aziz, Qasim

2009-08-01

The autonomic nervous system (ANS) integrates afferent and motor activity for homeostatic processes including pain. The aim of the study was to compare hitherto poorly characterised relations between brainstem autonomic control and personality in response to visceral and somatic pain. Eighteen healthy subjects (16 females, mean age 34) had recordings during rest and pain of heart rate (HR), cardiac vagal tone (CVT), cardiac sensitivity to baroreflex (CSB), skin conductance level (SC), cardiac sympathetic index (CSI) and mean blood pressure (MBP). Visceral pain was induced by balloon distension in proximal (PB) and distal (DB) oesophagus and somatic pain by nail-bed pressure (NBP). Eight painful stimuli were delivered at each site and unpleasantness and intensity measured. Personality was profiled with the Big Five inventory. (1) Oesophageal intubation evoked "fight-flight" responses: HR and sympathetic (CSI, SC, MBP) elevation with parasympathetic (CVT) withdrawal (p<0.05). (2) Pain at all sites evoked novel parasympathetic/sympathetic co-activation with elevated HR but vasodepression (all p<0.05). (3) Personality traits correlated with slope of distal oesophageal pain-related CVT changes wherein more neurotic-introvert subjects had greater positive pain-related CVT slope change (neuroticism r 0.8, p<0.05; extroversion r -0.5, p<0.05). Pain-evoked heart rate increases were mediated by parasympathetic and sympathetic co-activation - a novel finding in humans but recently described in mammals too. Visceral pain-related parasympathetic change correlated with personality. ANS defence responses are nuanced and may relate to personality type for visceral pain. Clinical relevance of these findings warrants further exploration.

Fatalities after taking ibogaine in addiction treatment could be related to sudden cardiac death caused by autonomic dysfunction.

PubMed

Maas, U; Strubelt, S

2006-01-01

Ibogaine is the most important alkaloid of the Central African Iboga-shrub. It is the central drug in Gabonian initiation ceremonies in which it is used to cause a near-death experience. In Western countries it is used in private clinics to treat addiction. However, in the United States and most European countries it is classified as an illegal drug because at least eight persons have died after having taken Ibogaine. These fatalities occurred in most cases several days after ingestion or following the intake of very small doses. There is no conclusive explanation at the present time for these deaths. We hypothesize, that these deaths may be a result of cardiac arrhythmias, caused by a dysregulation of the autonomic nervous system. Ibogaine affects the autonomic nervous system by influencing several neurotransmitter-systems and the fastigial nucleus. The cerebellar nucleus responds to small doses with a stimulation of the sympathetic system, leading to a fight or flight reaction. High doses, however, lead to a vagal dominance: a "feigned death". The risk of cardiac arrhythmias is increased in situations of sympathetic stimulation or coincidence of a high parasympathetic tonus and a left-sided sympathetic stimulation. This could occur under influence of small doses of ibogaine and also at times of exhaustion with a high vagal tonus, when sudden fear reactions could cause a critical left-sided sympathetic stimulation. Gabonian healers prevent these risks by isolating their patients from normal life and by inducing a trance-state with right-hemispheric and vagal dominance for several days.

Animal model of neuropathic tachycardia syndrome

NASA Technical Reports Server (NTRS)

Carson, R. P.; Appalsamy, M.; Diedrich, A.; Davis, T. L.; Robertson, D.

2001-01-01

Clinically relevant autonomic dysfunction can result from either complete or partial loss of sympathetic outflow to effector organs. Reported animal models of autonomic neuropathy have aimed to achieve complete lesions of sympathetic nerves, but incomplete lesions might be more relevant to certain clinical entities. We hypothesized that loss of sympathetic innervation would result in a predicted decrease in arterial pressure and a compensatory increase in heart rate. Increased heart rate due to loss of sympathetic innervation is seemingly paradoxical, but it provides a mechanistic explanation for clinical autonomic syndromes such as neuropathic postural tachycardia syndrome. Partially dysautonomic animals were generated by selectively lesioning postganglionic sympathetic neurons with 150 mg/kg 6-hydroxydopamine hydrobromide in male Sprague-Dawley rats. Blood pressure and heart rate were monitored using radiotelemetry. Systolic blood pressure decreased within hours postlesion (Delta>20 mm Hg). Within 4 days postlesion, heart rate rose and remained elevated above control levels. The severity of the lesion was determined functionally and pharmacologically by spectral analysis and responsiveness to tyramine. Low-frequency spectral power of systolic blood pressure was reduced postlesion and correlated with the diminished tyramine responsiveness (r=0.9572, P=0.0053). The tachycardia was abolished by treatment with the beta-antagonist propranolol, demonstrating that it was mediated by catecholamines acting on cardiac beta-receptors. Partial lesions of the autonomic nervous system have been hypothesized to underlie many disorders, including neuropathic postural tachycardia syndrome. This animal model may help us better understand the pathophysiology of autonomic dysfunction and lead to development of therapeutic interventions.

Renal sympathetic denervation in therapy resistant hypertension - pathophysiological aspects and predictors for treatment success

PubMed Central

Fengler, Karl; Rommel, Karl Philipp; Okon, Thomas; Schuler, Gerhard; Lurz, Philipp

2016-01-01

Many forms of human hypertension are associated with an increased systemic sympathetic activity. Especially the renal sympathetic nervous system has been found to play a prominent role in this context. Therefore, catheter-interventional renal sympathetic denervation (RDN) has been established as a treatment for patients suffering from therapy resistant hypertension in the past decade. The initial enthusiasm for this treatment was markedly dampened by the results of the Symplicity-HTN-3 trial, although the transferability of the results into clinical practice to date appears to be questionable. In contrast to the extensive use of RDN in treating hypertensive patients within or without clinical trial settings over the past years, its effects on the complex pathophysiological mechanisms underlying therapy resistant hypertension are only partly understood and are part of ongoing research. Effects of RDN have been described on many levels in human trials: From altered systemic sympathetic activity across cardiac and metabolic alterations down to changes in renal function. Most of these changes could sustainably change long-term morbidity and mortality of the treated patients, even if blood pressure remains unchanged. Furthermore, a number of promising predictors for a successful treatment with RDN have been identified recently and further trials are ongoing. This will certainly help to improve the preselection of potential candidates for RDN and thereby optimize treatment outcomes. This review summarizes important pathophysiologic effects of renal denervation and illustrates the currently known predictors for therapy success. PMID:27621771

Renal Sympathetic Denervation in Rats Ameliorates Cardiac Dysfunction and Fibrosis Post-Myocardial Infarction Involving MicroRNAs

PubMed Central

Zheng, Xiaoxin; Li, Xiaoyan; Lyu, Yongnan; He, Yiyu; Wan, Weiguo; Jiang, Xuejun

2016-01-01

Background The role of renal sympathetic denervation (RSD) in ameliorating post-myocardial infarction (MI) left ventricular (LV) fibrosis via microRNA-dependent regulation of connective tissue growth factor (CTGF) remains unknown. Material/Methods MI and RSD were induced in Sprague–Dawley rats by ligating the left coronary artery and denervating the bilateral renal nerves, respectively. Norepinephrine, renin, angiotensin II and aldosterone in plasma, collagen, microRNA21, microRNA 101a, microRNA 133a and CTGF in heart tissue, as well as cardiac function were evaluated six weeks post-MI. Results In the RSD group, parameters of cardiac function were significantly improved as evidenced by increased LV ejection fraction (p<0.01), LV end-systolic diameter (p<0.01), end-diastolic diameter (p<0.05), LV systolic pressure (p<0.05), maximal rate of pressure rise and decline (dP/dtmax and dP/dtmin, p<0.05), and decreased LV end-diastolic pressure (p<0.05) when compared with MI rats. Further, reduced collagen deposition in peri-infarct myocardium was observed in RSD-treated rats along with higher microRNA101a and microRNA133a (p<0.05) and lower microRNA21 expression (p<0.01) than in MI rats. CTGF mRNA and protein levels were decreased in LV following RSD (p<0.01), accompanied by decreased expression of norepinephrine, renin, angiotensin II and aldosterone in plasma (p<0.05) compared with untreated MI rats. Conclusions The potential therapeutic effects of RSD on post-MI LV fibrosis may be partly mediated by inhibition of CTGF expression via upregulation of microRNA 101a and microRNA 133a and downregulation of microRNA21. PMID:27490896

Dual agonist occupancy of AT1-R–α2C-AR heterodimers results in atypical Gs-PKA signaling

PubMed Central

Bellot, Morgane; Galandrin, Ségolène; Boularan, Cédric; Matthies, Heinrich J; Despas, Fabien; Denis, Colette; Javitch, Jonathan; Mazères, Serge; Sanni, Samra Joke; Pons, Véronique; Seguelas, Marie-Hélène; Hansen, Jakob L; Pathak, Atul; Galli, Aurelio; Sénard, Jean-Michel; Galés, Céline

2015-01-01

Hypersecretion of norepinephrine (NE) and angiotensin II (AngII) is a hallmark of major prevalent cardiovascular diseases that contribute to cardiac pathophysiology and morbidity. Herein, we explore whether heterodimerization of presynaptic AngII AT1 receptor (AT1-R) and NE α2C-adrenergic receptor (α2C-AR) could underlie their functional cross-talk to control NE secretion. Multiple bioluminescence resonance energy transfer and protein complementation assays allowed us to accurately probe the structures and functions of the α2C-AR–AT1-R dimer promoted by ligand binding to individual protomers. We found that dual agonist occupancy resulted in a conformation of the heterodimer different from that induced by active individual protomers and triggered atypical Gs-cAMP–PKA signaling. This specific pharmacological signaling unit was identified in vivo to promote not only NE hypersecretion in sympathetic neurons but also sympathetic hyperactivity in mice. Thus, we uncovered a new process by which GPCR heterodimerization creates an original functional pharmacological entity and that could constitute a promising new target in cardiovascular therapeutics. PMID:25706338

A rare case of recurrent vasodepressive attacks of 2-hours duration: analysis of the mechanism by muscle sympathetic nerve activity recording.

PubMed

Yatomi, A; Iguchi, A; Uemura, K; Sakamoto, N; Iwase, S; Mano, T

1989-03-01

Muscle sympathetic nerve activity was recorded in a 57-year-old male patient suffering from severe hypotensive attacks with bradycardia for 10 years. Continuous blood pressure recording demonstrated frequent drastic falls in pressure. Disappearance and reappearance of muscle sympathetic nerve activity coincided with the onset and termination of attacks. Awakening from sleep or emotional and/or cardiovascular stress seems to trigger hypotension. Cardiac pacemaker was not useful in limiting the attack, because right ventricular pacing caused abrupt falls in both blood pressure and heart rate.

Exercise at depth alters bradycardia and incidence of cardiac anomalies in deep-diving marine mammals.

PubMed

Williams, Terrie M; Fuiman, Lee A; Kendall, Traci; Berry, Patrick; Richter, Beau; Noren, Shawn R; Thometz, Nicole; Shattock, Michael J; Farrell, Edward; Stamper, Andy M; Davis, Randall W

2015-01-16

Unlike their terrestrial ancestors, marine mammals routinely confront extreme physiological and physical challenges while breath-holding and pursuing prey at depth. To determine how cetaceans and pinnipeds accomplish deep-sea chases, we deployed animal-borne instruments that recorded high-resolution electrocardiograms, behaviour and flipper accelerations of bottlenose dolphins (Tursiops truncatus) and Weddell seals (Leptonychotes weddellii) diving from the surface to >200 m. Here we report that both exercise and depth alter the bradycardia associated with the dive response, with the greatest impacts at depths inducing lung collapse. Unexpectedly, cardiac arrhythmias occurred in >73% of deep, aerobic dives, which we attribute to the interplay between sympathetic and parasympathetic drivers for exercise and diving, respectively. Such marked cardiac variability alters the common view of a stereotypic 'dive reflex' in diving mammals. It also suggests the persistence of ancestral terrestrial traits in cardiac function that may help explain the unique sensitivity of some deep-diving marine mammals to anthropogenic disturbances.

[A basis for application of cardiac contractility variability in the Evaluation and assessment of exercise and fitness].

PubMed

Bu, Bin; Wang, Aihua; Han, Haijun; Xiao, Shouzhong

2010-06-01

Cardiac contractility variability (CCV) is a new concept which is introduced in the research field of cardiac contractility in recent years, that is to say, there are some disparities between cardiac contractilities when heart contracts. The changing signals of cardiac contractility contain a plenty of information on the cardiovascular function and disorder. In order to collect and analyze the message, we could quantitatively evaluate the tonicity and equilibrium of cardiac sympathetic nerve and parasympathetic nerve, and the effects of bio-molecular mechanism on the cardiovascular activities. By analyzing CCV, we could further understand the background of human being's heritage characteristics, nerve types, the adjusting mechanism, the molecular biology, and the adjustment of cardiac automatic nerve. With the development of the computing techniques, the digital signal processing method and its application in medical field, this analysis has been progressing greatly. By now, the assessment of CCV, just like the analysis of heart rate variability, is mainly via time domain and frequency domain analysis. CCV is one of the latest research fields in human cardiac signals being scarcely reported in the field of sports medicine; however, its research progresses are of important value for cardiac physiology and pathology in sports medicine and rehabilitation medicine.

β-Adrenergic or parasympathetic inhibition, heart rate and cardiac output during normoxic and acute hypoxic exercise in humans

PubMed Central

Hopkins, Susan R; Bogaard, Harm J; Niizeki, Kyuichi; Yamaya, Yoshiki; Ziegler, Michael G; Wagner, Peter D

2003-01-01

Acute hypoxia increases heart rate (HR) and cardiac output () at a given oxygen consumption () during submaximal exercise. It is widely believed that the underlying mechanism involves increased sympathetic activation and circulating catecholamines acting on cardiac β receptors. Recent evidence indicating a continued role for parasympathetic modulation of HR during moderate exercise suggests that increased parasympathetic withdrawal plays a part in the increase in HR and during hypoxic exercise. To test this, we separately blocked the β-sympathetic and parasympathetic arms of the autonomic nervous system (ANS) in six healthy subjects (five male, one female; mean ± s.e.m. age = 31.7 ± 1.6 years, normoxic maximal () = 3.1 ± 0.3 l min−1) during exercise in conditions of normoxia and acute hypoxia (inspired oxygen fraction = 0.125) to . Data were collected on different days under the following conditions: (1)control, (2) after 8.0 mg propranolol I.V. and (3) after 0.8 mg glycopyrrolate I.V. was measured using open-circuit acetylene uptake. Hypoxia increased venous [adrenaline] and [noradrenaline] but not [dopamine] at a given (P < 0.05, P < 0.01 and P = 0.2, respectively). HR/ and / increased during hypoxia in all three conditions (P < 0.05). Unexpectedly, the effects of hypoxia on HR and were not significantly different from control with either β-sympathetic or parasympathetic inhibition. These data suggest that although acute exposure to hypoxia increases circulating [catecholamines], the effects of hypoxia on HR and do not necessarily require intact cardiac muscarinic and β receptors. It may be that cardiac α receptors play a primary role in elevating HR and during hypoxic exercise, or perhaps offer an alternative mechanism when other ANS pathways are blocked. PMID:12766243

Sympathomimetic Effects of Acute E-Cigarette Use: Role of Nicotine and Non-Nicotine Constituents.

PubMed

Moheimani, Roya S; Bhetraratana, May; Peters, Kacey M; Yang, Benjamin K; Yin, Fen; Gornbein, Jeffrey; Araujo, Jesus A; Middlekauff, Holly R

2017-09-20

Chronic electronic (e) cigarette users have increased resting cardiac sympathetic nerve activity and increased susceptibility to oxidative stress. The purpose of the present study is to determine the role of nicotine versus non-nicotine constituents in e-cigarette emissions in causing these pathologies in otherwise healthy humans. Thirty-three healthy volunteers who were not current e-cigarette or tobacco cigarette smokers were studied. On different days, each participant used an e-cigarette with nicotine, an e-cigarette without nicotine, or a sham control. Cardiac sympathetic nerve activity was determined by heart rate variability, and susceptibility to oxidative stress was determined by plasma paraoxonase activity. Following exposure to the e-cigarette with nicotine, but not to the e-cigarette without nicotine or the sham control, there was a significant and marked shift in cardiac sympathovagal balance towards sympathetic predominance. The decrease in high-frequency component and the increases in the low-frequency component and the low-frequency to high-frequency ratio were significantly greater following exposure to the e-cigarette with nicotine compared with exposure to the e-cigarette without nicotine or to sham control. Oxidative stress, as estimated by plasma paraoxonase, did not increase following any of the 3 exposures. The acute sympathomimetic effect of e-cigarettes is attributable to the inhaled nicotine, not to non-nicotine constituents in e-cigarette aerosol, recapitulating the same heart rate variability pattern associated with increased cardiac risk in multiple populations with and without known cardiac disease. Evidence of oxidative stress, as estimated by plasma paraoxonase activity, was not uncovered following acute e-cigarette exposure. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Cardiac autonomic function and hot flashes among perimenopausal and postmenopausal women.

PubMed

Gibson, Carolyn J; Mendes, Wendy Berry; Schembri, Michael; Grady, Deborah; Huang, Alison J

2017-07-01

Abnormalities in autonomic function are posited to play a pathophysiologic role in menopausal hot flashes. We examined relationships between resting cardiac autonomic activity and hot flashes in perimenopausal and postmenopausal women. Autonomic function was assessed at baseline and 12 weeks among perimenopausal and postmenopausal women (n = 121, mean age 53 years) in a randomized trial of slow-paced respiration for hot flashes. Pre-ejection period (PEP), a marker of sympathetic activation, was measured with impedance cardiography. Respiratory sinus arrhythmia (RSA), a marker of parasympathetic activation, was measured with electrocardiography. Participants self-reported hot flash frequency and severity in 7-day symptom diaries. Analysis of covariance models were used to relate autonomic function and hot flash frequency and severity at baseline, and to relate changes in autonomic function to changes in hot flash frequency and severity over 12 weeks, adjusting for age, body mass index, and intervention assignment. PEP was not associated with hot flash frequency or severity at baseline or over 12 weeks (P > 0.05 for all). In contrast, there was a trend toward greater frequency of moderate-to-severe hot flashes with higher RSA at baseline (β = 0.43, P = 0.06), and a positive association between change in RSA and change in frequency of moderate-to-severe hot flashes over 12 weeks (β = 0.63, P = 0.04). Among perimenopausal and postmenopausal women with hot flashes, variations in hot flash frequency and severity were not explained by variations in resting sympathetic activation. Greater parasympathetic activation was associated with more frequent moderate-to-severe hot flashes, which may reflect increased sensitivity to perceiving hot flashes.

THE EFFECTS OF NON-FUNCTIONAL OVERREACHING AND OVERTRAINING ON AUTONOMIC NERVOUS SYSTEM FUNCTION IN HIGHLY TRAINED ATHLETES.

PubMed

Kajaia, T; Maskhulia, L; Chelidze, K; Akhalkatsi, V; Kakhabrishvili, Z

2017-03-01

Aim of the study was to compare the ANS functioning, as measured by heart rate variability (HRV), in athletes with non-functional overreaching (NFO) and overtraining syndrome (OTS) and in athletes without NFO/OTS. In 43 athletes with NFO/OTS, 40 athletes without NFO/OTS, as well as in 35 sedentary subjects the ANS function was evaluated with the Autonomic Balance Test, based on the HRV analysis of resting heart rate recordings. Results of the study show lower HRV and lower vagal influence along with increased sympathetic cardiovascular control in athletes with non-functional overreaching and particularly in athletes with overtraining, than in highly trained athletes without NFO/OTS. "Stress Response" in athletes with NFO, as well as in some athletes with OTS, showing sympathetic dominance, considered as a sign of physical or mental fatigue and chronic stress, whereas "Total Autonomic Dystonia" in most of the athletes with OTS (67%) reflects more advanced stage of maladaptation associated with depressed regulatory function of the ANS, both sympathetic, as well as vagal influences. Most frequently NFO and OTS were seen in wrestling, which needs further investigation and regular medical monitoring. Thus, results of the study show progression of autonomic imbalance and depression of regulatory function of the autonomic nervous system in athletes with OTS. The cardiac autonomic imbalance observed in overtrained athletes implies changes in HRV and therefore would consider that heart rate variability may provide useful information in detection of overtraining in athletes and can be a valuable adjacent tool for optimising athlete's training program as well as for timely diagnosis and prevention of progression of NFO/OTS.

Disruption of intracardiac flow patterns in the newborn infant.

PubMed

Groves, Alan M; Durighel, Giuliana; Finnemore, Anna; Tusor, Nora; Merchant, Nazakat; Razavi, Reza; Hajnal, Jo V; Edwards, A David

2012-04-01

Consistent patterns of rotational intracardiac flow have been demonstrated in the healthy adult human heart. Intracardiac rotational flow patterns are hypothesized to assist in the maintenance of kinetic energy of inflowing blood, augmenting cardiac function. Newborn cardiac function is known to be suboptimal secondary to decreased receptor number and sympathetic innervation, increased afterload, and increased reliance on atrial contraction to support ventricular filling. Patterns of intracardiac flow in the newborn have not previously been examined. Whereas 5 of the 13 infants studied showed significant evidence of rotational flow within the right atrium, 8 infants showed little or no rotational flow. Presence or absence of rotational flow was not related to gestational age, birth weight, postnatal age, atrial size, or image quality. Despite absence of intra-atrial rotational flow, atrioventricular valve flow into the left and right ventricles later in the cardiac cycle could be seen, suggesting that visualization techniques were adequate. While further study is required to assess its exact consequences on cardiac mechanics and energetics, disruption to intracardiac flow patterns could be another contributor to the multifactorial sequence that produces newborn circulatory failure. We studied 13 newborn infants, using three-dimensional (3D) cardiac magnetic resonance phase-contrast imaging (spatial resolution 0.84 mm, temporal resolution 22.6 ms) performed without sedation/anesthesia.

Valsalva's maneuver revisited: a quantitative method yielding insights into human autonomic control

NASA Technical Reports Server (NTRS)

Smith, M. L.; Beightol, L. A.; Fritsch-Yelle, J. M.; Ellenbogen, K. A.; Porter, T. R.; Eckberg, D. L.

1996-01-01

Seventeen healthy supine subjects performed graded Valsalva maneuvers. In four subjects, transesophageal echographic aortic cross-sectional areas decreased during and increased after straining. During the first seconds of straining, when aortic cross-sectional area was declining and peripheral arterial pressure was rising, peroneal sympathetic muscle neurons were nearly silent. Then, as aortic cross-sectional area and peripheral pressure both declined, sympathetic muscle nerve activity increased, in proportion to the intensity of straining. Poststraining arterial pressure elevations were proportional to preceding increases of sympathetic activity. Sympathetic inhibition after straining persisted much longer than arterial and right atrial pressure elevations. Similarly, R-R intervals changed in parallel with peripheral arterial pressure, until approximately 45 s after the onset of straining, when R-R intervals were greater and arterial pressures were smaller than prestraining levels. Our conclusions are as follows: opposing changes of carotid and aortic baroreceptor inputs reduce sympathetic muscle and increase vagal cardiac motor neuronal firing; parallel changes of barorsensory inputs provoke reciprocal changes of sympathetic and direct changes of vagal firing; and pressure transients lasting only seconds reset arterial pressure-sympathetic and -vagal response relations.

Effects of chronic treatment with cyclooxygenase inhibitor, indomethacin on oral contraceptive-induced high blood pressure in female rats.

PubMed

Olatunji, L A; Soladoye, A O

2010-03-01

The present study sought to investigate the effects of prostaglandins synthesis inhibition with indomethacin on blood pressure, heart rate, cardiac weight, plasma electrolytes and cardiovascular responses to arterial baroreceptor stimulation in Oral contraceptive (OC) treated female Sprague-Dawley rats. Oral administration of synthetic oestrogen, ethinyl oestradiol in combination with progestogen, norgestrel for ten weeks significantly increased blood pressure and cardiac weight compared with those of the control rats. Concomitant treatment with indomethacin significantly abrogated increase in blood pressure but did not affect the increase in cardiac weight induced by OC. Heart rate, plasma sodium and potassium concentrations were not affected by OC and/or indomethacin treatment. OC treatment did not alter sympathetic-mediated pressor and tachycardiac responses caused by bilateral carotid baroreceptors unloading. However, these responses were significantly attenuated by indomethacin treatment. These results demonstrated that rat model of OC-induced high blood pressure developed cardiac hypertrophy that is not associated with altered sympathetic-mediated cardiovascular responses to arterial baroreceptor stimulation. The finding that indomethacin prevented OC-induced high blood pressure, but not associated cardiac hypertrophy implies that synthesis of prostaglandins may be an important determinant of OC-induced hypertension, while associated cardiac hypertrophy may not be pressure overload-dependent.

Anisotropic Reinforcement of Acute Anteroapical Infarcts Improves Pump Function

PubMed Central

Fomovsky, Gregory M.; Clark, Samantha A.; Parker, Katherine M.; Ailawadi, Gorav; Holmes, Jeffrey W.

2012-01-01

Background We hypothesize that a therapy that improves LV pump function early after infarction should decrease the need for compensation through sympathetic activation and dilation, thereby reducing the risk of developing heart failure. The mechanical properties of healing myocardial infarcts are an important determinant of left ventricular (LV) function, yet improving function by altering infarct properties has proven unexpectedly difficult. Using a computational model, we recently predicted that stiffening a large anterior infarct anisotropically (in only one direction) would improve LV function, while isotropic stiffening, the focus of previous studies and therapies, would not. The goal of this study was to test the novel strategy of anisotropic infarct reinforcement. Methods and Results We tested the effects of anisotropic infarct reinforcement in 10 open-chest dogs with large anteroapical infarcts that depressed LV pump function. We measured regional mechanics, LV volumes, and cardiac output at a range of preloads at Baseline, 45 minutes after coronary ligation (Ischemia), and 30 minutes later, following surgical reinforcement in the longitudinal direction (Anisotropic). Ischemia shifted the end-systolic pressure-volume relationship (ESPVR) and cardiac output curves rightward, decreasing cardiac output at matched end-diastolic pressure (EDP) by 44%. Anisotropic reinforcement significantly improved systolic function without impairing diastolic function, recovering half the deficit in overall LV function. Conclusions We conclude that anisotropic reinforcement is a promising new approach to improving LV function following a large myocardial infarction. PMID:22665716

Cardiovascular aspects of Parkinson disease.

PubMed

Goldstein, D S

2006-01-01

This chapter provides an update about cardiovascular aspects of Parkinson disease (PD), with the following topics: (1) Orthostatic hypotension (OH) as an early finding in PD; (2) neurocirculatory abnormalities in PD + OH independent of levodopa treatment; (3) cardiac and extracardiac noradrenergic denervation in PD + OH; (4) progressive loss of cardiac sympathetic innervation in PD without OH.

Role of adrenal hormones in the synthesis of noradrenaline in cardiac sympathetic neurones

PubMed Central

Bhagat, B.

1969-01-01

1. Adrenalectomy or adrenal demedullation affected neither the levels of endogenous catecholamines in the rat heart nor the accumulation of 3H-noradrenaline 1 hr after its intravenous administration. 2. Twenty-four hours after intravenous administration of labelled amine, however, its retention was markedly reduced in the heart of adrenalectomized or demedullated rats. Ganglionic blockade prevented this reduction. 3. Rate calculations from the decline of catecholamine levels after blockade of synthesis with α-methyl-tyrosine showed that cardiac synthesis of noradrenaline increased about four-fold after demedullation and about three-fold after adrenalectomy. This increase in synthesis may compensate for the loss of circulating catecholamines. 4. There was no change in catechol-o-methyl-transferase activity, but monoamine oxidase activity was increased in the homogenates of the heart of adrenalectomized and demedullated rats. The increase in the cardiac monoamine oxidase activity was markedly greater in the adrenalectomized rats than in the demedullated rats. 5. It is suggested that adrenal cortex insufficiency may modulate the rate of synthesis of noradrenaline and monoamine oxidase activity in cardiac sympathetic neurones. PMID:5360339

Cardiovascular Adaptation to Stress

DTIC Science & Technology

1979-05-01

sympathetic activity, suited in a proportionately larger increase in cardiac The concept that the background level of sympathetic output than arterial...simultaneously be reduced during disten- hypoxia. flow autoregulation occurred. In these con- sion. This concept is supported by the work of Levy et al. scious...of Pharmacology, University of Texa Healh Science Center, San Antonio, Texas 78284 S’rm r, H. 0., D. F. PlTERSON, AND V. S. BISHOP. Car- their

Focal myocardial infarction induces global remodeling of cardiac sympathetic innervation: neural remodeling in a spatial context

PubMed Central

Ajijola, Olujimi A.; Yagishita, Daigo; Patel, Krishan J.; Vaseghi, Marmar; Zhou, Wei; Yamakawa, Kentaro; So, Eileen; Lux, Robert L.; Mahajan, Aman

2013-01-01

Myocardial infarction (MI) induces neural and electrical remodeling at scar border zones. The impact of focal MI on global functional neural remodeling is not well understood. Sympathetic stimulation was performed in swine with anteroapical infarcts (MI; n = 9) and control swine (n = 9). A 56-electrode sock was placed over both ventricles to record electrograms at baseline and during left, right, and bilateral stellate ganglion stimulation. Activation recovery intervals (ARIs) were measured from electrograms. Global and regional ARI shortening, dispersion of repolarization, and activation propagation were assessed before and during sympathetic stimulation. At baseline, mean ARI was shorter in MI hearts than control hearts (365 ± 8 vs. 436 ± 9 ms, P < 0.0001), dispersion of repolarization was greater in MI versus control hearts (734 ± 123 vs. 362 ± 32 ms2, P = 0.02), and the infarcted region in MI hearts showed longer ARIs than noninfarcted regions (406 ± 14 vs. 365 ± 8 ms, P = 0.027). In control animals, percent ARI shortening was greater on anterior than posterior walls during right stellate ganglion stimulation (P = 0.0001), whereas left stellate ganglion stimulation showed the reverse (P = 0.0003). In infarcted animals, this pattern was completely lost. In 50% of the animals studied, sympathetic stimulation, compared with baseline, significantly altered the direction of activation propagation emanating from the intramyocardial scar during pacing. In conclusion, focal distal anterior MI alters regional and global pattern of sympathetic innervation, resulting in shorter ARIs in infarcted hearts, greater repolarization dispersion, and altered activation propagation. These conditions may underlie the mechanisms by which arrhythmias are initiated when sympathetic tone is enhanced. PMID:23893167

Cardiorespiratory Fitness and Cardiac Autonomic Function in Diabetes.

PubMed

Röhling, Martin; Strom, Alexander; Bönhof, Gidon J; Roden, Michael; Ziegler, Dan

2017-10-23

This review summarizes the current knowledge on the relationship of physical activity, exercise, and cardiorespiratory fitness (CRF) with cardiovascular autonomic neuropathy (CAN) based on epidemiological, clinical, and interventional studies. The prevalence of CAN increases with age and duration of diabetes. Further risk factors for CAN comprise poor glycemic control, dyslipidemia, abdominal obesity, hypertension, and the presence of diabetic complications. CAN has been also linked to reduced CRF. We recently showed that CRF parameters (e.g., maximal oxidative capacity or oxidative capacity at the anaerobic threshold) are associated with cardiac autonomic function in patients recently diagnosed with type 1 or type 2 diabetes. Exercise interventions have shown that physical activity can increase cardiovagal activity and reduce sympathetic overactivity. In particular, long-term and regularly, but also supervised, performed endurance and high-intense and high-volume exercise improves cardiac autonomic function in patients with type 2 diabetes. By contrast, the evidence in those with type 1 diabetes and also in individuals with prediabetes or metabolic syndrome is weaker. Overall, the studies reviewed herein addressing the question whether favorably modulating the autonomic nervous system may improve CRF during exercise programs support the therapeutic concept to promote physical activity and to achieve physical fitness. However, high-quality exercise interventions, especially in type 1 diabetes and metabolic syndrome including prediabetes, are further required to better understand the relationship between physical activity, fitness, and cardiac autonomic function.

Circulatory response and autonomic nervous activity during gum chewing.

PubMed

Hasegawa, Yoko; Sakagami, Joe; Ono, Takahiro; Hori, Kazuhiro; Zhang, Min; Maeda, Yoshinobu

2009-08-01

Mastication has been proven to enhance the systemic circulation, with circulatory responses seeming to be largely regulated by autonomic nervous activity via a more complex regulatory system than those of other activities. However, few studies have examined the relationships between changes in autonomic nervous activity and the systemic circulation that are induced by masticatory movement. We investigated changes in the systemic circulation and autonomic nervous activity during gum chewing to clarify the influence of mastication. Electrocardiograms, arterial blood pressure, and masseter electromyograms were taken while chewing gum continuously as indicators of systemic circulation in 10 healthy subjects with normal dentition. Cardiac sympathetic activity and vagus nervous activity, as well as vasomotor sympathetic nervous activity, were evaluated by fluctuation analysis of heart rate and blood pressure. Repeated analysis of variance and multiple comparisons were performed to determine chronological changes in each indicator during gum chewing. Gum chewing increased the heart rate and the mean arterial pressure. Although cardiac sympathetic activity and vagus nervous activity showed significant changes, vasomotor sympathetic nervous activity did not. These results suggest that changes in the autonomic nervous activity of the heart are mainly involved in the enhancement of systemic circulation with gum chewing. This explains some characteristics of autonomic nervous regulation in masticatory movement.

Effect of HeartMate left ventricular assist device on cardiac autonomic nervous activity.

PubMed

Kim, S Y; Montoya, A; Zbilut, J P; Mawulawde, K; Sullivan, H J; Lonchyna, V A; Terrell, M R; Pifarré, R

1996-02-01

Clinical performance of a left ventricular assist device is assessed via hemodynamic parameters and end-organ function. This study examined effect of a left ventricular assist device on human neurophysiology. This study evaluated the time course change of cardiac autonomic activity of 3 patients during support with a left ventricular assist device before cardiac transplantation. Cardiac autonomic activity was determined by power spectral analysis of short-term heart rate variability. The heart rate variability before cardiac transplantation was compared with that on the day before left ventricular assist device implantation. The standard deviation of the mean of the R-R intervals of the electrocardiogram, an index of vagal activity, increased to 27 +/- 7 ms from 8 +/- 0.6 ms. The modulus of power spectral components increased. Low frequency (sympathetic activity) and high frequency power (vagal activity) increased by a mean of 9 and 22 times of each baseline value (low frequency power, 5.2 +/- 3.0 ms2; high frequency power, 2.1 +/- 0.7 ms2). The low over high frequency power ratio decreased substantially, indicating an improvement of cardiac sympatho-vagal balance. The study results suggest that left ventricular assist device support before cardiac transplantation may exert a favorable effect on cardiac autonomic control in patients with severe heart failure.

Cardio-oncology: the Nuclear Option.

PubMed

Alvarez, Jorge A; Russell, Raymond R

2017-04-01

Cardio-oncology focuses increased effort to decrease cancer treatment-related cardiotoxicity while continuing to improve outcomes. We sought to synthesize the latest in nuclear cardiology as it pertains to the assessment of left ventricular function in preventative guidelines and comparison to other modalities, novel molecular markers of pre-clinical cardiotoxicity, and its role in cardiac amyloid diagnosis. Planar ERNA (equilibrium radionuclide angiocardiography) provides a reliable and proven means of monitoring and preventing anthracycline cardiotoxicity, and SPECT ERNA using solid-state gamma cameras may provide reproducible assessments of left ventricular function with reduced radiation exposure. While certain chemotherapeutics have vascular side effects, the use of stress perfusion imaging has still not been adequately studied for routine use. Similarly, markers of apoptosis, inflammation, and sympathetic nerve dysfunction are promising, but are still not ready for uniform usage. SPECT tracers can assist in nonbiopsy diagnosis of cardiac amyloid. Nuclear cardiology is a significant contributor to the multimodality approach to cardio-oncology.

Cardiac effects produced by long-term stimulation of thoracic autonomic ganglia or nerves: implications for interneuronal interactions within the thoracic autonomic nervous system.

PubMed

Butler, C; Watson-Wright, W M; Wilkinson, M; Johnstone, D E; Armour, J A

1988-03-01

Electrical stimulation of an acutely decentralized stellate or middle cervical ganglion or cardiopulmonary nerve augments cardiac chronotropism or inotropism; as the stimulation continues there is a gradual reduction of this augmentation following the peak response, i.e., an inhibition of augmentation. The amount of this inhibition was found to be dependent upon the region of the heart investigated and the neural structure stimulated. The cardiac parameters which were augmented the most displayed the greatest inhibition. Maximum augmentation or inhibition occurred, in most instances, when 5-20 Hz stimuli were used. Inhibition of augmentation was overcome when the stimulation frequency was subsequently increased or following the administration of nicotine or tyramine, indicating that the inhibition was not primarily due to the lack of availability of noradrenaline in the nerve terminals of the efferent postganglionic sympathetic neurons. Furthermore, as infusions of isoproterenol or noradrenaline during the period of inhibition could still augment cardiac responses, whereas during the early peak responses they did not, the inhibition of augmentation does not appear to be due primarily to down regulation of cardiac myocyte beta-adrenergic receptors. The inhibition was modified by hexamethonium but not by phentolamine or atropine. Inhibition occurred when all ipsilateral cardiopulmonary nerves connected with acutely decentralized middle cervical and stellate ganglia were stimulated, whereas significant inhibition did not occur when these nerves were stimulated after they had been disconnected from the ipsilateral decentralized ganglia. Taken together these data indicate that the inhibition of cardiac augmentation which occurs during relatively long-term stimulation of intrathoracic sympathetic neural elements is due in large part to nicotinic cholinergic synaptic mechanisms that lie primarily in the major thoracic autonomic ganglia. They also indicate that long-term stimulation in intrathoracic sympathetic neural elements with frequencies as low as 2 Hz may augment the heart as much as higher stimulation frequencies, depending upon the structure stimulated and the cardiovascular parameter monitored.

Pathogenesis of sudden death following water immersion (immersion syndrome)

NASA Technical Reports Server (NTRS)

Buhring, M.; Spies, H. F.

1981-01-01

Sympathetic activity under cold stress is investigated. Predominantly vagal cardio-depressive reflexes are discussed besides currently known mechanisms of sudden death after water immersion. Pronounced circulatory centralization in diving animals as well as following exposure in cold water indicates additional sympathetic activity. In cold water baths of 15 C, measurements indicate an increase in plasma catecholamine levels by more than 300 percent. This may lead to cardiac arrhythmias by the following mechanisms: cold water essentially induces sinus bradycardia; brady-and tachycardiarrhythmias may supervene as secondary complications; sinusbradycardia may be enhanced by sympathetic hypertonus. Furthermore, ectopic dysrhythmias are liable to be induced by the strictly sympathetic innervation of the ventricle. Myocardial ischemia following a rise in peripheral blood pressure constitutes another arrhythmogenic factor. Some of these reactions are enhanced by alcohol intoxication.

Low Baseline Sympathetic Tone Correlates to a Greater Blood Pressure Change in the Cold Pressor Test.

PubMed

Youssef, Marylen; Ghassemi, Azadeh; Carvajal Gonczi, Catalina Marysol; Kugathasan, Thiffya Arabi; Kilgour, Robert D; Darlington, Peter J

2018-06-01

The cold pressor test (CPT) involves acute hand or foot exposure to cold water. CPT hyper-responders have unique traits, including risk of hypertension and a greater vasoconstrictor reserve and g force tolerance compared to hypo-responders. The purpose of this study was to uncover differences in cardiovascular and sympathetic biomarkers between responder types. Healthy volunteers (N = 30) submerged one hand into cold water (3.3 ± 0.8°C) for 5 min. Blood pressure, heart rate, cardiac output, and cardiac parameters were recorded using an automated monitor, impedance cardiography, and a beat-to-beat monitoring system. We analyzed for salivary α-amylase (SαA), which is a convenient biomarker of the sympathetic nervous system. Subjects were stratified post hoc into hyper-responders (≥ 22 mmHg) and hypo-responders (< 22 mmHg) based on change in systolic blood pressure during CPT. Hyper-responders had a significantly lower baseline heart rate (64 ± 7 bpm), cardiac output (5.6 ± 0.9 L · min-1), and SαA (60 ± 37 U · mL-1) compared to hypo-responders (73 ± 9 bpm, 6.9 ± 1.3 L · min-1, 165 ± 122 U · mL-1). During the cold immersion, hyper-responders had significantly higher systolic blood pressure (150 ± 14 mmHg), diastolic blood pressure (91 ± 10 mmHg), mean arterial pressure (129 ± 17 mmHg), and systemic vascular resistance (1780 ± 640 dyn · s-1 · cm-5) than hypo-responders (130 ± 14 mmHg, 81 ± 10 mmHg, 110 ± 9 mmHg, 1290 ± 220 dyn · s-1 · cm-5). The change in systolic blood pressure correlated with baseline SαA (r = -0.455, P = 0.011) and baseline heart rate (r = -0.374, P = 0.042). Baseline characteristics influenced by sympathetic tone such as SαA, heart rate, and cardiac output are indicative of responses to CPT. Our data supports the use of baseline values to predict blood pressure response to acute cold exposure and indicates an intrinsic difference between CPT responder phenotypes.Youssef M, Ghassemi A, Carvajal Gonczi CM, Kugathasan TA, Kilgour RD, Darlington PJ. Low baseline sympathetic tone correlates to a greater blood pressure change in the cold pressor test. Aerosp Med Hum Perform. 2018; 89(6):503-509.

Therapeutic Strategies for Sleep Apnea in Hypertension and Heart Failure

PubMed Central

Noda, Akiko; Miyata, Seiko; Yasuda, Yoshinari

2013-01-01

Sleep-disordered breathing (SDB) causes hypoxemia, negative intrathoracic pressure, and frequent arousal, contributing to increased cardiovascular disease mortality and morbidity. Obstructive sleep apnea syndrome (OSAS) is linked to hypertension, ischemic heart disease, and cardiac arrhythmias. Successful continuous positive airway pressure (CPAP) treatment has a beneficial effect on hypertension and improves the survival rate of patients with cardiovascular disease. Thus, long-term compliance with CPAP treatment may result in substantial blood pressure reduction in patients with resistant hypertension suffering from OSAS. Central sleep apnea and Cheyne-Stokes respiration occur in 30–50% of patients with heart failure (HF). Intermittent hypoxemia, nocturnal surges in sympathetic activity, and increased left ventricular preload and afterload due to negative intrathoracic pressure all lead to impaired cardiac function and poor life prognosis. SDB-related HF has been considered the potential therapeutic target. CPAP, nocturnal O2 therapy, and adaptive servoventilation minimize the effects of sleep apnea, thereby improving cardiac function, prognosis, and quality of life. Early diagnosis and treatment of SDB will yield better therapeutic outcomes for hypertension and HF. PMID:23509623

School burnout: increased sympathetic vasomotor tone and attenuated ambulatory diurnal blood pressure variability in young adult women.

PubMed

May, Ross W; Sanchez-Gonzalez, Marcos A; Fincham, Frank D

2015-01-01

Two studies examined autonomic and cardiovascular functioning that may link school burnout to cardiovascular risk factors in young healthy adult females. Study 1 (N = 136) investigated whether school burnout was related to resting values of blood pressure (BP) and blood pressure variability (BPV) through laboratory beat-to-beat BP assessment. Study 2 (N = 94) examined the link between school burnout and diurnal BPV through ambulatory BP monitoring. Controlling for anxiety and depressive symptomatology, school burnout demonstrated strong positive relationships with indices of cardiac sympathovagal tone, sympathetic vasomotor tone, inefficient myocardial oxygen consumption, increased 24-h ambulatory heart rate and BP, blunted BP diurnal variability, and increased arterial stiffness. These studies establish cardiovascular biomarkers of school burnout and suggest that even in a seemingly healthy sample school burnout may predispose females to increased cardiovascular risk. Several future lines of research are outlined.

Usefulness of severe cardiac sympathetic dysfunction to predict the occurrence of rapid atrial fibrillation in patients with Wolff-Parkinson-White syndrome.

PubMed

Akutsu, Yasushi; Kaneko, Kyouichi; Kodama, Yusuke; Li, Hui-Ling; Asano, Taku; Suyama, Jumpei; Tanno, Kaoru; Namiki, Atsuo; Shinozuka, Akira; Gokan, Takehiko; Kobayashi, Youichi

2013-09-01

Atrial fibrillation (AF) can be a potentially life-threatening arrhythmia when it conducts rapidly through the accessory pathway, which was not predicted by the noninvasive method. We evaluated the cardiac sympathetic activity for predicting the occurrence of AF in patients with Wolff-Parkinson-White (WPW) syndrome. Iodine-123 metaiodobenzylguanidine scintigraphy was performed under stable sinus rhythm conditions at rest <1 week before an electrophysiologic study (EPS) to assess the sympathetic activity using the heart/mediastinum (H/M) ratio in 45 consecutive patients with WPW who had a history of supraventricular tachycardia (mean ± SD, age: 47 ± 17 years, 42.2% women). The study also included 15 normal healthy volunteers (56 ± 17 years, 40% women). The H/M ratio was lower in patients with WPW syndrome than in the normal control group, and in the 15 patients with AF induced during EPS than in the 30 patients without AF (p <0.0001). The sensitivity of H/M ratio ≤2.8 for predicting the AF induced during EPS was 75% in 12 of 16 patients, and the specificity was 89.7% in 26 of 29 patients. The H/M ratio was positively correlated with anterograde effective refractory period (r = 0.514, p <0.0001). The sensitivity of H/M ratio ≤2.75 for predicting the AF with a short anterograde effective refractory period (≤250 ms) was 91.7% in 11 of 12 patients, and the specificity was 90.9% in 30 of 33 patients. In conclusion, the severe cardiac sympathetic dysfunction was associated with the occurrence of AF, particularly in those with rapid AF and in patients with WPW syndrome. Copyright © 2013 Elsevier Inc. All rights reserved.

Area at risk can be assessed by iodine-123-meta-iodobenzylguanidine single-photon emission computed tomography after myocardial infarction: a prospective study.

PubMed

Hedon, Christophe; Huet, Fabien; Ben Bouallegue, Fayçal; Vernhet, Hélène; Macia, Jean-Christophe; Cung, Thien-Tri; Leclercq, Florence; Cade, Stéphane; Cransac, Frédéric; Lattuca, Benoit; Vandenberghe, D'Arcy; Bourdon, Aurélie; Benkiran, Meriem; Vauchot, Fabien; Gervasoni, Richard; D'estanque, Emmanuel; Mariano-Goulart, Denis; Roubille, François

2018-02-01

Myocardial salvage is an important surrogate endpoint to estimate the impact of treatments in patients with ST-segment elevation myocardial infarction (STEMI). The aim of this study was to evaluate the correlation between cardiac sympathetic denervation area assessed by single-photon emission computed tomography (SPECT) using iodine-123-meta-iodobenzylguanidine (I-MIBG) and myocardial area at risk (AAR) assessed by cardiac magnetic resonance (CMR) (gold standard). A total of 35 postprimary reperfusion STEMI patients were enrolled prospectively to undergo SPECT using I-MIBG (evaluates cardiac sympathetic denervation) and thallium-201 (evaluates myocardial necrosis), and to undergo CMR imaging using T2-weighted spin-echo turbo inversion recovery for AAR and postgadolinium T1-weighted phase sensitive inversion recovery for scar assessment. I-MIBG imaging showed a wider denervated area (51.1±16.0% of left ventricular area) in comparison with the necrosis area on thallium-201 imaging (16.1±14.4% of left ventricular area, P<0.0001). CMR and SPECT provided similar evaluation of the transmural necrosis (P=0.10) with a good correlation (R=0.86, P<0.0001). AAR on CMR was not different compared with the denervated area (P=0.23) and was adequately correlated (R=0.56, P=0.0002). Myocardial salvage evaluated by SPECT imaging (mismatch denervated but viable myocardium) was significantly higher than by CMR (P=0.02). In patients with STEMI, I-MIBG SPECT, assessing cardiac sympathetic denervation may precisely evaluate the AAR, providing an alternative to CMR for AAR assessment.

Preserved cardiac autonomic dynamics during sleep in subjects with spinal cord injuries.

PubMed

Tobaldini, Eleonora; Proserpio, Paola; Sambusida, Katrina; Lanza, Andrea; Redaelli, Tiziana; Frigerio, Pamela; Fratticci, Lara; Rosa, Silvia; Casali, Karina R; Somers, Virend K; Nobili, Lino; Montano, Nicola

2015-06-01

Spinal cord injuries (SCI) are associated with altered cardiovascular autonomic control (CAC). Sleep is characterized by modifications of autonomic control across sleep stages; however, no data are available in SCI subjects on CAC during sleep. We aim to assess cardiac autonomic modulation during sleep in subjects with SCI. 27 participants with a neurological and radiological diagnosis of cervical (Cerv, n = 12, ie, tetraplegic) and thoracic SCI (Thor, n = 15, ie, paraplegic) and healthy subjects (Controls) were enrolled. Overnight polysomnographic (PSG) recordings were obtained in all participants. Electrocardiography and respiration were extracted from PSG, divided into sleep stages [wakefulness (W), non-REM sleep (NREM) and REM] for assessment of CAC, using symbolic analysis (SA) and corrected conditional entropy (CCE). SA identified indices of sympathetic and parasympathetic modulation and CCE evaluated the degree of complexity of the heart period time series. SA revealed a reduction of sympathetic and predominant parasympathetic control during NREM compared to W and REM in SCI patients, independent of the level of the lesion, similar to the Controls. In all three groups, complexity of autonomic regulation was higher in NREM compared to W and REM. In subjects with SCI, cardiac autonomic control changed across sleep stages, with a reduction of sympathetic and an increase of parasympathetic modulation during NREM compared to W and REM, and a parallel increase of complexity during NREM, which was similar to the Controls. Cardiac autonomic dynamics during sleep are maintained in SCI, independent of the level of the lesion. Copyright © 2014 Elsevier B.V. All rights reserved.

Central vs. peripheral neuraxial sympathetic control of porcine ventricular electrophysiology

PubMed Central

Yamakawa, Kentaro; Howard-Quijano, Kimberly; Zhou, Wei; Rajendran, Pradeep; Yagishita, Daigo; Vaseghi, Marmar; Ajijola, Olujimi A.; Armour, J. Andrew; Shivkumar, Kalyanam; Ardell, Jeffrey L.

2015-01-01

Sympathoexcitation is associated with ventricular arrhythmogenesis. The aim of this study was to determine the role of thoracic dorsal root afferent neural inputs to the spinal cord in modulating ventricular sympathetic control of normal heart electrophysiology. We hypothesize that dorsal root afferent input tonically modulates basal and evoked efferent sympathetic control of the heart. A 56-electrode sock placed on the epicardial ventricle in anesthetized Yorkshire pigs (n = 17) recorded electrophysiological function, as well as activation recovery interval (ARI) and dispersion in ARI, at baseline conditions and during stellate ganglion electrical stimulation. Measures were compared between intact states and sequential unilateral T1–T4 dorsal root transection (DRTx), ipsilateral ventral root transection (VRTx), and contralateral dorsal and ventral root transections (DVRTx). Left or right DRTx decreased global basal ARI [Lt.DRTx: 369 ± 12 to 319 ± 13 ms (P < 0.01) and Rt.DRTx: 388 ± 19 to 356 ± 15 ms (P < 0.01)]. Subsequent unilateral VRTx followed by contralateral DRx+VRTx induced no further change. In intact states, left and right stellate ganglion stimulation shortened ARIs (6 ± 2% vs. 17 ± 3%), while increasing dispersion (+139% vs. +88%). There was no difference in magnitude of ARI or dispersion change with stellate stimulation following spinal root transections. Interruption of thoracic spinal afferent signaling results in enhanced basal cardiac sympathoexcitability without diminishing the sympathetic response to stellate ganglion stimulation. This suggests spinal dorsal root transection releases spinal cord-mediated tonic inhibitory control of efferent sympathetic tone, while maintaining intrathoracic cardiocentric neural networks. PMID:26661096

Premature Ventricular Contraction Coupling Interval Variability Destabilizes Cardiac Neuronal and Electrophysiological Control: Insights From Simultaneous Cardioneural Mapping.

PubMed

Hamon, David; Rajendran, Pradeep S; Chui, Ray W; Ajijola, Olujimi A; Irie, Tadanobu; Talebi, Ramin; Salavatian, Siamak; Vaseghi, Marmar; Bradfield, Jason S; Armour, J Andrew; Ardell, Jeffrey L; Shivkumar, Kalyanam

2017-04-01

Variability in premature ventricular contraction (PVC) coupling interval (CI) increases the risk of cardiomyopathy and sudden death. The autonomic nervous system regulates cardiac electrical and mechanical indices, and its dysregulation plays an important role in cardiac disease pathogenesis. The impact of PVCs on the intrinsic cardiac nervous system, a neural network on the heart, remains unknown. The objective was to determine the effect of PVCs and CI on intrinsic cardiac nervous system function in generating cardiac neuronal and electric instability using a novel cardioneural mapping approach. In a porcine model (n=8), neuronal activity was recorded from a ventricular ganglion using a microelectrode array, and cardiac electrophysiological mapping was performed. Neurons were functionally classified based on their response to afferent and efferent cardiovascular stimuli, with neurons that responded to both defined as convergent (local reflex processors). Dynamic changes in neuronal activity were then evaluated in response to right ventricular outflow tract PVCs with fixed short, fixed long, and variable CI. PVC delivery elicited a greater neuronal response than all other stimuli ( P <0.001). Compared with fixed short and long CI, PVCs with variable CI had a greater impact on neuronal response ( P <0.05 versus short CI), particularly on convergent neurons ( P <0.05), as well as neurons receiving sympathetic ( P <0.05) and parasympathetic input ( P <0.05). The greatest cardiac electric instability was also observed after variable (short) CI PVCs. Variable CI PVCs affect critical populations of intrinsic cardiac nervous system neurons and alter cardiac repolarization. These changes may be critical for arrhythmogenesis and remodeling, leading to cardiomyopathy. © 2017 American Heart Association, Inc.

Ghrelin potentiates cardiac reactivity to stress by modulating sympathetic control and beta-adrenergic response.

PubMed

Camargo-Silva, Gabriel; Turones, Larissa Córdova; da Cruz, Kellen Rosa; Gomes, Karina Pereira; Mendonça, Michelle Mendanha; Nunes, Allancer; de Jesus, Itamar Guedes; Colugnati, Diego Basile; Pansani, Aline Priscila; Pobbe, Roger Luis Henschel; Santos, Robson; Fontes, Marco Antônio Peliky; Guatimosim, Silvia; de Castro, Carlos Henrique; Ianzer, Danielle; Ferreira, Reginaldo Nassar; Xavier, Carlos Henrique

2018-03-01

Prior evidence indicates that ghrelin is involved in the integration of cardiovascular functions and behavioral responses. Ghrelin actions are mediated by the growth hormone secretagogue receptor subtype 1a (GHS-R1a), which is expressed in peripheral tissues and central areas involved in the control of cardiovascular responses to stress. In the present study, we assessed the role of ghrelin - GHS-R1a axis in the cardiovascular reactivity to acute emotional stress in rats. Ghrelin potentiated the tachycardia evoked by restraint and air jet stresses, which was reverted by GHS-R1a blockade. Evaluation of the autonomic balance revealed that the sympathetic branch modulates the ghrelin-evoked positive chronotropy. In isolated hearts, the perfusion with ghrelin potentiated the contractile responses caused by stimulation of the beta-adrenergic receptor, without altering the amplitude of the responses evoked by acetylcholine. Experiments in isolated cardiomyocytes revealed that ghrelin amplified the increases in calcium transient changes evoked by isoproterenol. Taken together, our results indicate that the Ghrelin-GHS-R1a axis potentiates the magnitude of stress-evoked tachycardia by modulating the autonomic nervous system and peripheral mechanisms, strongly relying on the activation of cardiac calcium transient and beta-adrenergic receptors. Copyright © 2018 Elsevier Inc. All rights reserved.

Cardiovascular Control in Men and Women

NASA Astrophysics Data System (ADS)

Fu, Qi

Women, primarily young women, have a greater incidence of orthostatic intolerance than agematched men. This difference is especially dramatic in the Postural Orthostatic Tachycardia Syndrome (POTS, also called Chronic Orthostatic Intolerance, in which patients are unable to stand or remain upright for prolonged periods of time due to intolerable light headedness, weakness, and near-syncope). However, the mechanisms underlying this gender difference are still not completely understood. It is likely that certain gender-specific factors such as the normal menstrual cycle, differences in some hormonal levels which may affect the neurohumoral regulation of blood pressure, or physical characteristics such as a smaller and less "distensible" heart may influence orthostatic blood pressure control. The authors review what has been done on the effects of gender and the menstrual cycle on sympathetic neural control of hemodynamics during shortand long-term orthostasis in healthy young individuals and in female patients with POTS. In addition, the role of cardiac size and function, a non-neural mechanism, in gender differences in orthostatic tolerance is also reviewed. It is suggested that sympathetic neural control and vasoconstrictor responses during orthostasis are comparable between healthy men and women, and are enhanced but not impaired in POTS patients. There is a gender-specific difference in cardiac size even in the healthy population, while this difference is exaggerated in female patients with POTS.

Renal denervation improves cardiac function in rats with chronic heart failure: Effects on expression of β-adrenoceptors

PubMed Central

Zheng, Hong; Liu, Xuefei; Sharma, Neeru M.

2016-01-01

Chronic activation of the sympathetic drive contributes to cardiac remodeling and dysfunction during chronic heart failure (HF). The present study was undertaken to assess whether renal denervation (RDN) would abrogate the sympathoexcitation in HF and ameliorate the adrenergic dysfunction and cardiac damage. Ligation of the left coronary artery was used to induce HF in Sprague-Dawley rats. Four weeks after surgery, RDN was performed, 1 wk before the final measurements. At the end of the protocol, cardiac function was assessed by measuring ventricular hemodynamics. Rats with HF had an average infarct area >30% of the left ventricle and left ventricular end-diastolic pressure (LVEDP) >20 mmHg. β1- and β2-adrenoceptor proteins in the left ventricle were reduced by 37 and 49%, respectively, in the rats with HF. RDN lowered elevated levels of urinary excretion of norepinephrine and brain natriuretic peptide levels in the hearts of rats with HF. RDN also decreased LVEDP to 10 mmHg and improved basal dP/dt to within the normal range in rats with HF. RDN blunted loss of β1-adrenoceptor (by 47%) and β2-adrenoceptor (by 100%) protein expression and improved isoproterenol (0.5 μg/kg)-induced increase in +dP/dt (by 71%) and −dP/dt (by 62%) in rats with HF. RDN also attenuated the increase in collagen 1 expression in the left ventricles of rats with HF. These findings demonstrate that RDN initiated in chronic HF condition improves cardiac function mediated by adrenergic agonist and blunts β-adrenoceptor expression loss, providing mechanistic insights for RDN-induced improvements in cardiac function in the HF condition. PMID:27288440

Systemic Sympathoexcitation Was Associated with Paraventricular Hypothalamic Phosphorylation of Synaptic CaMKIIα and MAPK/ErK.

PubMed

Ogundele, Olalekan M; Rosa, Fernando A; Dharmakumar, Rohan; Lee, Charles C; Francis, Joseph

2017-01-01

Systemic administration of adrenergic agonist (Isoproterenol; ISOP) is known to facilitate cardiovascular changes associated with heart failure through an upregulation of cardiac toll-like receptor 4 (TLR4). Furthermore, previous studies have shown that cardiac tissue-specific deletion of TLR4 protects the heart against such damage. Since the autonomic regulation of systemic cardiovascular function originates from pre-autonomic sympathetic centers in the brain, it is unclear how a systemically driven sympathetic change may affect the pre-autonomic paraventricular hypothalamic nuclei (PVN) TLR4 expression. Here, we examined how change in PVN TLR4 was associated with alterations in the neurochemical cytoarchitecture of the PVN in systemic adrenergic activation. After 48 h of intraperitoneal 150 mg/kg ISOP treatment, there was a change in PVN CaMKIIα and MAPK/ErK expression, and an increase in TLR4 in expression. This was seen as an increase in p-MAPK/ErK, and a decrease in synaptic CaMKIIα expression in the PVN ( p < 0.01) of ISOP treated mice. Furthermore, there was an upregulation of vesicular glutamate transporter (VGLUT 2; p < 0.01) and a decreased expression of GABA in the PVN of Isoproterenol (ISOP) treated WT mice ( p < 0.01). However, after a PVN-specific knockdown of TLR4, the effect of systemic administration of ISOP was attenuated, as indicated by a decrease in p-MAPK/ErK ( p < 0.01) and upregulation of CaMKIIα ( p < 0.05). Additionally, loss of inhibitory function was averted while VGLUT2 expression decreased when compared with the ISOP treated wild type mice and the control. Taken together, the outcome of this study showed that systemic adrenergic activation may alter the expression, and phosphorylation of preautonomic MAPK/ErK and CaMKIIα downstream of TLR4. As such, by outlining the roles of these kinases in synaptic function, we have identified the significance of neural TLR4 in the progression, and attenuation of synaptic changes in the pre-autonomic sympathetic centers.

Evaluation of cardiac modulation in children in response to apnea/hypopnea using the Phone Oximeter(™).

PubMed

Dehkordi, Parastoo; Garde, Ainara; Karlen, Walter; Petersen, Christian L; Wensley, David; Dumont, Guy A; Mark Ansermino, J

2016-02-01

Individuals with sleep disordered breathing (SDB) can experience changes in automatic cardiac regulation as a result of frequent sleep fragmentation and disturbance in normal respiration and oxygenation that accompany most apnea/hypopnea events. In adults, these changes are reflected in enhanced sympathetic and reduced parasympathetic activity. In this study, we examined the autonomic cardiac regulation in children with and without SDB, through spectral and detrended fluctuation analysis (DFA) of pulse rate variability (PRV). PRV was measured from pulse-to-pulse intervals (PPIs) of the photoplethysmogram (PPG) recorded from 160 children using the Phone Oximeter(™) in the standard setting of overnight polysomnography. Spectral analysis of PRV showed the cardiac parasympathetic index (high frequency, HF) was lower (p < 0.01) and cardiac sympathetic indices (low frequency, LF and LF/HF ratio) were higher (p < 0.01) during apnea/hypopnea events for more than 95% of children with SDB. DFA showed the short- and long-range fluctuations of heart rate were more strongly correlated in children with SDB compared to children without SDB. These findings confirm that the analysis of the PPG recorded using the Phone Oximeter(™) could be the basis for a new screening tool for assessing PRV in non-clinical environment.

Regional heterogeneity in cardiac sympathetic innervation in acute myocardial infarction: relationship with myocardial oedema on magnetic resonance.

PubMed

Gimelli, Alessia; Masci, Pier Giorgio; Liga, Riccardo; Grigoratos, Chrysanthos; Pasanisi, Emilio Maria; Lombardi, Massimo; Marzullo, Paolo

2014-09-01

To assess the relationships between myocardial structure and function on cardiac magnetic resonance (CMR) imaging and sympathetic tone on (123)I-metaiodobenzylguanidine ((123)I-MIBG) scintigraphy early after myocardial infarction (MI). Ten patients underwent (123)I-MIBG and (99m)Tc-tetrofosmin rest cadmium zinc telluride scintigraphy 4 ± 1 days after MI. The segmental left ventricular (LV) relative radiotracer uptake of both (99m)Tc-tetrofosmin and early (123)I-MIBG was calculated. The day after scintigraphy, on CMR imaging, the extent of ischaemia-related oedema and of myocardial fibrosis (late gadolinium enhancement, LGE) was assessed. Accordingly, the extent of oedema and LGE was evaluated for each segment and segmental wall thickening determined. Based on LGE distribution, LV segments were categorized as "infarcted" (56 segments), "adjacent" (66 segments) or "remote" (48 segments). Infarcted segments showed a more depressed systolic wall thickening and greater extent of oedema than adjacent segments (p < 0.001) and remote segments (p < 0.001). Interestingly, while uptake of (99m)Tc-tetrofosmin was significantly depressed only in infarcted segments (p < 0.001 vs. both adjacent and remote segments), uptake of (123)I-MIBG was impaired not only in infarcted segments (p < 0.001 vs. remote) but also in adjacent segments (p = 0.024 vs. remote segments). At the regional level, after correction for (99m)Tc-tetrofosmin and LGE distribution, segmental (123)I-MIBG uptake (p < 0.001) remained an independent predictor of ischaemia-related oedema. After acute MI the regional impairment of sympathetic tone extends beyond the area of altered myocardial perfusion and is associated with myocardial oedema.

Autonomic responses to cold face stimulation in sickle cell disease: a time-varying model analysis.

PubMed

Chalacheva, Patjanaporn; Kato, Roberta M; Sangkatumvong, Suvimol; Detterich, Jon; Bush, Adam; Wood, John C; Meiselman, Herbert; Coates, Thomas D; Khoo, Michael C K

2015-07-14

Sickle cell disease (SCD) is characterized by sudden onset of painful vaso-occlusive crises (VOC), which occur on top of the underlying chronic blood disorder. The mechanisms that trigger VOC remain elusive, but recent work suggests that autonomic dysfunction may be an important predisposing factor. Heart-rate variability has been employed in previous studies, but the derived indices have provided only limited univariate information about autonomic cardiovascular control in SCD. To circumvent this limitation, a time-varying modeling approach was applied to investigate the functional mechanisms relating blood pressure (BP) and respiration to heart rate and peripheral vascular resistance in healthy controls, untreated SCD subjects and SCD subjects undergoing chronic transfusion therapy. Measurements of respiration, heart rate, continuous noninvasive BP and peripheral vascular resistance were made before, during and after the application of cold face stimulation (CFS), which perturbs both the parasympathetic and sympathetic nervous systems. Cardiac baroreflex sensitivity estimated from the model was found to be impaired in nontransfused SCD subjects, but partially restored in SCD subjects undergoing transfusion therapy. Respiratory-cardiac coupling gain was decreased in SCD and remained unchanged by chronic transfusion. These results are consistent with autonomic dysfunction in the form of impaired parasympathetic control and sympathetic overactivity. As well, CFS led to a significant reduction in vascular resistance baroreflex sensitivity in the nontransfused SCD subjects but not in the other groups. This blunting of the baroreflex control of peripheral vascular resistance during elevated sympathetic drive could be a potential factor contributing to the triggering of VOC in SCD. © 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

Dissociation of hemodynamic and electrocardiographic indexes of myocardial ischemia in pigs with hibernating myocardium and sudden cardiac death.

PubMed

Pizzuto, Matthew F; Suzuki, Gen; Banas, Michael D; Heavey, Brendan; Fallavollita, James A; Canty, John M

2013-06-15

Many survivors of sudden cardiac death (SCD) have normal global ventricular function and severe coronary artery disease but no evidence of symptomatic ischemia or infarction before the development of lethal ventricular arrhythmias, and the trigger for ventricular tachycardia (VT)/ventricular fibrillation (VF) remains unclear. We sought to identify the role of spontaneous ischemia and temporal hemodynamic factors preceding SCD using continuous telemetry of left ventricular (LV) pressure and the ECG for periods up to 5 mo in swine (n = 37) with hibernating myocardium who experience spontaneous VT/VF in the absence of heart failure or infarction. Hemodynamics and ST deviation at the time of VT/VF were compared with survivors with hibernating myocardium as well as sham controls. All episodes of VT/VF occurred during sympathetic activation and were initiated by single premature ventricular contractions, and the VT degenerated into VF in ∼ 30 s. ECG evidence of ischemia was infrequent and no different from those that survived. Baseline hemodynamics were no different among groups, but LV end-diastolic pressure during sympathetic activation was higher at the time of SCD (37 ± 4 vs. 26 ± 4 mmHg, P < 0.05) and the ECG demonstrated QT shortening (155 ± 4 vs. 173 ± 5 ms, P < 0.05). The week before SCD, both parameters were no different from survivors. These data indicate that there are no differences in the degree of sympathetic activation or hemodynamic stress when VT/VF develops in swine with hibernating myocardium. The transiently elevated LV end-diastolic pressure and QT shortening preceding VT/VF raises the possibility that electrocardiographically silent subendocardial ischemia and/or mechanoelectrical feedback serve as a trigger for the development of SCD in chronic ischemic heart disease.

Heterogeneity of prejunctional NPY receptor-mediated inhibition of cardiac neurotransmission

PubMed Central

Serone, Adrian P; Wright, Christine E; Angus, James A

1999-01-01

Neuropeptide Y (NPY) has been proposed as the candidate inhibitory peptide mediating interactions between sympathetic and vagal neurotransmission in several species, including man. Here, we have defined the NPY receptors involved in modulation of cardiac autonomic neurotransmission using receptor-selective agonists and antagonists in the rabbit and guinea-pig isolated right atria.In isolated atrial preparations, sympathetically-mediated tachycardia (ST; with atropine 1 μM) or vagally-mediated bradycardia (VB; with propranolol 0.1–1 μM) in response to electrical field stimulation (EFS, 1–4 pulses) were tested 0–30 min after incubation with single concentrations of vehicle, NPY (0.01–10 μM), the Y2 receptor agonist N-Acetyl-[Leu28,31]NPY(24–36) (termed N-A[L]NPY(24–36)) or the Y1 receptor agonist [Leu31,Pro34]NPY (LP). The effect of NPY on the concentration-chronotropic response curves to isoprenaline and bethanechol were also assessed.Guinea-pig atria: NPY and N-A[L]NPY(24–36) caused concentration-dependent inhibition of VB and ST to EFS. Both peptides caused maximal inhibition of VB and ST within 10 min incubation and this remained constant. LP caused a concentration-dependent, transient inhibition of ST which was antagonized by the Y1-receptor antagonist GR231118 (0.3 μM), with apparent competitive kinetics. Rabbit atria: NPY (1 or 10 μM) had no effect on VB at any time point, but both NPY and LP caused a transient (∼10 min) inhibition of sympathetic tachycardia. This inhibition could be prevented by 0.3 μM GR231118. N-A[L]NPY(24–36) had no effect on ST. NPY had no effect on the response to β-adrenoceptor stimulation by isoprenaline nor muscarinic-receptor stimulation by bethanechol in either species.Thus, in the guinea-pig, NPY causes a stable inhibition of both VB and ST to EFS via Y2 receptors and transient inhibition of ST via Y1 receptors. In contrast in the rabbit, NPY has no effect on the cardiac vagus and prejunctional inhibition of ST is transient and mediated by a Y1-like receptor (rather than Y2). Therefore it would be surprising if NPY plays a functional role in modulation of cardiac neurotransmission in the rabbit. PMID:10369461

[Effect of substance P on cardiac autonomic nervous function in rats].

PubMed

Deng, Lijun; Li, Jing; Yan, Fuping; Lu, Jie

2009-12-01

Forty SD rats were divided into 5 groups: control group, SP groups (5 microg/kg,10 microg/kg, 20 microg/kg) and spantide II plus SP group. An analysis of heart rate variability (HRV) was used to detect the changes of HRV parameters before and after intravenous injection of SP in order to investigate the effect of substance P on cardiac autonomic nervous function and the corresponding mechanism. (1) There were significant differences in most HRV parameters for the three different doses of SP. Mean heart period (MHP), absolute power of ultra-low frequency and high frequency band (APU, APH), total power (TPV) and ratio of power in ultra-low to high frequency band (RUH) increased, while mean heart rate (MHR) and chaos intensity (HCC) decreased during the 30 minutes. Each peak amplitude of HRV parameters went higher and showed up ahead of the upward doses of SP. (2) Significant change was seen in each of the parameters between spantide II plus SP group and high-dose SP group. These data idicate that, after intravenous injection of different doses of SP, both cardiac sympathetic nervous system activity and parasympathetic nervous system activity increase, and the function of cardiac autonomic nervous becomes instable and unbalanced. The effect of SP may be dose dependent, and it is possibly mediated by neurokinin-1(NK-1) receptor.

Experimental myocardial infarction

PubMed Central

Kumar, Raj; Joison, Julio; Gilmour, David P.; Molokhia, Farouk A.; Pegg, C. A. S.; Hood, William B.

1971-01-01

The hemodynamic effects of tachycardia induced by atrial pacing were investigated in left ventricular failure of acute and healing experimental myocardial infarction in 20 intact, conscious dogs. Myocardial infarction was produced by gradual inflation of a balloon cuff device implanted around the left anterior descending coronary artery 10-15 days prior to the study. 1 hr after acute myocardial infarction, atrial pacing at a rate of 180 beats/min decreased left ventricular end-diastolic pressure from 19 to 8 mm Hg and left atrial pressure from 17 to 12 mm Hg, without change in cardiac output. In the healing phase of myocardial infarction 1 wk later, atrial pacing decreased left ventricular end-diastolic pressure from 17 to 9 mm Hg and increased the cardiac output by 37%. This was accompanied by evidence of peripheral vasodilation. In two dogs with healing anterior wall myocardial infarction, left ventricular failure was enhanced by partial occlusion of the circumflex coronary artery. Both the dogs developed pulmonary edema. Pacing improved left ventricular performance and relieved pulmonary edema in both animals. In six animals propranolol was given after acute infarction, and left ventricular function deteriorated further. However the pacing-induced augmentation of cardiac function was unaltered and, hence, is not mediated by sympathetics. The results show that the spontaneous heart rate in left ventricular failure of experimental canine myocardial infarction may be less than optimal and that maximal cardiac function may be achieved at higher heart rates. Images PMID:4395910

Hemodynamic and neurochemical determinates of renal function in chronic heart failure.

PubMed

Gilbert, Cameron; Cherney, David Z I; Parker, Andrea B; Mak, Susanna; Floras, John S; Al-Hesayen, Abdul; Parker, John D

2016-01-15

Abnormal renal function is common in acute and chronic congestive heart failure (CHF) and is related to the severity of congestion. However, treatment of congestion often leads to worsening renal function. Our objective was to explore basal determinants of renal function and their response to hemodynamic interventions. Thirty-seven patients without CHF and 59 patients with chronic CHF (ejection fraction; 23 ± 8%) underwent right heart catheterization, measurements of glomerular filtration rate (GFR; inulin) and renal plasma flow (RPF; para-aminohippurate), and radiotracer estimates of renal sympathetic activity. A subset (26 without, 36 with CHF) underwent acute pharmacological intervention with dobutamine or nitroprusside. We explored the relationship between baseline and drug-induced hemodynamic changes and changes in renal function. In CHF, there was an inverse relationship among right atrial mean pressure (RAM) pressure, RPF, and GFR. By contrast, mean arterial pressure (MAP), cardiac index (CI), and measures of renal sympathetic activity were not significant predictors. In those with CHF there was also an inverse relationship among the drug-induced changes in RAM as well as pulmonary artery mean pressure and the change in GFR. Changes in MAP and CI did not predict the change in GFR in those with CHF. Baseline values and changes in RAM pressure did not correlate with GFR in those without CHF. In the CHF group there was a positive correlation between RAM pressure and renal sympathetic activity. There was also an inverse relationship among RAM pressure, GFR, and RPF in patients with chronic CHF. The observation that acute reductions in RAM pressure is associated with an increase in GFR in patients with CHF has important clinical implications. Copyright © 2016 the American Physiological Society.

2-Year Natural Decline of Cardiac Sympathetic Innervation in Idiopathic Parkinson Disease Studied with 11C-Hydroxyephedrine PET.

PubMed

Wong, Ka Kit; Raffel, David M; Bohnen, Nicolaas I; Altinok, Gulcin; Gilman, Sid; Frey, Kirk A

2017-02-01

The objective of this study was to detect regional patterns of cardiac sympathetic denervation in idiopathic Parkinson disease (IPD) using 11 C-hydroxyephedrine ( 11 C-HED) PET and determine the denervation rate over 2 y. We obtained 62 cardiac 11 C-HED PET scans in 39 patients (30 men and 9 women; mean age ± SD, 61.9 ± 5.9 y), including 23 patients with follow-up scans at 2 y. We derived 11 C-HED retention indices (RIs; mL of blood/min/mL of tissue) reflecting nerve density and integrity for 480 left ventricular (LV) sectors. We compared IPD patients with 33 healthy controls using z score analysis; RI values ≤ 2.5 SDs were considered abnormal. We expressed global and regional LV denervation as the percentage extent of z score severity and severity-extent product (SEP) on 9-segment bullseye maps and decline in cardiac sympathetic innervation as the 2-y difference in SEP (diff-SEP). Baseline 11 C-HED PET in the 39 IPD patients revealed an RI mean of 0.052 ± 0.022 mL of blood/min/mL of tissue. In comparison with data from normal controls, 12 patients had normal 11 C-HED PET, 5 showed mild denervation (percentage extent < 30%), and 22 had moderate to severe denervation (percentage extent > 30%, z score ≤ 2.5 SD). In the 23 paired PET scans, worsening cardiac denervation (global diff-SEP > 9) occurred in 14 of 23 (60.9%) patients over 2 y, including percentage LV abnormality (59% increasing to 66%), z-severity (-2.4 down to -2.5), and SEP (-195 to -227) (P = 0.0062). We found a mean annual decline of 4.6% ± 5.6 (maximum, 13%) in 11 C-HED retention from a baseline global RI mean of 0.0481 ± 0.0218 to 0.0432 ± 0.0220 (P = 0.0009). At baseline, 5 patients with normal uptake had no interval change; 3 with mild denervation developed interval decline in lateral and inferior segments (diff-SEP -82 to -99) compared with anterior and septal segments (-65 to -79), whereas the reverse pattern occurred in 15 patients with severe baseline denervation. Progressive decline in cardiac sympathetic neural integrity in IPD patients occurs at a modest rate over 2 y on 11 C-HED scans with marked heterogeneity and a regional pattern of involvement and decline. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

Influence of antipsychotic agents on heart rate variability in male WKY rats: implications for cardiovascular safety.

PubMed

Wang, Ying-Chieh; Chen, Chun-Yu; Kuo, Terry B J; Lai, Ching-Jung; Yang, Cheryl C H

2012-06-01

Sudden cardiac death is higher among schizophrenic patients and is associated with parasympathetic hypoactivity. Antipsychotic agents are highly suspected to be a precipitating factor. Thus, we aimed to test if the antipsychotics haloperidol, risperidone and clozapine affect cardiac autonomic function, excluding the confounding effect of altered sleep structure by the drugs. In this study, haloperidol, risperidone and clozapine were given separately by intraperitoneal injection to male Wistar-Kyoto rats for 5 days. Electroencephalogram (EEG), electromyogram (EMG) and electrocardiographic signals were recorded at baseline and 5 days after drug treatments. Sleep scoring was based on EEG and EMG signals. Cardiac autonomic function was assessed using heart rate variability analysis. Clozapine increased heart rate and suppressed cardiac sympathetic and parasympathetic activity. Cardiac acceleration was more severe during sleep. Haloperidol tended to decrease heart rate while risperidone mildly increased heart rate; however, their effects were less obvious than those of clozapine. There was a significant drug-by-stage interaction on several heart rate variability measures. Taking this evidence as a whole, we conclude that haloperidol has a better level of cardiovascular safety than either risperidone or clozapine. Application of this approach to other psychotropic agents in the future will be a useful and helpful way to evaluate the cardiovascular safety of the various psychotropic medications that are in clinical use. Copyright © 2012 S. Karger AG, Basel.

Role of Autophagy in Metabolic Syndrome-Associated Heart Disease

PubMed Central

Ren, Sidney Y.; Xu, Xihui

2014-01-01

Metabolic syndrome (MetS) is a constellation of multiple metabolic risk factors including abdominal obesity, glucose intolerance, insulin resistance, dyslipidemia and hypertension. Over the past decades, the prevalence of metabolic syndrome has increased dramatically, imposing a devastating, pandemic health threat. More importantly, individuals with metabolic syndrome are at an increased risk of diabetes mellitus and overall cardiovascular diseases. One of the common comorbidities of metabolic syndrome is heart anomalies leading to the loss of cardiomyocytes, cardiac dysfunction and ultimately heart failure. Up-to-date, a plethora cell signaling pathways have been postulated for the pathogenesis of cardiac complications in obesity including lipotoxicity, inflammation, oxidative stress, apoptosis and sympathetic overactivation although the precise mechanism of action underscoring obesity-associated heart dysfunction remains elusive. Recent evidence has indicated a potential role of protein quality control in components of metabolic syndrome. Within the protein quality control system, the autophagy-lysosome pathway is an evolutionarily conserved pathway responsible for bulk degradation of large intracellular organelles and protein aggregates. Autophagy has been demonstrated to play an indispensible role in the maintenance of cardiac geometry and function under both physiological and pathological conditions. Accumulating studies have demonstrated that autophagy plays a pivotal role in the etiology of cardiac anomalies under obesity and metabolic syndrome. In this mini review, we will discuss on how autophagy is involved in the regulation of cardiac function in obesity and metabolic syndrome. PMID:24810277

The sympathetic mechanism in the isolated pulmonary artery of the rabbit

PubMed Central

Bevan, J. A.; Su, C.

1964-01-01

The nature of postganglionic sympathetic nervous transmission to vascular muscle in vitro was studied using the recurrent cardiac nerve-pulmonary artery preparation of the rabbit. Experiments, similar to those which in other tissues have provided evidence to support a role for acetylcholine at the sympathetic postganglionic nerve-effector cell junction, were carried out. The contractile response of the isolated artery to acetylcholine was blocked completely by atropine. High concentrations of acetylcholine and of hemicholinium had no effect on the contractile response to sympathetic nerve stimulation. Physostigmine, atropine and hemicholinium were without influence on the relationship between nerve stimulus frequency and response. Yohimbine, bretylium and reserpine blocked completely the response to nerve stimulation but did not affect that to applied acetylcholine. These results support the view that transmission in this preparation at the sympathetic postganglionic nerve-effector cell junction is mediated by an adrenaline-like transmitter and provide no evidence for the view that acetylcholne is involved at this site. PMID:14126048

Autonomic contribution to the blood pressure and heart rate variability changes in early experimental hyperthyroidism.

PubMed

Safa-Tisseront, V; Ponchon, P; Laude, D; Elghozi, J L

1998-12-01

To study the interaction between autonomic nervous activity and thyroid hormones in the control of heart rate (HR) and blood pressure (BP). Thyrotoxicosis was produced by injections of L-thyroxine (0.5 mg/kg/day for five days). Blockers were atropine (0.5 mg/kg), atenolol (1 mg/kg) or prazosin (1 mg/kg). Eight animals were studied in each group. Spectral analyses was performed using continuous BP time series obtained in conscious rats. Thyroxine treatment was sufficient to induce a significant degree of tachycardia (423+/-6 vs 353+/-4 bpm, P < 0.001, unpaired Student's t test), systolic BP elevation (142+/-3 vs 127+/-2 mmHg, P < 0.001) and cardiac hypertrophy (1.165+/-0.017 vs 1.006+/-0.012 g, P < 0.001). The intrinsic HR was markedly increased after treatment with thyroxine (497+/-16 vs 373+/-10 bpm, P < 0.05). Vagal tone was positively linearly related to intrinsic HR (r = 0.84, P< 0.01). Atenolol neither modified HR nor BP variability in rats with hyperthyroidism. The thyrotoxicosis was associated with a reduction of the 0.4 Hz component of BP variability (modulus 1.10+/-0.07 vs 1.41+/-0.06 mmHg, P < 0.01). Prazosin was without effect on this 0.4 Hz component in hyperthyroid animals. These data show a functional diminution of the vascular and cardiac sympathetic tone in early experimental hyperthyroidism. The marked rise in the intrinsic HR could be the main determinant of tachycardia. The BP elevation may reflexly induce vagal activation and sympathetic (vascular and cardiac) inhibition.

Mechanisms of right heart disease in pulmonary hypertension (2017 Grover Conference Series).

PubMed

Asosingh, Kewal; Erzurum, Serpil

2018-01-01

Current dogma is that pathological hypertrophy of the right ventricle is a direct consequence of pulmonary vascular remodeling. However, progression of right ventricle dysfunction is not always lung-dependent. Increased afterload caused by pulmonary vascular remodeling initiates the right ventricle hypertrophy, but determinants leading to adaptive or maladaptive hypertrophy and failure remain unknown. Ischemia in a hypertrophic right ventricle may directly contribute to right heart failure. Rapidly enlarging cardiomyocytes switch from aerobic to anaerobic energy generation resulting in cell growth under relatively hypoxic conditions. Cardiac muscle reacts to an increased afterload by over-activation of the sympathetic system and uncoupling and downregulation of β-adrenergic receptors. Recent studies suggest that β blocker therapy in PH is safe, well tolerated, and preserves right ventricle function and cardiac output by reducing right ventricular glycolysis. Fibrosis, an evolutionary conserved process in host defense and wound healing, is dysregulated in maladaptive cardiac tissue contributing directly to right ventricle failure. Despite several mechanisms having been suggested in right heart disease, the causes of maladaptive cardiac remodeling remain unknown and require further research.

Congestive renal failure: the pathophysiology and treatment of renal venous hypertension.

PubMed

Ross, Edward A

2012-12-01

Longstanding experimental evidence supports the role of renal venous hypertension in causing kidney dysfunction and "congestive renal failure." A focus has been heart failure, in which the cardiorenal syndrome may partly be due to high venous pressure, rather than traditional mechanisms involving low cardiac output. Analogous diseases are intra-abdominal hypertension and renal vein thrombosis. Proposed pathophysiologic mechanisms include reduced transglomerular pressure, elevated renal interstitial pressure, myogenic and neural reflexes, baroreceptor stimulation, activation of sympathetic nervous and renin angiotensin aldosterone systems, and enhanced proinflammatory pathways. Most clinical trials have addressed the underlying condition rather than venous hypertension per se. Interpreting the effects of therapeutic interventions on renal venous congestion are therefore problematic because of such confounders as changes in left ventricular function, cardiac output, and blood pressure. Nevertheless, there is preliminary evidence from small studies of intense medical therapy or extracorporeal ultrafiltration for heart failure that there can be changes to central venous pressure that correlate inversely with renal function, independently from the cardiac index. Larger more rigorous trials are needed to definitively establish under what circumstances conventional pharmacologic or ultrafiltration goals might best be directed toward central venous pressures rather than left ventricular or cardiac output parameters. Copyright © 2012 Elsevier Inc. All rights reserved.

Cardiac iodine-123-metaiodobenzylguanidine scintigraphy may be useful to identify pathologic from physiologic sinus bradycardia.

PubMed

Sunaga, Akihiro; Masuda, Masaharu; Fujita, Masashi; Iida, Osamu; Kanda, Takashi; Matsuda, Yasuhiro; Morozumi, Takakazu; Mano, Toshiaki; Uematsu, Masaaki

2017-06-01

Sinus bradycardia includes pathologic sick sinus syndrome (SSS) and physiologic bradycardia such as athletes' heart. Pacemaker implantation is indicated for patients with symptomatic SSS; however, the indication remains difficult to determine in those with mild and/or unspecific symptoms. The sympathetic tone is increased in response to reduced cardiac output in SSS, whereas excessive vagal tone has been seen in physiological bradycardia. We sought to determine if cardiac iodine-123-metaiodobenzylguanidine scintigraphy ( 123 I-MIBG) was useful in differentiating pathologic from physiologic sinus bradycardia. Twenty consecutive patients presenting with continuous sinus bradycardia (heart rate of <50 beats/min) in our outpatient clinic (male, eight patients; age, 70 ± 12 years old) were enrolled. The indication for a pacemaker implantation was determined by an experienced electrophysiologist in compliance with the international guidelines. The sympathetic nervous tone was assessed by cardiac 123 I-MIBG. Eight patients (40%) were clinically diagnosed as SSS (type I) including four suffering from obvious symptoms (syncope or dizziness) and four suffering from mild symptoms (fatigue), and had an indication for a pacemaker implantation. The patients with SSS indicated for a pacemaker implantation had a lower early heart-to-mediastinum ratio (2.0 ± 0.6 vs 2.5 ± 0.2, P = 0.043), lower delayed heart to mediastinum ratio (2.0 ± 0.8 vs 2.8 ± 0.3, P = 0.026), and higher washout rate (34 ± 6.0 vs 26 ± 6.0, P = 0.008) than those without. Excessive sympathetic tone detected by 123 I-MIBG may serve as an adjunct to determine the indication for a pacemaker implantation in sinus bradycardia. © 2017 Wiley Periodicals, Inc.

Further analysis of the inhibition by agmatine on the cardiac sympathetic outflow: Role of the α2-adrenoceptor subtypes.

PubMed

Cobos-Puc, Luis; Aguayo-Morales, Hilda; Ventura-Sobrevilla, Janeth; Luque-Contreras, Diana; Chin-Chan, Miguel

2017-06-15

This study has investigated the role of the α 2 -adrenoceptor subtypes involved in the inhibition of the cardiac sympathetic outflow induced by intravenous (i.v) infusions of agmatine. Therefore, we analysed the effect of an i.v. bolus injections of the selective antagonists BRL 44408 (300μg/kg; α 2A ), imiloxan (3000μg/kg; α 2B ), and JP-1302 (300μg/kg; α 2C ) given separately, and their combinations: BRL 44408 plus Imiloxan, JP 1302 plus imiloxan, BRL 44408 plus JP-1302, BRL 44408 plus imiloxan plus JP-1302 on the cardiac sympatho-inhibition of agmatine. Also, the effect of the combination BRL 44408 plus JP-1302 plus AGN 192403 (3000μg/kg; I 1 antagonist) was evaluated. In this way, i.v. infusions of 1000μg/kg min of agmatine, but not 300, inhibited the tachycardic response induced by electrical stimulation. Furthermore, the antagonists used or their combinations had no effect on the electrically-induced tachycardic response. On the other hand, the inhibitory response of agmatine was: (1) partially antagonized by BRL 44408 or JP-1302 given separately, a similar response was observed when we administered their combination with imiloxan, but not by imiloxan alone, (2) antagonized in greater magnitude by the combination BRL 44408 plus JP-1302 or the combination BRL 44408 plus imiloxan plus JP-1302, and (3) abolished by the combination BRL 44408 plus JP-1302 plus AGN 192403. Taken together, these results demonstrate that the α 2A - and α 2C -adrenoceptor subtypes and I 1 -imidazoline receptors are involved in the inhibition of the cardiac sympathetic outflow induced by agmatine. Copyright © 2017 Elsevier B.V. All rights reserved.

Central exogenous nitric oxide decreases cardiac sympathetic drive and improves baroreflex control of heart rate in ovine heart failure.

PubMed

Ramchandra, Rohit; Hood, Sally G; May, Clive N

2014-08-01

Heart failure (HF) is associated with increased cardiac and renal sympathetic drive, which are both independent predictors of poor prognosis. A candidate mechanism for the centrally mediated sympathoexcitation in HF is reduced synthesis of the inhibitory neuromodulator nitric oxide (NO), resulting from downregulation of neuronal NO synthase (nNOS). Therefore, we investigated the effects of increasing the levels of NO in the brain, or selectively in the paraventricular nucleus of the hypothalamus (PVN), on cardiac sympathetic nerve activity (CSNA) and baroreflex control of CSNA and heart rate in ovine pacing-induced HF. The resting level of CSNA was significantly higher in the HF than in the normal group, but the resting level of RSNA was unchanged. Intracerebroventricular infusion of the NO donor sodium nitroprusside (SNP; 500 μg · ml(-1)· h(-1)) in conscious normal sheep and sheep in HF inhibited CSNA and restored baroreflex control of heart rate, but there was no change in RSNA. Microinjection of SNP into the PVN did not cause a similar cardiac sympathoinhibition in either group, although the number of nNOS-positive cells was decreased in the PVN of sheep in HF. Reduction of endogenous NO with intracerebroventricular infusion of N(ω)-nitro-l-arginine methyl ester decreased CSNA in normal but not in HF sheep and caused no change in RSNA in either group. These findings indicate that endogenous NO in the brain provides tonic excitatory drive to increase resting CSNA in the normal state, but not in HF. In contrast, exogenously administered NO inhibited CSNA in both the normal and HF groups via an action on sites other than the PVN. Copyright © 2014 the American Physiological Society.

Endogenous angiotensin affects responses to stimulation of baroreceptor afferent nerves.

PubMed

DiBona, Gerald F; Jones, Susan Y

2003-08-01

To study effects of endogenous angiotensin II on responses to standardized stimulation of afferent neural input into the central portion of the arterial and cardiac baroreflexes. Different dietary sodium intakes were used to physiologically alter endogenous angiotensin II activity. Candesartan, an angiotensin II type 1 receptor antagonist, was used to assess dependency of observed effects on angiotensin II stimulation of angiotensin II type 1 receptors. Electrical stimulation of arterial and cardiac baroreflex afferent nerves was used to provide a standardized input to the central portion of the arterial and cardiac baroreflexes. In anesthetized rats in balance on low, normal and high dietary sodium intake, arterial pressure, heart rate and renal sympathetic nerve activity responses to electrical stimulation of vagus and aortic depressor nerves were determined. Compared with plasma renin activity values in normal dietary sodium intake rats, those from low dietary sodium intake rats were higher and those from high dietary sodium intake rats were lower. During vagus nerve stimulation, the heart rate, arterial pressure and renal sympathetic nerve activity responses were similar in all three dietary sodium intake groups. During aortic depressor nerve stimulation, the heart rate and arterial pressure responses were similar in all three dietary sodium intake groups. However, the renal sympathetic nerve activity response was significantly greater in the low sodium group than in the normal and high sodium group at 4, 8 and 16 Hz. Candesartan administered to low dietary sodium intake rats had no effect on the heart rate and arterial pressure responses to either vagus or aortic depressor nerve stimulation but increased the magnitude of the renal sympathoinhibitory responses. Increased endogenous angiotensin II in rats on a low dietary sodium intake attenuates the renal sympathoinhibitory response to activation of the cardiac and sinoaortic baroreflexes by standardized vagus and aortic depressor nerve stimulation, respectively.

Thoracoscopic sympathectomy increases efferent cardiac vagal activity and baroreceptor sensitivity.

PubMed

Bygstad, Elisabeth; Terkelsen, Astrid J; Pilegaard, Hans K; Hansen, John; Mølgaard, Henning; Hjortdal, Vibeke E

2013-09-01

Thoracoscopic sympathectomy at levels T2 or T2-T3 is a treatment for focal hyperhidrosis and facial blushing. These levels of the sympathetic trunk innervate the heart, and consequently, the procedure is reported to change the heart rate variability due to changes in efferent cardiac autonomic activity. Our objective was to investigate the effects of thoracoscopic sympathectomy on global autonomic control, including baroreceptor sensitivity. Eight patients (6 F, median age 28 years [range 20-58 years]) were exposed to the tilt-table test and cardiopulmonary exercise test before, and 3 months after, thoracoscopic sympathectomy. Eight healthy age-, gender- and BMI-matched controls were used as controls and underwent the same tests once. During tilt-table testing electrocardiogram, blood pressure, impedance cardiography and respiration were measured continuously, and efferent cardiac autonomic balance was estimated. The heart rate measured during orthostatic stress test was lowered after thoracoscopic sympathectomy (between-group; P = 0.01) due to a change in autonomic tone, with increased vagal (high-frequency power n.u.; P = 0.001), and reduced sympathetic efferent cardiac activity (low-frequency power n.u.; P < 0.001). Baroreceptor sensitivity measured during rest was increased (26 ± 13 vs 44 ± 19 ms/mmHg; P = 0.01), and diastolic blood pressure reduced after surgery (P = 0.01). The increases in systolic blood pressure and the sympathetic marker CCV-LF in response to orthostatic stress were higher before sympathectomy, with almost no increases post-surgically (condition × group interaction; P = 0.01 and P = 0.001, respectively). We found no change in post-procedure exercise capacity, although patients had a lower peak VO2 and maximal cardiac index than controls. Thoracoscopic sympathectomy changes the autonomic tone towards increased vagal activity; this is potentially cardioprotective. To our knowledge, this is the first study to show increased baroreceptor sensitivity after thoracoscopic sympathectomy.

The role of sympathetic and vagal cardiac control on complexity of heart rate dynamics.

PubMed

Silva, Luiz Eduardo Virgilio; Silva, Carlos Alberto Aguiar; Salgado, Helio Cesar; Fazan, Rubens

2017-03-01

Analysis of heart rate variability (HRV) by nonlinear approaches has been gaining interest due to their ability to extract additional information from heart rate (HR) dynamics that are not detectable by traditional approaches. Nevertheless, the physiological interpretation of nonlinear approaches remains unclear. Therefore, we propose long-term (60 min) protocols involving selective blockade of cardiac autonomic receptors to investigate the contribution of sympathetic and parasympathetic function upon nonlinear dynamics of HRV. Conscious male Wistar rats had their electrocardiogram (ECG) recorded under three distinct conditions: basal, selective (atenolol or atropine), or combined (atenolol plus atropine) pharmacological blockade of autonomic muscarinic or β 1 -adrenergic receptors. Time series of RR interval were assessed by multiscale entropy (MSE) and detrended fluctuation analysis (DFA). Entropy over short (1 to 5, MSE 1-5 ) and long (6 to 30, MSE 6-30 ) time scales was computed, as well as DFA scaling exponents at short (α short , 5 ≤ n ≤ 15), mid (α mid , 30 ≤ n ≤ 200), and long (α long , 200 ≤ n ≤ 1,700) window sizes. The results show that MSE 1-5 is reduced under atropine blockade and MSE 6-30 is reduced under atropine, atenolol, or combined blockade. In addition, while atropine expressed its maximal effect at scale six, the effect of atenolol on MSE increased with scale. For DFA, α short decreased during atenolol blockade, while the α mid increased under atropine blockade. Double blockade decreased α short and increased α long Results with surrogate data show that the dynamics during combined blockade is not random. In summary, sympathetic and vagal control differently affect entropy (MSE) and fractal properties (DFA) of HRV. These findings are important to guide future studies. NEW & NOTEWORTHY Although multiscale entropy (MSE) and detrended fluctuation analysis (DFA) are recognizably useful prognostic/diagnostic methods, their physiological interpretation remains unclear. The present study clarifies the effect of the cardiac autonomic control on MSE and DFA, assessed during long periods (1 h). These findings are important to help the interpretation of future studies. Copyright © 2017 the American Physiological Society.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stanton, M.S.; Tuli, M.M.; Radtke, N.L.

Transmural myocardial infarction in dogs produces denervation of sympathetic nerves in viable myocardium apical to the infarct that may be arrhythmogenic. It is unknown whether sympathetic denervation occurs in humans. The purpose of this study was to use iodine-123-metaiodobenzylguanidine (MIBG), a radiolabeled guanethidine analog that is actively taken up by sympathetic nerve terminals, to image noninvasively the cardiac sympathetic nerves in patients with and without ventricular arrhythmias after myocardial infarction. Results showed that 10 of 12 patients with spontaneous ventricular tachyarrhythmias after myocardial infarction exhibited regions of thallium-201 uptake indicating viable perfused myocardium, with no MIBG uptake. Such a findingmore » is consistent with sympathetic denervation. One patient had frequent episodes of nonsustained ventricular tachycardia induced at exercise testing that was eliminated by beta-adrenoceptor blockade. Eleven of the 12 patients had ventricular tachycardia induced at electrophysiologic study and metoprolol never prevented induction. Sympathetic denervation was also detected in two of seven postinfarction patients without ventricular arrhythmias. Normal control subjects had no regions lacking MIBG uptake. This study provides evidence that regional sympathetic denervation occurs in humans after myocardial infarction and can be detected noninvasively by comparing MIBG and thallium-201 images. Although the presence of sympathetic denervation may be related to the onset of spontaneous ventricular tachyarrhythmias in some patients, it does not appear to be related to sustained ventricular tachycardia induced at electrophysiologic study.« less

Vestibular influences on autonomic cardiovascular control in humans

NASA Technical Reports Server (NTRS)

Biaggioni, I.; Costa, F.; Kaufmann, H.; Robertson, D. (Principal Investigator)

1998-01-01

There is substantial evidence that anatomical connections exist between vestibular and autonomic nuclei. Animal studies have shown functional interactions between the vestibular and autonomic systems. The nature of these interactions, however, is complex and has not been fully defined. Vestibular stimulation has been consistently found to reduce blood pressure in animals. Given the potential interaction between vestibular and autonomic pathways this finding could be explained by a reduction in sympathetic activity. However, rather than sympathetic inhibition, vestibular stimulation has consistently been shown to increase sympathetic outflow in cardiac and splanchnic vascular beds in most experimental models. Several clinical observations suggest that a link between vestibular and autonomic systems may also exist in humans. However, direct evidence for vestibular/autonomic interactions in humans is sparse. Motion sickness has been found to induce forearm vasodilation and reduce baroreflex gain, and head down neck flexion induces transient forearm and calf vasoconstriction. On the other hand, studies using optokinetic stimulation have found either very small, variable, or inconsistent changes in heart rate and blood pressure, despite substantial symptoms of motion sickness. Furthermore, caloric stimulation severe enough to produce nystagmus, dizziness, and nausea had no effect on sympathetic nerve activity measured directly with microneurography. No effect was observed on heart rate, blood pressure, or plasma norepinephrine. Several factors may explain the apparent discordance of these results, but more research is needed before we can define the potential importance of vestibular input to cardiovascular regulation and orthostatic tolerance in humans.

Children with Autism Show Altered Autonomic Adaptation to Novel and Familiar Social Partners.

PubMed

Neuhaus, Emily; Bernier, Raphael A; Beauchaine, Theodore P

2016-05-01

Social deficits are fundamental to autism spectrum disorder (ASD), and a growing body of research implicates altered functioning of the autonomic nervous system (ANS), including both sympathetic and parasympathetic branches. However, few studies have explored both branches concurrently in ASD, particularly within the context of social interaction. The current study investigates patterns of change in indices of sympathetic (pre-ejection period; PEP) and parasympathetic (respiratory sinus arrhythmia; RSA) cardiac influence as boys (ages 8-11 years) with (N = 18) and without (N = 18) ASD engage in dyadic social interaction with novel and familiar social partners. Groups showed similar patterns of autonomic change during interaction with the novel partner, but differed in heart rate, PEP, and RSA reactivity while interacting with a familiar partner. Boys without ASD evinced decreasing sympathetic and increasing parasympathetic influence, whereas boys with ASD increased in sympathetic influence. Boys without ASD also demonstrated more consistent ANS responses across partners than those with ASD, with parasympathetic responding differentiating familiar and novel interaction partners. Finally, PEP slopes with a familiar partner correlated with boys' social skills. Implications include the importance of considering autonomic state during clinical assessment and treatment, and the potential value of regulation strategies as a complement to intervention programs aiming to support social cognition and behavior. Autism Res 2016, 9: 579-591. © 2015 International Society for Autism Research, Wiley Periodicals, Inc. © 2015 International Society for Autism Research, Wiley Periodicals, Inc.

Autonomic nervous system profile in fibromyalgia patients and its modulation by exercise: a mini review.

PubMed

Kulshreshtha, Poorvi; Deepak, Kishore K

2013-03-01

This review imparts an impressionistic tone to our current understanding of autonomic nervous system abnormalities in fibromyalgia. In the wake of symptoms present in patients with fibromyalgia (FM), autonomic dysfunction seems plausible in fibromyalgia. A popular notion is that of a relentless sympathetic hyperactivity and hyporeactivity based on heart rate variability (HRV) analyses and responses to various physiological stimuli. However, some exactly opposite findings suggesting normal/hypersympathetic reactivity in patients with fibromyalgia do exist. This heterogeneous picture along with multiple comorbidities accounts for the quantitative and qualitative differences in the degree of dysautonomia present in patients with FM. We contend that HRV changes in fibromyalgia may not actually represent increased cardiac sympathetic tone. Normal muscle sympathetic nerve activity (MSNA) and normal autonomic reactivity tests in patients with fibromyalgia suggest defective vascular end organ in fibromyalgia. Previously, we proposed a model linking deconditioning with physical inactivity resulting from widespread pain in patients with fibromyalgia. Deconditioning also modulates the autonomic nervous system (high sympathetic tone and a low parasympathetic tone). A high peripheral sympathetic tone causes regional ischaemia, which in turn results in widespread pain. Thus, vascular dysregulation and hypoperfusion in patients with FM give rise to ischaemic pain leading to physical inactivity. Microvascular abnormalities are also found in patients with FM. Therapeutic interventions (e.g. exercise) that result in vasodilatation and favourable autonomic alterations have proven to be effective. In this review, we focus on the vascular end organ in patients with fibromyalgia in particular and its modulation by exercise in general. © 2012 The Authors Clinical Physiology and Functional Imaging © 2012 Scandinavian Society of Clinical Physiology and Nuclear Medicine.

Physiological basis for human autonomic rhythms

NASA Technical Reports Server (NTRS)

Eckberg, D. L.

2000-01-01

Oscillations of arterial pressures, heart periods, and muscle sympathetic nerve activity have been studied intensively in recent years to explore otherwise obscure human neurophysiological mechanisms. The best-studied rhythms are those occurring at breathing frequencies. Published evidence indicates that respiratory fluctuations of muscle sympathetic nerve activity and electrocardiographic R-R intervals result primarily from the action of a central 'gate' that opens during expiration and closes during inspiration. Parallel respiratory fluctuations of arterial pressures and R-R intervals are thought to be secondary to arterial baroreflex physiology: changes in systolic pressure provoke changes in the R-R interval. However, growing evidence suggests that these parallel oscillations result from the influence of respiration on sympathetic and vagal-cardiac motoneurones rather than from baroreflex physiology. There is a rapidly growing literature on the use of mathematical models of low- and high-frequency (respiratory) R-R interval fluctuations in characterizing instantaneous 'sympathovagal balance'. The case for this approach is based primarily on measurements made with patients in upright tilt. However, the strong linear relation between such measures as the ratio of low- to high-frequency R-R interval oscillations and the angle of the tilt reflects exclusively the reductions of the vagal (high-frequency) component. As the sympathetic component does not change in tilt, the low- to high-frequency R-R interval ratio provides no proof that sympathetic activity increases. Moreover, the validity of extrapolating from measurements performed during upright tilt to measurements during supine rest has not been established. Nonetheless, it is clear that measures of heart rate variability provide important prognostic information in patients with cardiovascular diseases. It is not known whether reduced heart rate variability is merely a marker for the severity of disease or a measurement that identifies functional reflex abnormalities contributing to terminal dysrhythmias.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Navarro-Zaragoza, J.; Martínez-Laorden, E.; Mora, L.

Opioid addiction is associated with cardiovascular disease. However, mechanisms linking opioid addiction and cardiovascular disease remain unclear. This study investigated the role of corticotropin-releasing factor (CRF) 1 receptor in mediating somatic signs and the behavioural states produced during withdrawal from morphine dependence. Furthermore, it studied the efficacy of CRF1 receptor antagonist, CP-154,526 to prevent the cardiac sympathetic activity induced by morphine withdrawal. In addition, tyrosine hydroxylase (TH) phosphorylation pathways were evaluated. Like stress, morphine withdrawal induced an increase in the hypothalamic–pituitary–adrenal (HPA) axis activity and an enhancement of noradrenaline (NA) turnover. Pre-treatment with CRF1 receptor antagonist significantly reduced morphine withdrawal-inducedmore » increases in plasma adrenocorticotropic hormone (ACTH) levels, NA turnover and TH phosphorylation at Ser31 in the right ventricle. In addition, CP-154,526 reduced the phosphorylation of extracellular signal-regulated kinase (ERK) after naloxone-precipitated morphine withdrawal. In addition, CP-154,526 attenuated the increases in body weight loss during morphine treatment and suppressed some of morphine withdrawal signs. Altogether, these results support the idea that cardiac sympathetic pathways are activated in response to naloxone-precipitated morphine withdrawal suggesting that treatment with a CRF1 receptor antagonist before morphine withdrawal would prevent the development of stress-induced behavioural and autonomic dysfunction in opioid addicts. - Highlights: • Morphine withdrawal caused an increase in myocardial sympathetic activity. • ERK regulates TH phosphorylation after naloxone-induced morphine withdrawal. • CRF1R is involved in cardiac adaptive changes during morphine dependence.« less

Premature Ventricular Contraction Coupling Interval Variability Destabilizes Cardiac Neuronal and Electrophysiological Control: Insights from Simultaneous Cardio-Neural Mapping

PubMed Central

Hamon, David; Rajendran, Pradeep S.; Chui, Ray W.; Ajijola, Olujimi A.; Irie, Tadanobu; Talebi, Ramin; Salavatian, Siamak; Vaseghi, Marmar; Bradfield, Jason S.; Armour, J. Andrew; Ardell, Jeffrey L.; Shivkumar, Kalyanam

2017-01-01

Background Variability in premature ventricular contraction (PVC) coupling interval (CI) increases the risk of cardiomyopathy and sudden death. The autonomic nervous system regulates cardiac electrical and mechanical indices, and its dysregulation plays an important role in cardiac disease pathogenesis. The impact of PVCs on the intrinsic cardiac nervous system (ICNS), a neural network on the heart, remains unknown. The objective was to determine the effect of PVCs and CI on ICNS function in generating cardiac neuronal and electrical instability using a novel cardio-neural mapping approach. Methods and Results In a porcine model (n=8) neuronal activity was recorded from a ventricular ganglion using a microelectrode array, and cardiac electrophysiological mapping was performed. Neurons were functionally classified based on their response to afferent and efferent cardiovascular stimuli, with neurons that responded to both defined as convergent (local reflex processors). Dynamic changes in neuronal activity were then evaluated in response to right ventricular outflow tract PVCs with fixed short, fixed long, and variable CI. PVC delivery elicited a greater neuronal response than all other stimuli (P<0.001). Compared to fixed short and long CI, PVCs with variable CI had a greater impact on neuronal response (P<0.05 versus short CI), particularly on convergent neurons (P<0.05), as well as neurons receiving sympathetic (P<0.05) and parasympathetic input (P<0.05). The greatest cardiac electrical instability was also observed following variable (short) CI PVCs. Conclusions Variable CI PVCs affect critical populations of ICNS neurons and alter cardiac repolarization. These changes may be critical for arrhythmogenesis and remodeling leading to cardiomyopathy. PMID:28408652

Renal sympathetic denervation attenuates hypertension and vascular remodeling in renovascular hypertensive rats.

PubMed

Li, Peng; Huang, Pei-Pei; Yang, Yun; Liu, Chi; Lu, Yan; Wang, Fang; Sun, Wei; Kong, Xiang-Qing

2017-01-01

Li P, Huang P, Yang Y, Liu C, Lu Y, Wang F, Sun W, Kong X. Renal sympathetic denervation attenuates hypertension and vascular remodeling in renovascular hypertensive rats. J Appl Physiol 122: 121-129, 2017. First published October 14, 2016; doi:10.1152/japplphysiol.01019.2015-Sympathetic activity is enhanced in patients with essential or secondary hypertension, as well as in various hypertensive animal models. Therapeutic targeting of sympathetic activation is considered an effective antihypertensive strategy. We hypothesized that renal sympathetic denervation (RSD) attenuates hypertension and improves vascular remodeling and renal disease in the 2-kidney, 1-clip (2K1C) rat model. Rats underwent 2K1C modeling or sham surgery; then rats underwent RSD or sham surgery 4 wk later, thus resulting in four groups (normotensive-sham, normotensive-RSD, 2K1C-sham, and 2K1C-RSD). Norepinephrine was measured by ELISA. Echocardiography was used to assess heart function. Fibrosis and apoptosis were assessed by Masson and TUNEL staining. Changes in mean arterial blood pressure in response to hexamethonium and plasma norepinephrine levels were used to evaluate basal sympathetic nerve activity. The 2K1C modeling success rate was 86.8%. RSD reversed the elevated systolic blood pressure induced by 2K1C, but had no effect on body weight. Compared with rats in the 2K1C-sham group, rats in the 2K1C-RSD group showed lower left ventricular mass/body weight ratio, interventricular septal thickness in diastole, left ventricular end-systolic diameter, and left ventricular posterior wall thickness in systole, whereas fractional shortening and ejection fraction were higher. Right kidney apoptosis and left kidney hypertrophy were not changed by RSD. Arterial fibrosis was lower in animals in the 2K1C-RSD group compared with those in the 2K1C-sham group. RSD reduced plasma norepinephrine and basal sympathetic activity in rats in the 2K1C-RSD group compared with rats in the 2K1C-sham group. These results suggest a possible clinical efficacy of RSD for renovascular hypertension. The effects of renal sympathetic denervation (RSD) on hypertension, cardiac function, vascular fibrosis, and renal apoptosis were studied in the 2K1C rat model. Results showed that RSD attenuated hypertension, improved vascular remodeling, and reduced vascular fibrosis through decreased sympathetic activity in the 2K1C rat model, but it did not change the kidney size, renal apoptosis, or renal caspase-3 expression. These results could suggest possible clinical efficacy of RSD for renovascular hypertension. Copyright © 2017 the American Physiological Society.

P2X receptors in the cardiovascular system and their potential as therapeutic targets in disease.

PubMed

Ralevic, Vera

2015-01-01

This review considers the expression and roles of P2X receptors in the cardiovascular system in health and disease and their potential as therapeutic targets. P2X receptors are ligand gated ion channels which are activated by the endogenous ligand ATP. They are formed from the assembly of three P2X subunit proteins from the complement of seven (P2X1-7), which can associate to form homomeric or heteromeric P2X receptors. The P2X1 receptor is widely expressed in the cardiovascular system, being located in the heart, in the smooth muscle of the majority of blood vessels and in platelets. P2X1 receptors expressed in blood vessels can be activated by ATP coreleased with noradrenaline as a sympathetic neurotransmitter, leading to smooth muscle depolarisation and contraction. There is evidence that the purinergic component of sympathetic neurotransmission is increased in hypertension, identifying P2X1 receptors as a possible therapeutic target in this disorder. P2X3 and P2X2/3 receptors are expressed on cardiac sympathetic neurones and may, through positive feedback of neuronal ATP at this prejunctional site, amplify sympathetic neurotransmission. Activation of P2X receptors expressed in the heart increases cardiac myocyte contractility, and an important role of the P2X4 receptor in this has been identified. Deletion of P2X4 receptors in the heart depresses contractile performance in models of heart failure, while overexpression of P2X4 receptors has been shown to be cardioprotective, thus P2X4 receptors may be therapeutic targets in the treatment of heart disease. P2X receptors have been identified on endothelial cells. Although immunoreactivity for all P2X1-7 receptor proteins has been shown on the endothelium, relatively little is known about their function, with the exception of the endothelial P2X4 receptor, which has been shown to mediate endothelium-dependent vasodilatation to ATP released during shear stress. The potential of P2X receptors as therapeutic targets in the treatment of cardiovascular disease is discussed.

Heart rate and cardiovascular variability at high altitude.

PubMed

Bernardi, Luciano

2007-01-01

Primary effect of hypobaric hypoxia on the circulation is a direct vasodilatory effect on the peripheral circulation, which is normally prevented by a sympathetic-induced vasoconstriction. Most of the clinical methods for testing the baroreflex sensitivity only evaluate the cardiac-vagal branch of the baroreflex, but at altitude it is also of importance to test the vascular effects of the baroreflex. This is possible by directly measuring sympathetic efferent activity (by microneurography) or by directly stimulating the carotid baroreceptors (by the neck suction). By cyclical stimulation of the carotid baroreceptors, neck suction-synchronous reflex oscillations could be observed in a large number of signals, including RR interval, blood pressure, microcirculation, muscle sympathetic nerve activity. An increase in fluctuations at the same frequency of the stimulus was considered an evidence of the ability of the carotid baroreceptors to modulate a given physiological signal. The sinusoidal neck suction was set at 0.10 Hz (low-frequency stimulation), or to a frequency close to- but distinct from- the respiratory signal (0.20 Hz, high frequency stimulation, whereas respiration was fixed to 0.25 Hz). The method is noninvasive, without side effects connected to use of drugs, and evaluates both the response to the heart and to the blood pressure of the baroreflex. The altitude-induced sympathetic activation was evidenced in sea level natives by a decrease in RR interval, an increase in blood pressure and in the 0.1Hz components of cardiac and vascular signals. The arterial baroflex was active on RR interval and also in blood pressure, even during acute exposure to high altitude, thus indicating that it was counteracting and modulating the increase in sympathetic tone. Signs of exaggerated sympathetic activation were evident in subjects with severe acute mountain sickness, while successful therapy was associated with a restoration of autonomic modulation. Conversely, sympathetic activation was reduced( and baroflex enhanced) in himalayan high altitude natives. In conclusion, a comprehensive understanding of the mechanism taking place during the adaptation to high altitude requires a multisignal approach, also integrated with equipment designed to provide specific provocative tests, such as those necessary to measure the cardiorespiratory interactions.

Psychological traits influence autonomic nervous system recovery following esophageal intubation in health and functional chest pain.

PubMed

Farmer, A D; Coen, S J; Kano, M; Worthen, S F; Rossiter, H E; Navqi, H; Scott, S M; Furlong, P L; Aziz, Q

2013-12-01

Esophageal intubation is a widely utilized technique for a diverse array of physiological studies, activating a complex physiological response mediated, in part, by the autonomic nervous system (ANS). In order to determine the optimal time period after intubation when physiological observations should be recorded, it is important to know the duration of, and factors that influence, this ANS response, in both health and disease. Fifty healthy subjects (27 males, median age 31.9 years, range 20-53 years) and 20 patients with Rome III defined functional chest pain (nine male, median age of 38.7 years, range 28-59 years) had personality traits and anxiety measured. Subjects had heart rate (HR), blood pressure (BP), sympathetic (cardiac sympathetic index, CSI), and parasympathetic nervous system (cardiac vagal tone, CVT) parameters measured at baseline and in response to per nasum intubation with an esophageal catheter. CSI/CVT recovery was measured following esophageal intubation. In all subjects, esophageal intubation caused an elevation in HR, BP, CSI, and skin conductance response (SCR; all p < 0.0001) but concomitant CVT and cardiac sensitivity to the baroreflex (CSB) withdrawal (all p < 0.04). Multiple linear regression analysis demonstrated that longer CVT recovery times were independently associated with higher neuroticism (p < 0.001). Patients had prolonged CSI and CVT recovery times in comparison to healthy subjects (112.5 s vs 46.5 s, p = 0.0001 and 549 s vs 223.5 s, p = 0.0001, respectively). Esophageal intubation activates a flight/flight ANS response. Future studies should allow for at least 10 min of recovery time. Consideration should be given to psychological traits and disease status as these can influence recovery. © 2013 John Wiley & Sons Ltd.

Neonatal autonomic function after pregnancy complications and early cardiovascular development.

PubMed

Aye, Christina Y L; Lewandowski, Adam James; Oster, Julien; Upton, Ross; Davis, Esther; Kenworthy, Yvonne; Boardman, Henry; Yu, Grace Z; Siepmann, Timo; Adwani, Satish; McCormick, Kenny; Sverrisdottir, Yrsa B; Leeson, Paul

2018-05-23

Heart rate variability (HRV) has emerged as a predictor of later cardiac risk. This study tested whether pregnancy complications that may have long-term offspring cardiac sequelae are associated with differences in HRV at birth, and whether these HRV differences identify abnormal cardiovascular development in the postnatal period. Ninety-eight sleeping neonates had 5-min electrocardiogram recordings at birth. Standard time and frequency domain parameters were calculated and related to cardiovascular measures at birth and 3 months of age. Increasing prematurity, but not maternal hypertension or growth restriction, was associated with decreased HRV at birth, as demonstrated by a lower root mean square of the difference between adjacent NN intervals (rMSSD) and low (LF) and high-frequency power (HF), with decreasing gestational age (p < 0.001, p = 0.009 and p = 0.007, respectively). We also demonstrated a relative imbalance between sympathetic and parasympathetic tone, compared to the term infants. However, differences in autonomic function did not predict cardiovascular measures at either time point. Altered cardiac autonomic function at birth relates to prematurity rather than other pregnancy complications and does not predict cardiovascular developmental patterns during the first 3 months post birth. Long-term studies will be needed to understand the relevance to cardiovascular risk.

The effects of different physical activities on atrial fibrillation in patients with hypertension and chronic kidney disease.

PubMed

Kiuchi, Márcio Galindo; Chen, Shaojie; Hoye, Neil Alexander

2017-09-01

Atrial fibrillation (AF) is highly common, and is most frequently observed in individuals with hypertension and structural cardiac disease. Sympathetic hyperactivity plays a fundamental role in the progression, maintenance and aggravation of arrhythmia. Endurance exercise training clearly lowers sympathetic activity in sympathoexcitatory disease states, and is well-tolerated by patients with chronic kidney disease (CKD). We assessed 50 CKD patients with hypertension. Each patient provided a complete medical history and underwent a physical examination. We used an implantable cardiac monitor over a 3-year follow-up period to evaluate the effects of high-intensity interval training (HIIT) and moderate exercise (ModEx) physical activity protocols on AF occurrence, and determined the effectiveness of these protocols in improving renal function. Subjects were followed up every 6 months after the beginning of the intervention. During the 3-year follow-up, AF onset was higher in CKD patients who engaged in HIIT (72%) than in those who engaged in ModEx (24%) (hazard ratio, 3.847; 95% confidence interval, 1.694-8.740, P = 0.0013 by log-rank test). Both groups exhibited significant intra-group changes in the mean systolic 24-hour ambulatory blood pressure measurements (ABPM) between baseline and 12, 24, and 36 months. There were also significant differences in the mean systolic 24-hour ABPM between the groups at the same time points. In CKD patients with hypertension, improvements in AF onset, renal function and some echocardiographic parameters were more evident in subjects who engaged in ModEx than in those who engaged in HIIT during 3 years of follow-up.

Direct projections from hypothalamic orexin neurons to brainstem cardiac vagal neurons.

PubMed

Dergacheva, Olga; Yamanaka, Akihiro; Schwartz, Alan R; Polotsky, Vsevolod Y; Mendelowitz, David

2016-12-17

Orexin neurons are known to augment the sympathetic control of cardiovascular function, however the role of orexin neurons in parasympathetic cardiac regulation remains unclear. To test the hypothesis that orexin neurons contribute to parasympathetic control we selectively expressed channelrhodopsin-2 (ChR2) in orexin neurons in orexin-Cre transgenic rats and examined postsynaptic currents in cardiac vagal neurons (CVNs) in the dorsal motor nucleus of the vagus (DMV). Simultaneous photostimulation and recording in ChR2-expressing orexin neurons in the lateral hypothalamus resulted in reliable action potential firing as well as large whole-cell currents suggesting a strong expression of ChR2 and reliable optogenetic excitation. Photostimulation of ChR2-expressing fibers in the DMV elicited short-latency (ranging from 3.2ms to 8.5ms) postsynaptic currents in 16 out of 44 CVNs tested. These responses were heterogeneous and included excitatory glutamatergic (63%) and inhibitory GABAergic (37%) postsynaptic currents. The results from this study suggest different sub-population of orexin neurons may exert diverse influences on brainstem CVNs and therefore may play distinct functional roles in parasympathetic control of the heart. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

Prevalence and pattern of cardiac autonomic dysfunction in newly detected type 2 diabetes mellitus.

PubMed

Jyotsna, Viveka P; Sahoo, Abhay; Sreenivas, V; Deepak, K K

2009-01-01

Cardiac autonomic functions were assessed in 145 consecutive recently detected type 2 diabetics. Ninety-nine healthy persons served as controls. Criteria for normalcy were, heart rate variation during deep breathing >or=15 beats/min, deep breathing expiratory to inspiratory R-R ratio >or=1.21, Valsalva ratio >or=1.21, sustained handgrip test >or=16 mm of mercury, cold pressor test >or=10, BP response to standing or=1.04. An abnormal test was defined as the above parameters being <10 beats/min, <1.21, <1.21, or=30 mm of mercury and

Effects of cigarette smoking on cardiac autonomic function during dynamic exercise.

PubMed

Mendonca, Goncalo V; Pereira, Fernando D; Fernhall, Bo

2011-06-01

The purpose of this study was to investigate the acute effect of cigarette smoking on cardiac autonomic function in young adult smokers during dynamic exercise. Fourteen healthy young smokers (21.4 ± 3.4 years) performed peak and submaximal exercise protocols under control and smoking conditions. Resting and submaximal beat-to-beat R-R series were recorded and spectrally decomposed using the fast Fourier transformation. Smoking resulted in a significant decrease in work time, VO(2peak) and peak O(2) pulse (P < 0.05). Heart rate increased at rest and during submaximal exercise after smoking (P < 0.05). The raw high frequency and low frequency power were significantly reduced by smoking, both at rest and during exercise (P < 0.05). The low to high frequency ratio was higher after smoking (P < 0.05). The normalised low frequency power was also significantly increased by smoking, but only at rest (P < 0.05). These data demonstrate that the tachycardic effect elicited by smoking is accompanied by acute changes in heart rate spectral components both at rest and during exercise. Therefore, the cardiac autonomic control is altered by smoking not only at rest, but also during exercise, resulting in reduced vagal modulation and increased sympathetic dominance.

Effects of whole-body vibration on heart rate variability: acute responses and training adaptations.

PubMed

Wong, Alexei; Figueroa, Arturo

2018-05-18

Heart rate variability (HRV) is a noninvasive and practical measure of cardiac autonomic nervous system function, mainly the sympathetic and parasympathetic modulations of heart rate. A low HRV has been shown to be indicative of compromised cardiovascular health. Interventions that enhance HRV are therefore beneficial to cardiovascular health. Whole-body vibration (WBV) training has been proposed as an alternative time-efficient exercise intervention for the improvement of cardiovascular health. In this review, we discuss the effect of WBV both acute and after training on HRV. WBV training appears to be a useful therapeutic intervention to improve cardiac autonomic function in different populations, mainly through decreases in sympathovagal balance. Although the mechanisms by which WBV training improves symphathovagal balance are not yet well understood; enhancement of baroreflex sensitivity, nitric oxide bioavailability and angiotensin II levels seem to play an important role. © 2018 Scandinavian Society of Clinical Physiology and Nuclear Medicine. Published by John Wiley & Sons Ltd.

Cardiac response to whole-body heating

DOE Office of Scientific and Technical Information (OSTI.GOV)

Frey, M.A.B.; Kenney, R.A.

1979-04-01

Systolic time interval analysis was used to assess changes in ventricular function during heat stress. Seven subjects (4 M + 3 F, 22-35 yr) participated in the experiments. The heating procedure was the following: both legs of seated subjects were immersed to the knees in stirred water maintained at 42-45 C. The subjects' upper legs and trunks were enclosed in nonpermeable plastic and covered with a sheet blanket to reduce heat loss. After 30 min of heating, the water and plastic were removed. The parameters measured were HR and R-R interval, LVET, and PEP. Results were compared by t testmore » at the 0.05 significance level. The results pointed to a two-stage cardiac response to heat-vagal withdrawal followed by a strong sympathetic outflow to the heart affecting both inotropic and chronotropic characteristics.« less

Cardiac sympathetic denervation and dementia in de novo Parkinson's disease: A 7-year follow-up study.

PubMed

Choi, Mun Hee; Yoon, Jung Han; Yong, Suk Woo

2017-10-15

Postganglionic cardiac sympathetic denervation is evident in patients with early-stage Parkinson's disease (PD). Cardiac iodine-123-meta-iodobenzylguanidine (MIBG) uptake is correlated with the non-motor symptoms of PD, suggesting that low cardiac MIBG uptake may reflect wider alpha-synuclein pathology. In addition, low cardiac MIBG could be related to orthostatic hypotension in PD, which may affect cognition. However, the prognostic validity of baseline MIBG scintigraphy in terms of the risk of subsequent dementia remains unclear. We investigated whether cardiac MIBG uptake was associated with a later risk of dementia. We retrospectively enrolled 93 drug-naive patients with de novo PD who underwent MIBG scanning on initial evaluation. The patients visited our outpatient clinic every 3-6months and were followed-up for a minimum of 4years from the time they were begun on dopaminergic medication. The predictive powers of baseline MIBG cardiac scintigraphic data in terms of dementia development were evaluated using Cox's proportional hazard models. During a mean follow-up period of 6.7years, 27 patients with PD (29.0%) developed dementia. These patients had less baseline MIBG uptake than did others (delayed H/M ratios: 1.19 vs. 1.31). Multivariate Cox's proportional hazard modeling revealed that both MIBG uptake (hazard ratio [HR] 3.40; p=0.004) and age (HR 1.08, p=0.01) significantly predicted dementia development. A reduction in cardiac MIBG uptake by PD patients may be associated with a subsequent risk of dementia; reduced uptake may reflect wider extension of alpha-synuclein pathology in PD. Copyright © 2017 Elsevier B.V. All rights reserved.

Effects of acute and chronic exercise in patients with essential hypertension: benefits and risks.

PubMed

Gkaliagkousi, Eugenia; Gavriilaki, Eleni; Douma, Stella

2015-04-01

The importance of regular physical activity in essential hypertension has been extensively investigated over the last decades and has emerged as a major modifiable factor contributing to optimal blood pressure control. Aerobic exercise exerts its beneficial effects on the cardiovascular system by promoting traditional cardiovascular risk factor regulation, as well as by favorably regulating sympathetic nervous system (SNS) activity, molecular effects, cardiac, and vascular function. Benefits of resistance exercise need further validation. On the other hand, acute exercise is now an established trigger of acute cardiac events. A number of possible pathophysiological links have been proposed, including SNS, vascular function, coagulation, fibrinolysis, and platelet function. In order to fully interpret this knowledge into clinical practice, we need to better understand the role of exercise intensity and duration in this pathophysiological cascade and in special populations. Further studies in hypertensive patients are also warranted in order to clarify the possibly favorable effect of antihypertensive treatment on exercise-induced effects. © American Journal of Hypertension, Ltd 2014. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

New radionuclide agents for cardiac imaging: Description and application

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kahn, J.K.; Pippin, J.J.; Corbett, J.R.

1989-08-01

The introduction of three new radiopharmaceuticals into clinical research and practice has broadened the potential applications and scope of nuclear cardiology examinations. Technetium-99m labeled isonitrile perfusion agents have excellent imaging characteristics allowing the accurate identification of coronary artery disease. Simultaneous assessments of ventricular function are possible with these agents. Iodine-123 phenylpentadecanoic acid myocardial scintigraphy permits assessments of myocardial perfusion and fatty acid metabolism, and permits investigations of myocardial metabolism with conventional imaging equipment. Iodine-123 meta-iodobenzyl-guanidine serves as an indicator of the functional integrity of the sympathetic nervous system and permits evaluations of the effects of various disease states on catecholaminemore » handling by the heart. 58 references.« less

Respiratory modulation of human autonomic rhythms

NASA Technical Reports Server (NTRS)

Badra, L. J.; Cooke, W. H.; Hoag, J. B.; Crossman, A. A.; Kuusela, T. A.; Tahvanainen, K. U.; Eckberg, D. L.

2001-01-01

We studied the influence of three types of breathing [spontaneous, frequency controlled (0.25 Hz), and hyperventilation with 100% oxygen] and apnea on R-R interval, photoplethysmographic arterial pressure, and muscle sympathetic rhythms in nine healthy young adults. We integrated fast Fourier transform power spectra over low (0.05-0.15 Hz) and respiratory (0.15-0.3 Hz) frequencies; estimated vagal baroreceptor-cardiac reflex gain at low frequencies with cross-spectral techniques; and used partial coherence analysis to remove the influence of breathing from the R-R interval, systolic pressure, and muscle sympathetic nerve spectra. Coherence among signals varied as functions of both frequency and time. Partialization abolished the coherence among these signals at respiratory but not at low frequencies. The mode of breathing did not influence low-frequency oscillations, and they persisted during apnea. Our study documents the independence of low-frequency rhythms from respiratory activity and suggests that the close correlations that may exist among arterial pressures, R-R intervals, and muscle sympathetic nerve activity at respiratory frequencies result from the influence of respiration on these measures rather than from arterial baroreflex physiology. Most importantly, our results indicate that correlations among autonomic and hemodynamic rhythms vary over time and frequency, and, thus, are facultative rather than fixed.

Sleep-disordered breathing, impaired cardiac adrenergic innervation and prognosis in heart failure.

PubMed

Scala, Oriana; Paolillo, Stefania; Formisano, Roberto; Pellegrino, Teresa; Rengo, Giuseppe; Gargiulo, Paola; De Michele, Fausto; Starace, Antonio; Rapacciuolo, Antonio; Parisi, Valentina; Prastaro, Maria; Piscopo, Valentina; Dellegrottaglie, Santo; Bruzzese, Dario; De Martino, Fabiana; Parente, Antonio; Leosco, Dario; Trimarco, Bruno; Cuocolo, Alberto; Perrone-Filardi, Pasquale

2016-06-23

Unfavourable effects of sleep-disordered breathing (SDB) in heart failure (HF) are mainly mediated by impaired sympathetic activity. Few data are available on SDB and cardiac adrenergic impairment evaluated at myocardial level. The aim of the study was to assess the relationship between SDB, cardiac sympathetic innervation assessed by 123 I-metaiodobenzylguanidine ( 123 I-MIBG) imaging and prognosis in HF. Observational, prospective study enrolling patients with HF and reduced systolic function. Patients underwent nocturnal cardiorespiratory monitoring to assess SDB presence by apnoea/hypopnoea index (AHI), and 123 I-MIBG imaging to calculate heart-to-mediastinum (H/M) ratios and washout rate. Patients were prospectively followed for 29±18 months for the combined endpoint of cardiovascular death and HF hospitalisation. Ninety-four patients (66.1±9.8 years; left ventricular ejection fraction 32±7%) were enrolled; 72 (77%) showed SDB and, compared with non-SDB, significantly reduced early (1.67±0.22 vs 1.77±0.13; p=0.019) and late H/M ratios (1.50±0.22 vs 1.61±0.23; p=0.038). Dividing patients into two groups according to SDB severity, patients with a moderate-severe disturbance (AHI >15; n=43) showed significantly worse survival for the composite study outcome (log-rank test, p=0.001) with respect to patients with mild or no disorder (AHI ≤15; n=51). Adding SDB variables to the already known prognostic role of 123 I-MIBG imaging, we observed a worse survival in patients with both SDB and H/M impairment. Patients with systolic HF and SDB show more impaired cardiac adrenergic innervation assessed by 123 I-MIBG imaging, and more adverse prognosis compared with HF patients without SDB. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Zebrafish heart as a model to study the integrative autonomic control of pacemaker function

PubMed Central

Stoyek, Matthew R.; Quinn, T. Alexander; Croll, Roger P.

2016-01-01

The cardiac pacemaker sets the heart's primary rate, with pacemaker discharge controlled by the autonomic nervous system through intracardiac ganglia. A fundamental issue in understanding the relationship between neural activity and cardiac chronotropy is the identification of neuronal populations that control pacemaker cells. To date, most studies of neurocardiac control have been done in mammalian species, where neurons are embedded in and distributed throughout the heart, so they are largely inaccessible for whole-organ, integrative studies. Here, we establish the isolated, innervated zebrafish heart as a novel alternative model for studies of autonomic control of heart rate. Stimulation of individual cardiac vagosympathetic nerve trunks evoked bradycardia (parasympathetic activation) and tachycardia (sympathetic activation). Simultaneous stimulation of both vagosympathetic nerve trunks evoked a summative effect. Effects of nerve stimulation were mimicked by direct application of cholinergic and adrenergic agents. Optical mapping of electrical activity confirmed the sinoatrial region as the site of origin of normal pacemaker activity and identified a secondary pacemaker in the atrioventricular region. Strong vagosympathetic nerve stimulation resulted in a shift in the origin of initial excitation from the sinoatrial pacemaker to the atrioventricular pacemaker. Putative pacemaker cells in the sinoatrial and atrioventricular regions expressed adrenergic β2 and cholinergic muscarinic type 2 receptors. Collectively, we have demonstrated that the zebrafish heart contains the accepted hallmarks of vertebrate cardiac control, establishing this preparation as a viable model for studies of integrative physiological control of cardiac function by intracardiac neurons. PMID:27342878

The Effects of Endurance Exercise Training on the Coronary Vascular Responsiveness to Intracoronary Acetylcholine in Swine

DTIC Science & Technology

1993-04-09

systems. The mechanisms of sympathet ic innervation involve a-adrenergic-mediated coronary vascular smooth muscle contraction, and (1- adrenergic-mediated...may cause muscarinic-mediated relaxation or contraction of vascular smooth muscle , depending on the animal species and presence of endothelial...both cardiac muscle layers receive equal flows over a cardiac cycle, regardless of the differences from systo lic compression (Buckberg and Kattus

Isoform variants of troponin in skeletal and cardiac muscle cells cultured with and without nerves.

PubMed

Toyota, N; Shimada, Y

1983-05-01

Immunofluorescence microscopy shows that cultured skeletal and cardiac muscle cells of chicken embryos exhibit the same stainabilities with antibodies against skeletal and cardiac troponin components as do those in embryos. Muscle cells of each type cultured with motor or sympathetic nerves or in medium containing the nerve extract exhibit the same reactivities as do those in adult animals. Cardiac muscle cells incubated in the nerve-conditioned medium also change the form of troponin components to the adult type. It appears that the differentiation of individual muscle fibers to specific types is induced by nerves, and especially by the neurohumoral effect.

Juvenile onset depression alters cardiac autonomic balance in response to psychological and physical challenges

PubMed Central

Bylsma, Lauren M.; Yaroslavsky, Ilya; Rottenberg, Jonathan; Jennings, J. Richard; George, Charles J.; Kiss, Enikő; Kapornai, Krisztina; Halas, Kitti; Dochnal, Roberta; Lefkovics, Eszter; Benák, István; Baji, Ildikó; Vetró, Ágnes; Kovacs, Maria

2015-01-01

Cardiac autonomic balance (CAB) indexes the ratio of parasympathetic to sympathetic activation (Berntson, Norman, Hawkley, & Cacioppo, 2008), and is believed to reflect overall autonomic flexibility in the face of environmental challenges. However, CAB has not been examined in depression. We examined changes in CAB and other physiological variables in 179 youth with a history of juvenile onset depression (JOD) and 161 healthy controls, in response to two psychological (unsolvable puzzle, sad film) and two physical (handgrip, and forehead cold pressor) challenges. In repeated measures analyses, controls showed expected reductions in CAB for both the handgrip and unsolvable puzzle, reflecting a shift to sympathetic relative to parasympathetic activation. By contrast, JOD youth showed increased CAB from baseline for both tasks (ps<.05). No effects were found for the forehead cold pressor or sad film tasks, suggesting that CAB differences may arise under conditions requiring greater attentional control or sustained effort. PMID:26225465

Creative motivation: creative achievement predicts cardiac autonomic markers of effort during divergent thinking.

PubMed

Silvia, Paul J; Beaty, Roger E; Nusbaum, Emily C; Eddington, Kari M; Kwapil, Thomas R

2014-10-01

Executive approaches to creativity emphasize that generating creative ideas can be hard and requires mental effort. Few studies, however, have examined effort-related physiological activity during creativity tasks. Using motivational intensity theory as a framework, we examined predictors of effort-related cardiac activity during a creative challenge. A sample of 111 adults completed a divergent thinking task. Sympathetic (PEP and RZ) and parasympathetic (RSA and RMSSD) outcomes were assessed using impedance cardiography. As predicted, people with high creative achievement (measured with the Creative Achievement Questionnaire) showed significantly greater increases in sympathetic activity from baseline to task, reflecting higher effort. People with more creative achievements generated ideas that were significantly more creative, and creative performance correlated marginally with PEP and RZ. The results support the view that creative thought can be a mental challenge. Copyright © 2014 Elsevier B.V. All rights reserved.

Neuroaxial anaesthesia in obstetrical patients with cardiac disease.

PubMed

Gomar, Carmen; Errando, Carlos L

2005-10-01

Pregnancy and the peripartum period represent a physiological burden for the cardiac patient that can worsen even moderate degrees of cardiac disease. Valvular stenotic diseases, congenital cardiac disease, and coronary insufficiency are relatively frequent in pregnant patients. Since considerable variability exists in the cardiovascular changes and responses to labour among different cardiac diseases and their functional status, recommendations for anaesthetic management are based on reported clinical experience and pathophysiological concepts. Neuroaxial blockade reduces or even abolishes the cardiovascular stress response to pain, mitigates Valsalva effects by decreasing the pushing reflex, and allows the adaptation of analgesia or anaesthesia to labour stage and delivery. Sympathetic blockade caused by standard neuroaxial techniques, however, reduces systemic vascular resistance and cardiac preload followed by reflex tachycardia. Recent development of neuroaxial techniques with spinal opiates for the first stage of labour, carefully titrated segmental epidural analgesia with opiates combined with low concentrations of local anaesthetic for the second stage, and even low spinal anaesthesia for vaginal instrumental delivery, have all been used with good results in patients with severe cardiac disease. Only Tetralogy of Fallot, primary pulmonary hypertension, idiopathic hypertrophic subaortic stenosis, and anticoagulation are considered relative or absolute contraindications for neuroaxial techniques, though slow segmental blockade of dermatomes may offer an alternative. For Caesarean section, single shot spinal anaesthesia is not recommended in moderate or severe heart disease. Adequate cardiovascular invasive monitoring is essential and should be administered and maintained in the postpartum period with the same criteria that reduce morbidity and mortality in cardiac patients undergoing general surgery.

Exercise training preserves vagal preganglionic neurones and restores parasympathetic tonus in heart failure.

PubMed

Ichige, Marcelo H A; Santos, Carla R; Jordão, Camila P; Ceroni, Alexandre; Negrão, Carlos E; Michelini, Lisete C

2016-11-01

Heart Failure (HF) is accompanied by reduced ventricular function, activation of compensatory neurohormonal mechanisms and marked autonomic dysfunction characterized by exaggerated sympathoexcitation and reduced parasympathetic activity. With 6 weeks of exercise training, HF-related loss of choline acetyltransferase (ChAT)-positive vagal preganglionic neurones is avoided, restoring the parasympathetic tonus to the heart, and the immunoreactivity of dopamine β-hydroxylase-positive premotor neurones that drive sympathetic outflow to the heart is reduced. Training-induced correction of autonomic dysfunction occurs even with the persistence of abnormal ventricular function. Strong positive correlation between improved parasympathetic tonus to the heart and increased ChAT immunoreactivity in vagal preganglionic neurones after training indicates this is a crucial mechanism to restore autonomic function in heart failure. Exercise training is an efficient tool to attenuate sympathoexcitation, a hallmark of heart failure (HF). Although sympathetic modulation in HF is widely studied, information regarding parasympathetic control is lacking. We examined the combined effects of sympathetic and vagal tonus to the heart in sedentary (Sed) and exercise trained (ET) HF rats and the contribution of respective premotor and preganglionic neurones. Wistar rats submitted to coronary artery ligation or sham surgery were assigned to training or sedentary protocols for 6 weeks. After haemodynamic, autonomic tonus (atropine and atenolol i.v.) and ventricular function determinations, brains were collected for immunoreactivity assays (choline acetyltransferase, ChATir; dopamine β-hydroxylase, DBHir) and neuronal counting in the dorsal motor nucleus of vagus (DMV), nucleus ambiguus (NA) and rostroventrolateral medulla (RVLM). HF-Sed vs. SHAM-Sed exhibited decreased exercise capacity, reduced ejection fraction, increased left ventricle end diastolic pressure, smaller positive and negative dP/dt, decreased intrinsic heart rate (IHR), lower parasympathetic and higher sympathetic tonus, reduced preganglionic vagal neurones and ChATir in the DMV/NA, and increased RVLM DBHir. Training increased treadmill performance, normalized autonomic tonus and IHR, restored the number of DMV and NA neurones and corrected ChATir without affecting ventricular function. There were strong positive correlations between parasympathetic tonus and ChATir in NA and DMV. RVLM DBHir was also normalized by training, but there was no change in neurone number and no correlation with sympathetic tonus. Training-induced preservation of preganglionic vagal neurones is crucial to normalize parasympathetic activity and restore autonomic balance to the heart even in the persistence of cardiac dysfunction. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

The sympathetic nervous system in polycystic ovary syndrome: a novel therapeutic target?

PubMed

Lansdown, Andrew; Rees, D Aled

2012-12-01

Polycystic ovary syndrome (PCOS) is a common endocrine condition associated with long-term health risks, including type 2 diabetes and vascular dysfunction in addition to reproductive sequelae. Many of the common features of PCOS, such as central obesity, hyperinsulinaemia and obstructive sleep apnoea (OSA), are associated with chronic sympathetic overactivity, suggesting that sympathoexcitation may be involved in the pathogenesis of this condition. Rodent models of polycystic ovaries have shown that ovarian sympathetic outflow may be increased, accompanied by elevated intra-ovarian synthesis of nerve growth factor (NGF) which may be involved in initiation of ovarian pathology. Patients with PCOS have evidence of increased muscle sympathetic nerve activity (MSNA), altered heart rate variability and attenuated heart rate recovery postexercise, compared with age- and BMI-matched controls, suggesting a generalized increase in sympathetic nerve activity. Active weight loss can reduce MSNA and whole body noradrenaline spillover, whereas low-frequency electroacupuncture decreased MSNA in overweight women with PCOS. Treatment of OSA with continuous positive airways pressure may reduce plasma noradrenaline levels and diastolic blood pressure and improve cardiac sympathovagal balance. Renal sympathetic denervation also reduced MSNA, noradrenaline spillover and blood pressure in two PCOS subjects with hypertension, accompanied by improved insulin sensitivity. The sympathetic nervous system may thus offer a new therapeutic target in PCOS but larger and longer-term studies are needed before these treatments can be considered in clinical practice. © 2012 Blackwell Publishing Ltd.

Dorsal spinal cord stimulation obtunds the capacity of intrathoracic extracardiac neurons to transduce myocardial ischemia

PubMed Central

Ardell, Jeffrey L.; Cardinal, René; Vermeulen, Michel; Armour, J. Andrew

2009-01-01

Populations of intrathoracic extracardiac neurons transduce myocardial ischemia, thereby contributing to sympathetic control of regional cardiac indices during such pathology. Our objective was to determine whether electrical neuromodulation using spinal cord stimulation (SCS) modulates such local reflex control. In 10 anesthetized canines, middle cervical ganglion neurons were identified that transduce the ventricular milieu. Their capacity to transduce a global (rapid ventricular pacing) vs. regional (transient regional ischemia) ventricular stress was tested before and during SCS (50 Hz, 0.2 ms duration at 90% MT) applied to the dorsal aspect of the T1 to T4 spinal cord. Rapid ventricular pacing and transient myocardial ischemia both activated cardiac-related middle cervical ganglion neurons. SCS obtunded their capacity to reflexly respond to the regional ventricular ischemia, but not rapid ventricular pacing. In conclusion, spinal cord inputs to the intrathoracic extracardiac nervous system obtund the latter's capacity to transduce regional ventricular ischemia, but not global cardiac stress. Given the substantial body of literature indicating the adverse consequences of excessive adrenergic neuronal excitation on cardiac function, these data delineate the intrathoracic extracardiac nervous system as a potential target for neuromodulation therapy in minimizing such effects. PMID:19515981

Oxygen Desaturation Index Estimation through Unconstrained Cardiac Sympathetic Activity Assessment Using Three Ballistocardiographic Systems.

PubMed

Jung, Da Woon; Hwang, Su Hwan; Lee, Yu Jin; Jeong, Do-Un; Park, Kwang Suk

2016-01-01

Nocturnal hypoxemia, characterized by abnormally low oxygen saturation levels in arterial blood during sleep, is a significant feature of various pathological conditions. The oxygen desaturation index, commonly used to evaluate the nocturnal hypoxemia severity, is acquired using nocturnal pulse oximetry that requires the overnight wear of a pulse oximeter probe. This study aimed to suggest a method for the unconstrained estimation of the oxygen desaturation index. We hypothesized that the severity of nocturnal hypoxemia would be positively associated with cardiac sympathetic activation during sleep. Unconstrained heart rate variability monitoring was conducted using three different ballistocardiographic systems to assess cardiac sympathetic activity. Overnight polysomnographic and ballistocardiographic recording pairs were collected from the 20 non-nocturnal hypoxemia (oxygen desaturation index <5 events/h) subjects and the 76 nocturnal hypoxemia patients. Among the 96 recording pairs, 48 were used as training data and the remaining 48 as test data. The regression analysis, performed using the low-frequency component of heart rate variability, exhibited a root mean square error of 3.33 events/h between the estimates and the reference values of the oxygen desaturation index. The nocturnal hypoxemia diagnostic performance produced by our method was presented with an average accuracy of 96.5% at oxygen desaturation index cutoffs of ≥5, 15, and 30 events/h. Our method has the potential to serve as a complementary measure against the accidental slip-out of a pulse oximeter probe during nocturnal pulse oximetry. The independent application of our method could facilitate home-based long-term oxygen desaturation index monitoring. © 2016 S. Karger AG, Basel.

Comparative anatomy and evolution of the cardiac innervation in New World monkeys (Platyrrhini, e. Geoffroy, 1812).

PubMed

Kawashima, Tomokazu; Thorington, Richard W; Whatton, James F

2009-05-01

The morphology of the autonomic cardiac nervous system (ACNS) was examined in 24 sides of 12 New World monkeys (Platyrrhini) of all four families to document the morphology systematically and to study the evolutionary changes of the ACNS in this primate lineage. We report the following: (1) Although several trivial intra- and inter-specific variations are present, a family-dependent morphology of the ACNS does not exist in New World monkeys. (2) The sympathetic ganglia in New World monkeys consist of the superior cervical, the middle cervical, and the cervicothoracic which is composed of the inferior cervical and first and second thoracic, and the thoracic ganglia starting with the third thoracic. The general cardiac nervous system is the sympathetic middle and inferior cardiac nerves and all parasympathetic vagal cardiac branches. (3) The morphology of the ACNS in the New World monkeys is almost consistent regardless of the number of vertebrae, the cardiac position and deviation (axis), and the great arterial branching pattern of the aortic arch, and it is very similar to that in the Old World monkeys, with only one difference: the superior cervical ganglion in the New World monkeys tends to be relatively smaller, higher, and provides a narrower contribution to the spinal nerves than in the Old World monkeys. The ACNS morphology exhibits significant evolutionary changes within the primate lineage from New and Old World monkeys to humans. The comparative morphology within the lineage is concordant with the phylogeny, suggesting that the primate ACNS preserves its evolutionary history in close alignment with phylogeny.

Exaggerated coronary vasoconstriction limits muscle metaboreflex-induced increases in ventricular performance in hypertension

PubMed Central

Spranger, Marty D.; Kaur, Jasdeep; Sala-Mercado, Javier A.; Krishnan, Abhinav C.; Abu-Hamdah, Rania; Alvarez, Alberto; Machado, Tiago M.; Augustyniak, Robert A.

2017-01-01

Increases in myocardial oxygen consumption during exercise mainly occur via increases in coronary blood flow (CBF) as cardiac oxygen extraction is high even at rest. However, sympathetic coronary constrictor tone can limit increases in CBF. Increased sympathetic nerve activity (SNA) during exercise likely occurs via the action of and interaction among activation of skeletal muscle afferents, central command, and resetting of the arterial baroreflex. As SNA is heightened even at rest in subjects with hypertension (HTN), we tested whether HTN causes exaggerated coronary vasoconstriction in canines during mild treadmill exercise with muscle metaboreflex activation (MMA; elicited by reducing hindlimb blood flow by ~60%) thereby limiting increases in CBF and ventricular performance. Experiments were repeated after α1-adrenergic blockade (prazosin; 75 µg/kg) and in the same animals following induction of HTN (modified Goldblatt 2K1C model). HTN increased mean arterial pressure from 97.1 ± 2.6 to 132.1 ± 5.6 mmHg at rest and MMA-induced increases in CBF, left ventricular dP/dtmax, and cardiac output were markedly reduced to only 32 ± 13, 26 ± 11, and 28 ± 12% of the changes observed in control. In HTN, α1-adrenergic blockade restored the coronary vasodilation and increased in ventricular function to the levels observed when normotensive. We conclude that exaggerated MMA-induced increases in SNA functionally vasoconstrict the coronary vasculature impairing increases in CBF, which limits oxygen delivery and ventricular performance in HTN. NEW & NOTEWORTHY We found that metaboreflex-induced increases in coronary blood flow and ventricular contractility are attenuated in hypertension. α1-Adrenergic blockade restored these parameters toward normal levels. These findings indicate that the primary mechanism mediating impaired metaboreflex-induced increases in ventricular function in hypertension is accentuated coronary vasoconstriction. Listen to this article’s corresponding podcast at http://ajpheart.podbean.com/e/metaboreflex-induced-functional-coronary-vasoconstriction/. PMID:27769997

Renal Sympathetic Denervation for Treatment of Hypertension.

PubMed

Pimenta, Eduardo; Oparil, Suzanne

2012-02-01

OPINION STATEMENT: Sympathetic nervous system activation of the heart, kidney and peripheral vasculature increases cardiac output, fluid retention and vascular resistance and plays an important role in acute and chronic BP elevation. Renal sympathetic denervation via a percutaneous radiofrequency catheter based approach is a safe and effective procedure that lowers BP in patients with resistant hypertension. Exploratory studies in patients with resistant hypertension and a variety of comorbidities, including insulin resistance/metabolic syndrome, obstructive sleep apnea and the polycystic ovary syndrome, have shown benefit of renal denervation in attenuating the severity of the comorbid conditions, as well as reducing BP. However, more studies are needed to further address the long term effects of renal denervation and its safety and effectiveness in other disease states such as congestive heart failure.

Electrocardiographic Characteristics of Potential Organ Donors and Associations with Cardiac Allograft Utilization

PubMed Central

Khush, Kiran K.; Menza, Rebecca; Nguyen, John; Goldstein, Benjamin A.; Zaroff, Jonathan G.; Drew, Barbara J.

2012-01-01

Background Current regulations require that all cardiac allograft offers for transplantation must include an interpreted 12-lead electrocardiogram (ECG). However, little is known about the expected ECG findings in potential organ donors, or the clinical significance of any identified abnormalities in terms of cardiac allograft function and suitability for transplantation. Methods and Results A single experienced reviewer interpreted the first ECG obtained after brainstem herniation in 980 potential organ donors managed by the California Transplant Donor Network from 2002-2007. ECG abnormalities were summarized, and associations between specific ECG findings and cardiac allograft utilization for transplantation were studied. ECG abnormalities were present in 51% of all cases reviewed. The most common abnormalities included voltage criteria for left ventricular hypertrophy (LVH), prolongation of the corrected QT interval (QTc), and repolarization changes (ST/T wave abnormalities). Fifty seven percent of potential cardiac allografts in this cohort were accepted for transplantation. LVH on ECG was a strong predictor of allograft non-utilization. No significant associations were seen between QTc prolongation, repolarization changes and allograft utilization for transplantation, after adjusting for donor clinical variables and echocardiographic findings. Conclusions We have performed the first comprehensive study of ECG findings in potential donors for cardiac transplantation. Many of the common ECG abnormalities seen in organ donors may result from the heightened state of sympathetic activation that occurs after brainstem herniation, and are not associated with allograft utilization for transplantation. PMID:22615333

[Individual peculiarities of adaptation to long-term space flights: 24-hour heart rhythm monitoring

NASA Technical Reports Server (NTRS)

Baevskii, R. M.; Bogomolov, V. V.; Gol'dberger, A. L.; Nikulina, G. A.; Charl'z, D. B.; Goldberger, A. L. (Principal Investigator); Charles, J. B. (Principal Investigator)

2000-01-01

Presented are results of studying 24-hr variability of the cardiac rhythm which characterizes individual difference in reactions of two crew members to the same set of stresses during a 115-day MIR mission. Spacelab (USA) cardiorecorders were used. Data of monitoring revealed significantly different baseline health statuses of the cosmonauts. These functional differences were also observed in the mission. In one of the cosmonauts, the cardiac regulation changed over to a more economic functioning with the autonomous balance shifted towards enhanced sympathetic activity. After 2-3 months on mission he had almost recovered pre-launch level of regulation. In the other, the regulatory system was appreciably strained at the beginning of the mission as compared with preflight baseline. Later on, on flight months 2-3, this strain kept growing till a drastic depletion of the functional reserve. On return to Earth, this was manifested by a strong stress reaction with a sharp decline in power of high-frequency and grow in power of very low frequency components of the heart rhythm. The data suggest that adaptation to space flight and reactions in the readaptation period are dependent on initial health status of crew members, and functional reserve.

RNA Sequencing Reveals Novel Transcripts from Sympathetic Stellate Ganglia During Cardiac Sympathetic Hyperactivity.

PubMed

Bardsley, Emma N; Davis, Harvey; Ajijola, Olujimi A; Buckler, Keith J; Ardell, Jeffrey L; Shivkumar, Kalyanam; Paterson, David J

2018-06-05

Cardiovascular disease is the most prevalent age-related illness worldwide, causing approximately 15 million deaths every year. Hypertension is central in determining cardiovascular risk and is a strong predictive indicator of morbidity and mortality; however, there remains an unmet clinical need for disease-modifying and prophylactic interventions. Enhanced sympathetic activity is a well-established contributor to the pathophysiology of hypertension, however the cellular and molecular changes that increase sympathetic neurotransmission are not known. The aim of this study was to identify key changes in the transcriptome in normotensive and spontaneously hypertensive rats. We validated 15 of our top-scoring genes using qRT-PCR, and network and enrichment analyses suggest that glutamatergic signalling plays a key role in modulating Ca 2+ balance within these ganglia. Additionally, phosphodiesterase activity was found to be altered in stellates obtained from the hypertensive rat, suggesting that impaired cyclic nucleotide signalling may contribute to disturbed Ca 2+ homeostasis and sympathetic hyperactivity in hypertension. We have also confirmed the presence of these transcripts in human donor stellate samples, suggesting that key genes coupled to neurotransmission are conserved. The data described here may provide novel targets for future interventions aimed at treating sympathetic hyperactivity associated with cardiovascular disease and other dysautonomias.

Detailed comparative anatomy of the extrinsic cardiac nerve plexus and postnatal reorganization of the cardiac position and innervation in the great apes: orangutans, gorillas, and chimpanzees.

PubMed

Kawashima, Tomokazu; Sato, Fumi

2012-03-01

To speculate how the extrinsic cardiac nerve plexus (ECNP) evolves phyletically and ontogenetically within the primate lineage, we conducted a comparative anatomical study of the ECNP, including an imaging examination in the great apes using 20 sides from 11 bodies from three species and a range of postnatal stages from newborns to mature adults. Although the position of the middle cervical ganglion (MG) in the great apes tended to be relatively lower than that in humans, the morphology of the ECNP in adult great apes was almost consistent with that in adult humans but essentially different from that in the lesser apes or gibbons. Therefore, the well-argued anatomical question of when did the MG acquire communicating branches with the spinal cervical nerves and appear constantly in all sympathetic cardiac nerves during primate evolution is clearly considered to be after the great apes and gibbons split. Moreover, a horizontal four-chambered heart and a lifted cardiac apex with a relatively large volume in newborn great apes rapidly changed its position downward, as seen in humans during postnatal growth and was associated with a reduction in the hepatic volume by imaging diagnosis and gross anatomy. In addition, our observation using a range of postnatal stages exhibits that two sympathetic ganglia, the middle cervical and cervicothoracic ganglia, differed between the early and later postnatal stages. Copyright © 2011 Wiley Periodicals, Inc.

Sleep and autonomic nervous system changes - enhanced cardiac sympathetic modulations during sleep in permanent night shift nurses.

PubMed

Chung, Min-Huey; Kuo, Terry B J; Hsu, Nanly; Chu, Hsin; Chou, Kuei-Ru; Yang, Cheryl C H

2009-05-01

Disturbed sleep is the most common problem among the many health-related effects of shift work, with shift workers clearly having higher rates of cardiac disorders. However, the possible mechanism underlying the related health effects of shift work has yet to be examined. Consequently, this study aimed to explore the influence of long-term night shift work on the sleep patterns of nurses and their cardiac autonomic nervous system during sleep. Our sample comprised ten permanent night shift and ten regular morning shift nurses. Nurses slept in their dormitory where they were allowed to sleep and wake spontaneously. All sleep parameters were digitized using an ambulatory polysomnographic recorder. Using sleep patterns and heart rate variability, the day- and nighttime sleep of permanent night shift nurses were compared with the nighttime sleep of regular morning shift nurses. Compared with the nighttime sleep of regular morning shift nurses, the pattern of daytime sleep of permanent night shift nurses showed significantly lower sleep onset latency. Permanent night shift nurses' daytime sleep also had greater proportions of Stage 3 and 4 (deep sleep), and arousal index than recorded during their nighttime sleep. Both the low frequency and low to high frequency ratio of the nighttime sleep of night shift nurses were significantly higher during periods of non-rapid eye movement (NREM) sleep than the nighttime sleep of morning shift workers. In addition, the electroencephalography delta-power of the nighttime sleep of night shift nurses was significantly lower during the first NREM episode sleep than those of both the daytime sleep of night shift workers and the nighttime sleep of morning shift nurses. Permanent night shift nurses have higher sympathetic activity during nighttime sleep than regular morning shift nurses. Night shift working may have effects on the sleeping patterns of nurses in the long run, inducing higher cardiac sympathetic regulation.

The effects of different physical activities on atrial fibrillation in patients with hypertension and chronic kidney disease

PubMed Central

Kiuchi, Márcio Galindo; Chen, Shaojie; Hoye, Neil Alexander

2017-01-01

Background Atrial fibrillation (AF) is highly common, and is most frequently observed in individuals with hypertension and structural cardiac disease. Sympathetic hyperactivity plays a fundamental role in the progression, maintenance and aggravation of arrhythmia. Endurance exercise training clearly lowers sympathetic activity in sympathoexcitatory disease states, and is well-tolerated by patients with chronic kidney disease (CKD). Methods We assessed 50 CKD patients with hypertension. Each patient provided a complete medical history and underwent a physical examination. We used an implantable cardiac monitor over a 3-year follow-up period to evaluate the effects of high-intensity interval training (HIIT) and moderate exercise (ModEx) physical activity protocols on AF occurrence, and determined the effectiveness of these protocols in improving renal function. Subjects were followed up every 6 months after the beginning of the intervention. Results During the 3-year follow-up, AF onset was higher in CKD patients who engaged in HIIT (72%) than in those who engaged in ModEx (24%) (hazard ratio, 3.847; 95% confidence interval, 1.694–8.740, P = 0.0013 by log-rank test). Both groups exhibited significant intra-group changes in the mean systolic 24-hour ambulatory blood pressure measurements (ABPM) between baseline and 12, 24, and 36 months. There were also significant differences in the mean systolic 24-hour ABPM between the groups at the same time points. Conclusion In CKD patients with hypertension, improvements in AF onset, renal function and some echocardiographic parameters were more evident in subjects who engaged in ModEx than in those who engaged in HIIT during 3 years of follow-up. PMID:28904878

Children's patterns of emotional reactivity to conflict as explanatory mechanisms in links between interpartner aggression and child physiological functioning.

PubMed

Davies, Patrick T; Sturge-Apple, Melissa L; Cicchetti, Dante; Manning, Liviah G; Zale, Emily

2009-11-01

This paper examined children's fearful, sad, and angry reactivity to interparental conflict as mediators of associations between their exposure to interparental aggression and physiological functioning. Participants included 200 toddlers and their mothers. Assessments of interparental aggression and children's emotional reactivity were derived from maternal surveys and a semi-structured interview. Cortisol levels and cardiac indices of sympathetic nervous system (SNS) and parasympathetic nervous system (PNS) activity were used to assess toddler physiological functioning. Results indicated that toddler exposure to interparental aggression was associated with greater cortisol levels and PNS activity and diminished SNS activity. Toddler angry emotional reactivity mediated associations between interparental aggression and cortisol and PNS functioning. Fearful emotional reactivity was a mediator of the link between interparental aggression and SNS functioning. The results are interpreted within conceptualizations of how exposure and reactivity to family risk organize individual differences in physiological functioning.

Impact of Leucine Supplementation on Exercise Training Induced Anti-Cardiac Remodeling Effect in Heart Failure Mice

PubMed Central

de Moraes, Wilson Max Almeida Monteiro; Melara, Thaís Plasti; de Souza, Pamella Ramona Moraes; de Salvi Guimarães, Fabiana; Bozi, Luiz Henrique Marchesi; Brum, Patricia Chakur; Medeiros, Alessandra

2015-01-01

Leucine supplementation potentiates the effects of aerobic exercise training (AET) on skeletal muscle; however, its potential effects associated with AET on cardiac muscle have not been clarified yet. We tested whether leucine supplementation would potentiate the anti-cardiac remodeling effect of AET in a genetic model of sympathetic hyperactivity-induced heart failure in mice (α2A/α2CARKO). Mice were assigned to five groups: wild type mice treated with placebo and sedentary (WT, n = 11), α2A/α2CARKO treated with placebo and sedentary (KO, n = 9), α2A/α2CARKO treated with leucine and sedentary (KOL, n = 11), α2A/α2CARKO treated with placebo and AET (KOT, n = 12) or α2A/α2CARKO treated with leucine and AET (KOLT, n = 12). AET consisted of four weeks on a treadmill with 60 min sessions (six days/week, 60% of maximal speed) and administration by gavage of leucine (1.35 g/kg/day) or placebo (distilled water). The AET significantly improved exercise capacity, fractional shortening and re-established cardiomyocytes’ diameter and collagen fraction in KOT. Additionally, AET significantly prevented the proteasome hyperactivity, increased misfolded proteins and HSP27 expression. Isolated leucine supplementation displayed no effect on cardiac function and structure (KOL), however, when associated with AET (KOLT), it increased exercise tolerance to a higher degree than isolated AET (KOT) despite no additional effects on AET induced anti-cardiac remodeling. Our results provide evidence for the modest impact of leucine supplementation on cardiac structure and function in exercised heart failure mice. Leucine supplementation potentiated AET effects on exercise tolerance, which might be related to its recognized impact on skeletal muscle. PMID:25988767

Cerebellar Ataxia, Seizures, Premature Death, and Cardiac Abnormalities in Mice with Targeted Disruption of the Cacna2d2 Gene

PubMed Central

Ivanov, Sergey V.; Ward, Jerrold M.; Tessarollo, Lino; McAreavey, Dorothea; Sachdev, Vandana; Fananapazir, Lameh; Banks, Melissa K.; Morris, Nicole; Djurickovic, Draginja; Devor-Henneman, Deborah E.; Wei, Ming-Hui; Alvord, Gregory W.; Gao, Boning; Richardson, James A.; Minna, John D.; Rogawski, Michael A.; Lerman, Michael I.

2004-01-01

CACNA2D2 is a putative tumor suppressor gene located in the human chromosome 3p21.3 region that shows frequent allelic imbalances in lung, breast, and other cancers. The α2δ-2 protein encoded by the gene is a regulatory subunit of voltage-dependent calcium channels and is expressed in brain, heart, and other tissues. Here we report that mice homozygous for targeted disruption of the Cacna2d2 gene exhibit growth retardation, reduced life span, ataxic gait with apoptosis of cerebellar granule cells followed by Purkinje cell depletion, enhanced susceptibility to seizures, and cardiac abnormalities. The Cacna2d2tm1NCIF null phenotype has much in common with that of Cacna1a mutants, such as cerebellar neuro-degeneration associated with ataxia, seizures, and premature death. A tendency to bradycardia and limited response of null mutants to isoflurane implicate α2δ-2 in sympathetic regulation of cardiac function. In summary, our findings provide genetic evidence that the α2δ-2 subunit serves in vivo as a component of P/Q-type calcium channels, is indispensable for the central nervous system function, and may be involved in hereditary cerebellar ataxias and epileptic disorders in humans. PMID:15331424

Sleep in heart failure.

PubMed

Naughton, Matthew T; Lorenzi-Filho, Geraldo

2009-01-01

Sleep plays a large role in patients with heart failure. In normal subjects, sleep is usually in a supine position with reduced sympathetic drive, elevated vagal tone and as such a relatively lower cardiac output and minute ventilation, allowing for recuperation. Patients with heart failure may not experience the same degree of autonomic activity change and the supine position may place a large strain on the pulmonary system. More than half of all heart failure patients have one of two types of sleep apnea: either obstructive or central sleep apnea. Some patients have both types. Obstructive sleep apnea is likely to be a cause of heart failure due to large negative intrathoracic pressures, apnea related hypoxemia and hypercapnia, terminated by an arousal and surge in systemic blood pressure associated with endothelial damage and resultant premature atherosclerosis. Reversal of obstructive sleep apnea improves blood pressure, systolic contraction and autonomic dysfunction however mortality studies are lacking. Central sleep apnea with Cheyne Stokes pattern of respiration (CSA-CSR) occurs as a result of increased central controller (brainstem driving ventilation) and plant (ventilation driving CO2) gain in the setting of a delayed feed back (i.e., low cardiac output). It is thought this type of apnea is a result of moderately to severely impaired cardiac function and is possibly indicative of high mortality. Treatment of CSA-CSR is best undertaken by treating the underlying cardiac condition which may include with medications, pacemakers, transplantation or continuous positive airway pressure (CPAP). In such patients CPAP exerts unique effects to assist cardiac function and reduce pulmonary edema. Whether CPAP improves survival in this heart failure population remains to be determined.

Proof of concept study: renal sympathetic denervation for treatment of polymorphic premature ventricular complexes.

PubMed

Kiuchi, Márcio Galindo; E Silva, Gustavo Ramalho; Paz, Luis Marcelo Rodrigues; Chen, Shaojie; Souto, Gladyston Luiz Lima

2016-11-01

Polymorphic premature ventricular complexes (PVCs) are very common, appearing most frequently in patients with hypertension, obesity, sleep apnea, and structural heart disease. Sympathetic hyperactivity plays a critical role in the development, maintenance, and aggravation of ventricular arrhythmias. Recently, the relevance of sympathetic activation in patients with ventricular arrhythmias was reported, and this finding suggested a potential role for catheter-based renal sympathetic denervation in reducing the arrhythmic burden. We evaluated the effectiveness of the renal sympathetic denervation (RSD) in comparison to antiarrhythmic pharmacologic therapy in reducing polymorphic PVCs refractory to medication therapy and cardiac parameters assessed by 24-h Holter monitoring and cardiac magnetic resonance (CRM), respectively, in patients with structurally normal heart. Thirty-four patients were included in this study, 14 served as control, and 20 were treated with an ablation cardiac catheter with open irrigated tip. RSD was performed by a single operator following the standard technique. All the patients included had polymorphic PVCs and structurally normal heart. Data were obtained at baseline at the 12th month of follow-up (sixth month after RSD or adjustment of antiarrhythmic dosage). In RSD group, we observed a significant decrease in the number of polymorphic PVCs from baseline 36,091 ± 3327 to 3, 6, 7 (first month after RSD, without drugs), and 12 months (sixth month after RSD, without drugs) of follow-up, 31,009 ± 3251, 20,411 ± 3820, 7701 ± 1549, and 1274 ± 749, respectively, in all patients, P < 0.0001 to all the comparisons between the mean of each time point with the mean of every other time point. No changes in mean 24-h ABPM and renal function in both groups were observed at 12th month of follow-up. However, 24-h Holter mean heart rate decreased in control group at 12th month of follow-up, which did not happen with the RSD group. At the sixth month post-RSD in comparison to baseline, a significant reduction in the number of polymorphic PVCs (∆ = -34,817 ± 3590, P < 0.0001) was observed, as well as, in CRM parameters such as left ventricular mass/body surface area (∆ = -5.4 ± 2.1 g/m 2 , P < 0.0001) and left ventricular ejection fraction (∆ = +3.0 ± 1.8 %, P < 0.0001). In comparison to control group at the same time point, these findings were statistically superior in RSD group (P > 0.05). A significant correlation was found between the Δ number of polymorphic PVCs at the sixth month (r = -0.6723, P = 0.0012) after the RSD and the total number of RSD ablated spots. Polymorphic PVCs refractory to medication therapy may be modifiable by RSD in patients without structural heart disease. Although encouraging, our data are preliminary and need to be validated in a large population and in long term.

Sympathetic activity induced by naloxone-precipitated morphine withdrawal is blocked in genetically engineered mice lacking functional CRF1 receptor

DOE Office of Scientific and Technical Information (OSTI.GOV)

García-Carmona, Juan-Antonio; Martínez-Laorden, Elena; Milanés, María-Victoria

There is large body evidence indicating that stress can lead to cardiovascular disease. However, the exact brain areas and the mechanisms involved remain to be revealed. Here, we performed a series of experiments to characterize the role of CRF1 receptor (CRF1R) in the stress response induced by naloxone-precipitated morphine withdrawal. The experiments were performed in the hypothalamic paraventricular nucleus (PVN) ventrolateral medulla (VLM), brain regions involved in the regulation of cardiovascular activity, and in the right ventricle by using genetically engineered mice lacking functional CRF1R levels (KO). Mice were treated with increasing doses of morphine and withdrawal was precipitated bymore » naloxone administration. Noradrenaline (NA) turnover, c-Fos, expression, PKA and TH phosphorylated at serine 40, was evaluated by high-performance liquid chromatography (HPLC), immunohistochemistry and immunoblotting. Morphine withdrawal induced an enhancement of NA turnover in PVN in parallel with an increase in TH neurons expressing c-Fos in VLM in wild-type mice. In addition we have demonstrated an increase in NA turnover, TH phosphorylated at serine 40 and PKA levels in heart. The main finding of the present study was that NA turnover, TH positive neurons that express c-Fos, TH phosphorylated at serine 40 and PKA expression observed during morphine withdrawal were significantly inhibited in CRF1R KO mice. Our results demonstrate that CRF/CRF1R activation may contribute to the adaptive changes induced by naloxone-precipitated withdrawal in the heart and in the brain areas which modulate the cardiac sympathetic function and suggest that CRF/CRF1R pathways could be contributing to cardiovascular disease associated to opioid addiction. - Highlights: • Naloxone-precipitated morphine withdrawal increases sympathetic activity in the PVN and heart. • Co-localization of TH phosphorylated at serine 40/c-Fos in the VLM after morphine withdrawal • Naloxone-precipitated morphine withdrawal increases PKA expression in the heart. • CRF1 receptor is implicated in the sympathetic activity induced by morphine withdrawal.« less

Association between obesity and heart rate variability indices: an intuition toward cardiac autonomic alteration - a risk of CVD.

PubMed

Yadav, Ram Lochan; Yadav, Prakash Kumar; Yadav, Laxmi Kumari; Agrawal, Kopila; Sah, Santosh Kumar; Islam, Md Nazrul

2017-01-01

Obese people have a higher prevalence of cardiovascular disease, which is supposed to be due to autonomic dysfunction and/or metabolic disorder. The alterations in cardiac autonomic functions bring out the changes in the heart rate variability (HRV) indicators, an assessing tool for cardiac autonomic conditions. To compare the cardiac autonomic activity between obese and normal weight adults and find out the highest association between the indices of HRV and obesity. The study was conducted in 30 adult obese persons (body mass index [BMI] >30 kg/m 2 ) and 29 healthy normal weight controls (BMI 18-24 kg/m 2 ). Short-term HRV variables were assessed using standard protocol. Data were compared between groups using Mann-Whitney U test. Obesity indices such as waist circumference, hip circumference, waist-hip ratio (WHR), and BMI were measured and calculated, and they were correlated with HRV indices using Spearman's correlation analysis. In the obese group, there was a significant increase in the mean heart rate, whereas the HRV parasympathetic indicators were less (eg, root mean square of differences of successive RR intervals [28.75 {16.72-38.35} vs 41.55 {30.6-56.75} ms, p =0.018], number of RR intervals that differ by >50 ms, that is, NN50 [15.5 {2-39} vs 83.5 {32.75-116.25}, p =0.010], etc) and the sympathetic indicator low frequency (LF)/high frequency (HF) ratio (1.2 [0.65-2.20] vs 0.79 [0.5-1.02], p =0.045) was more than that of the normal weight group. Spearman's correlation between HRV and obesity indices showed significant positive correlation of WHR with LF in normalized unit ( r =0.478, p <0.01) and LF/HF ratio ( r =0.479, p <0.01), whereas it had significant negative correlation with high frequency power ms 2 ( r =-0.374, p <0.05) and HF in normalized unit ( r =-0.478, p <0.01). There was a nonsignificant correlation of BMI with HRV variables in obese individuals. Increased WHR, by far an indicator of visceral adiposity, was strongly associated with reduced cardiac parasympathetic and increased sympathetic activity in obese individuals defined by BMI. However, BMI itself has a weak relationship with HRV cardiac autonomic markers. Thus, even with a slight increase in WHR in an individual, there could be a greater risk of cardiovascular morbidity and mortality brought about by cardiac autonomic alterations.

Chronic 5-HT2 receptor blockade unmasks the role of 5-HT1F receptors in the inhibition of rat cardioaccelerator sympathetic outflow.

PubMed

García-Pedraza, José Ángel; Hernández-Abreu, Oswaldo; García, Mónica; Morán, Asunción; Villalón, Carlos M

2018-04-01

Serotonin (5-hydroxytryptamine; 5-HT) inhibits the rat cardioaccelerator sympathetic outflow by 5-HT 1B/1D/5 receptors. Because chronic blockade of sympatho-excitatory 5-HT 2 receptors is beneficial in several cardiovascular pathologies, this study investigated whether sarpogrelate (a 5-HT 2 receptor antagonist) alters the pharmacological profile of the above sympatho-inhibition. Rats were pretreated for 2 weeks with sarpogrelate in drinking water (30 mg/kg per day; sarpogrelate-treated group) or equivalent volumes of drinking water (control group). Animals were pithed and prepared for spinal stimulation (C 7 -T 1 ) of the cardioaccelerator sympathetic outflow or for intravenous (i.v.) bolus injections of noradrenaline. Both procedures produced tachycardic responses remaining unaltered after saline. Continuous i.v. infusions of 5-HT induced a cardiac sympatho-inhibition that was mimicked by the 5-HT receptor agonists 5-carboxamidotryptamine (5-CT; 5-HT 1/5A ), CP 93,129 (5-HT 1B ), or PNU 142633 (5-HT 1D ), but not by indorenate (5-HT 1A ) in both groups; whereas LY344864 (5-HT 1F ) mimicked 5-HT only in sarpogrelate-treated rats. In sarpogrelate-treated animals, i.v. GR 127935 (310 μg/kg; 5-HT 1B/1D/1F receptor antagonist) attenuated 5-CT-induced sympatho-inhibition and abolished LY344864-induced sympatho-inhibition; while GR 127935 plus SB 699551 (1 mg/kg; 5-HT 5A receptor antagonist) abolished 5-CT-induced inhibition. These results confirm the cardiac sympatho-inhibitory role of 5-HT 1B , 5-HT 1D , and 5-HT 5A receptors in both groups; nevertheless, sarpogrelate treatment specifically unmasked a cardiac sympatho-inhibition mediated by 5-HT 1F receptors.

Autonomic cardiac regulation during spontaneous nocturnal hypoglycemia in patients with type 1 diabetes.

PubMed

Koivikko, Minna L; Tulppo, Mikko P; Kiviniemi, Antti M; Kallio, Mika A; Perkiömäki, Juha S; Salmela, Pasi I; Airaksinen, K E Juhani; Huikuri, Heikki V

2012-07-01

Experimental clamp studies have suggested that hypoglycemia evokes a reduction of cardiac vagal control in patients with type 1 diabetes. However, there are limited data on the influence of spontaneous nocturnal hypoglycemia on cardiac autonomic regulation. Adults with type 1 diabetes (n = 37) underwent continuous glucose monitoring via a subcutaneous sensor as well as recording of R-R interval or electrocardiogram for 3 nights. Heart rate (HR) variability was analyzed during periods of hypoglycemia (glucose <3.5 mmol/L) (minimum length of 20 min) and a control nonhypoglycemic period (glucose >3.9 mmol/L) of equal duration and at the same time of night. The duration of hypoglycemic and control episodes (n = 18) ranged from 20 to 190 min (mean 71 min). HR (62 ± 7 vs. 63 ± 9 beats per min; P = 0.30) or the high-frequency component of HR power spectrum (2,002 ± 1,965 vs. 1,336 ± 1,506 ms(2); P = 0.26) did not change during hypoglycemia. Hypoglycemia resulted in a significant decrease in the low-frequency component of HR variability (2,134 ± 1,635 vs. 1,169 ± 1,029 ms(2), respectively; P = 0.006). The decline in the glucose concentration displayed a significant positive correlation with the decrease of the low-frequency component of HR variability (r = 0.48; P = 0.04). The latter was closely related to an increase in muscle sympathetic nerve activity recorded in 10 subjects during controlled sympathetic activation. Spontaneous nocturnal hypoglycemia in patients with type 1 diabetes results in a reduction of the low-frequency component of HR, which is best explained by excessive sympathetic activation without a concomitant withdrawal of vagal outflow.

Role of N-type calcium channels in autonomic neurotransmission in guineapig isolated left atria

PubMed Central

Serone, Adrian P; Angus, James A

1999-01-01

Calcium entry via neuronal calcium channels is essential for the process of neurotransmission. We investigated the calcium channel subtypes involved in the operation of cardiac autonomic neurotransmission by examining the effects of selective calcium channel blockers on the inotropic responses to electrical field stimulation (EFS) of driven (4 Hz) guineapig isolated left atria. In this tissue, a previous report (Hong & Chang, 1995) found no evidence for N-type channels involved in the vagal negative inotropic response and only weak involvement in sympathetic responses. The effects of cumulative concentrations of the selective N-type calcium channel blocker, ω-conotoxin GVIA (GVIA; 0.1–10 nM) and the nonselective N-, P/Q-type calcium channel blocker, ω-conotoxin MVIIC (MVIIC; 0.01–10 nM) were examined on the positive (with atropine, 1 μM present) and negative (with propranolol, 1 μM and clonidine, 1 μM present) inotropic responses to EFS (eight trains, each train four pulses per punctate stimulus). GVIA caused complete inhibition of both cardiac vagal and sympathetic inotropic responses to EFS. GVIA was equipotent at inhibiting positive (pIC50 9.29±0.08) and negative (pIC50 9.13±0.17) inotropic responses. MVIIC also mediated complete inhibition of inotropic responses to EFS and was 160 and 85 fold less potent than GVIA at inhibiting positive (pIC50 7.08±0.10) and negative (pIC50 7.20±0.14) inotropic responses, respectively. MVIIC was also equipotent at inhibiting both sympathetic and vagal responses. Our data demonstrates that N-type calcium channels account for all the calcium current required for cardiac autonomic neurotransmission in the guinea-pig isolated left atrium. PMID:10433500

Independent prognostic importance of respiratory instability and sympathetic nerve activity in patients with chronic heart failure.

PubMed

Asanoi, Hidetsugu; Harada, Daisuke; Oda, Yoshitaka; Ueno, Hiroshi; Takagawa, Junya; Ishise, Hisanari; Goso, Yukiko; Joho, Shuji; Inoue, Hiroshi

2017-11-01

Respiratory instability in chronic heart failure (CHF) is characterized by irregularly rapid respiration or non-periodic breathing rather than by Cheyne-Stokes respiration. We developed a new quantitative measure of respiratory instability (RSI) and examined its independent prognostic impact upon CHF. In 87 patients with stable CHF, respiratory flow and muscle sympathetic nerve activity (MSNA) were simultaneously recorded. RSI was calculated from the frequency distribution of respiratory spectral components and very low frequency components. During a mean follow-up of 85±38 months, 24 patients died. Sixteen patients who died of cardiac causes had a lower RSI (16±6 vs. 30±21, p<0.01), a lower specific activity scale (4.3±1.4 Mets vs. 5.7±1.4 Mets, p<0.005), a higher MSNA burst area (16±5% vs. 11±4%, p<0.001), and a higher brain natriuretic peptide (BNP) level (514±559pg/ml vs. 234±311pg/ml, p<0.05) than 71 patients who did not die of cardiac causes. Multivariate analysis revealed that RSI (p=0.015), followed by MSNA burst area (p=0.033), was an independent predictor of subsequent all-cause deaths and that RSI (p=0.026), MSNA burst area (p=0.001), and BNP (p=0.048) were independent predictors of cardiac deaths. Patients at very high risk of fatal outcome could be identified by an RSI<20. The daytime respiratory instability quantified by a new measure of RSI has prognostic importance independent of sympathetic nerve activation in patients with clinically stable CHF. An RSI of <20 identifies patients at very high risk for subsequent all-cause and cardiovascular death. Copyright © 2017. Published by Elsevier Ltd.

Favorable effects of carotid endarterectomy on baroreflex sensitivity and cardiovascular neural modulation: a 4-month follow-up.

PubMed

Dalla Vecchia, Laura; Barbic, Franca; Galli, Andrea; Pisacreta, Massimo; Gornati, Rosella; Porretta, Tiziano; Porta, Alberto; Furlan, Raffaello

2013-06-15

Carotid surgery variably modifies carotid afferent innervation, thus affecting arterial baroreceptor sensitivity. Low arterial baroreflex sensitivity is a well-known independent risk factor for cardiovascular diseases. The aim of this study was to assess the 4-mo effects of carotid endarterectomy (CEA) on arterial baroreceptor sensitivity and cardiovascular autonomic profile in patients with unilateral carotid stenosis. We enrolled 20 patients (72 ± 8 yr) with unilateral >70% carotid stenosis. ECG, beat-by-beat blood pressure, and respiration were continuously recorded before and 126 ± 9 days after CEA, at rest and during a 75° head-up tilt. Both pharmacological (modified Oxford technique, BRS) and spontaneous (index α, spectral analysis) arterial baroreflex sensitivity were assessed. Cardiovascular autonomic profile was evaluated by plasma catecholamines and spectral indexes of cardiac sympathovagal modulation [low-frequency R-R interval (LFRR), low frequency-to high frequency ratio (LF/HF), high-frequency R-R interval (HFRR)] and sympathetic vasomotor control [low-frequency systolic arterial pressure (LFSAP)] obtained from heart rate and SAP variability. After CEA, both the index α and BRS were higher (P < 0.02) at rest. SAP variance decreased both at rest and during tilt (P < 0.02). Before surgery, tilt did not modify the autonomic profile compared with baseline. After CEA, tilt increased LF/HF and LFSAP and reduced HFRR compared with rest (P < 0.02). Four months after CEA was performed, arterial baroreflex sensitivity was enhanced. Accordingly, the patients' autonomic profile had shifted toward reduced cardiac and vascular sympathetic activation and enhanced cardiac vagal activity. The capability to increase cardiovascular sympathetic activation in response to orthostasis was restored. Baroreceptor sensitivity improvement might play an additional role in the more favorable outcome observed in patients after carotid surgery.

elPBN neurons regulate rVLM activity through elPBN-rVLM projections during activation of cardiac sympathetic afferent nerves

PubMed Central

Longhurst, John C.; Tjen-A-Looi, Stephanie C.; Fu, Liang-Wu

2016-01-01

The external lateral parabrachial nucleus (elPBN) within the pons and rostral ventrolateral medulla (rVLM) contributes to central processing of excitatory cardiovascular reflexes during stimulation of cardiac sympathetic afferent nerves (CSAN). However, the importance of elPBN cardiovascular neurons in regulation of rVLM activity during CSAN activation remains unclear. We hypothesized that CSAN stimulation excites the elPBN cardiovascular neurons and, in turn, increases rVLM activity through elPBN-rVLM projections. Compared with controls, in rats subjected to microinjection of retrograde tracer into the rVLM, the numbers of elPBN neurons double-labeled with c-Fos (an immediate early gene) and the tracer were increased after CSAN stimulation (P < 0.05). The majority of these elPBN neurons contain vesicular glutamate transporter 3. In cats, epicardial bradykinin and electrical stimulation of CSAN increased the activity of elPBN cardiovascular neurons, which was attenuated (n = 6, P < 0.05) after blockade of glutamate receptors with iontophoresis of kynurenic acid (Kyn, 25 mM). In separate cats, microinjection of Kyn (1.25 nmol/50 nl) into the elPBN reduced rVLM activity evoked by both bradykinin and electrical stimulation (n = 5, P < 0.05). Excitation of the elPBN with microinjection of dl-homocysteic acid (2 nmol/50 nl) significantly increased basal and CSAN-evoked rVLM activity. However, the enhanced rVLM activity induced by dl-homocysteic acid injected into the elPBN was reversed following iontophoresis of Kyn into the rVLM (n = 7, P < 0.05). These data suggest that cardiac sympathetic afferent stimulation activates cardiovascular neurons in the elPBN and rVLM sequentially through a monosynaptic (glutamatergic) excitatory elPBN-rVLM pathway. PMID:27225950

Bradykinin activates a cross-signaling pathway between sensory and adrenergic nerve endings in the heart: a novel mechanism of ischemic norepinephrine release?

PubMed

Seyedi, N; Maruyama, R; Levi, R

1999-08-01

We had shown that bradykinin (BK) generated by cardiac sympathetic nerve endings (i.e., synaptosomes) promotes exocytotic norepinephrine (NE) release in an autocrine mode. Because the synaptosomal preparation may include sensory C-fiber endings, which BK is known to stimulate, sensory nerves could contribute to the proadrenergic effects of BK in the heart. We report that BK is a potent releaser of NE from guinea pig heart synaptosomes (EC(50) approximately 20 nM), an effect mediated by B(2) receptors, and almost completely abolished by prior C-fiber destruction or blockade of calcitonin gene-related peptide and neurokinin-1 receptors. C-fiber destruction also greatly decreased BK-induced NE release from the intact heart, whereas tyramine-induced NE release was unaffected. Furthermore, C-fiber stimulation with capsaicin and activation of calcitonin gene-related peptide and neurokinin-1 receptors initiated NE release from cardiac synaptosomes, indicating that stimulation of sensory neurons in turn activates sympathetic nerve terminals. Thus, BK is likely to release NE in the heart in part by first liberating calcitonin gene-related peptide and Substance P from sensory nerve endings; these neuropeptides then stimulate specific receptors on sympathetic terminals. This action of BK is positively modulated by cyclooxygenase products, attenuated by activation of histamine H(3) receptors, and potentiated at a lower pH. The NE-releasing action of BK is likely to be enhanced in myocardial ischemia, when protons accumulate, C fibers become activated, and the production of prostaglandins and BK increases. Because NE is a major arrhythmogenic agent, the activation of this interneuronal signaling system between sensory and adrenergic neurons may contribute to ischemic dysrhythmias and sudden cardiac death.

The Association between Baseline Subjective Anxiety Rating and Changes in Cardiac Autonomic Nervous Activity in Response to Tryptophan Depletion in Healthy Volunteers

PubMed Central

Hsiao, Chih Yin; Tsai, Hsin Chun; Chi, Mei Hung; Chen, Kao Chin; Chen, Po See; Lee, I Hui; Yeh, Tzung Lieh; Yang, Yen Kuang

2016-01-01

Abstract The aim of this study was to investigate the influence of serotonin on anxiety and autonomic nervous system (ANS) function; the correlation between subjective anxiety rating and changes of ANS function following tryptophan depletion (TD) in healthy volunteers was examined. Twenty-eight healthy participants, consisting of 15 females and 13 males, with an average age of 33.3 years, were recruited. Baseline Chinese Symptom Checklist-90-Revised and ANS function measurements were taken. TD was carried out on the testing day, and participants provided blood samples right before and 5 hours after TD. ANS function, somatic symptoms, and Visual Analogue Scales (VASs) were determined after TD. Wilcoxon signed rank test and Spearman ρ correlation were adapted for analyses of the results. The TD procedure reduced total and free plasma tryptophan effectively. After TD, the sympathetic nervous activity increased and parasympathetic nervous activity decreased. Baseline anxiety ratings positively correlated with post-TD changes in sympathetic nervous activity, VAS ratings, and physical symptoms. However, a negative correlation with post-TD changes in parasympathetic nervous activity was found. The change in ANS function after TD was associated with the severity of anxiety in healthy volunteers. This supports the fact that the effect of anxiety on heart rate variability is related to serotonin vulnerability. Furthermore, it also shows that the subjective anxiety rating has a biological basis related to serotonin. PMID:27175645

The Association between Baseline Subjective Anxiety Rating and Changes in Cardiac Autonomic Nervous Activity in Response to Tryptophan Depletion in Healthy Volunteers.

PubMed

Hsiao, Chih Yin; Tsai, Hsin Chun; Chi, Mei Hung; Chen, Kao Chin; Chen, Po See; Lee, I Hui; Yeh, Tzung Lieh; Yang, Yen Kuang

2016-05-01

The aim of this study was to investigate the influence of serotonin on anxiety and autonomic nervous system (ANS) function; the correlation between subjective anxiety rating and changes of ANS function following tryptophan depletion (TD) in healthy volunteers was examined. Twenty-eight healthy participants, consisting of 15 females and 13 males, with an average age of 33.3 years, were recruited.Baseline Chinese Symptom Checklist-90-Revised and ANS function measurements were taken. TD was carried out on the testing day, and participants provided blood samples right before and 5 hours after TD. ANS function, somatic symptoms, and Visual Analogue Scales (VASs) were determined after TD. Wilcoxon signed rank test and Spearman ρ correlation were adapted for analyses of the results.The TD procedure reduced total and free plasma tryptophan effectively. After TD, the sympathetic nervous activity increased and parasympathetic nervous activity decreased. Baseline anxiety ratings positively correlated with post-TD changes in sympathetic nervous activity, VAS ratings, and physical symptoms. However, a negative correlation with post-TD changes in parasympathetic nervous activity was found.The change in ANS function after TD was associated with the severity of anxiety in healthy volunteers. This supports the fact that the effect of anxiety on heart rate variability is related to serotonin vulnerability. Furthermore, it also shows that the subjective anxiety rating has a biological basis related to serotonin.

Cardiorespiratory Coupling: Common Rhythms in Cardiac, Sympathetic, and Respiratory Activities

PubMed Central

Dick, Thomas E.; Hsieh, Yee-Hsee; Dhingra, Rishi R.; Baekey, David M.; Galán, Roberto F.; Wehrwein, Erica; Morris, Kendall F.

2014-01-01

Cardiorespiratory coupling is an encompassing term describing more than the well-recognized influences of respiration on heart rate and blood pressure. Our data indicate that cardiorespiratory coupling reflects a reciprocal interaction between autonomic and respiratory control systems, and the cardiovascular system modulates the ventilatory pattern as well. For example, cardioventilatory coupling refers to the influence of heart beats and arterial pulse pressure on respiration and is the tendency for the next inspiration to start at a preferred latency after the last heart beat in expiration. Multiple complementary, well-described mechanisms mediate respiration’s influence on cardiovascular function, whereas mechanisms mediating the cardiovascular system’s influence on respiration may only be through the baroreceptors but are just being identified. Our review will describe a differential effect of conditioning rats with either chronic intermittent or sustained hypoxia on sympathetic nerve activity but also on ventilatory pattern variability. Both intermittent and sustained hypoxia increase sympathetic nerve activity after 2 weeks but affect sympatho-respiratory coupling differentially. Intermittent hypoxia enhances sympatho-respiratory coupling, which is associated with low variability in the ventilatory pattern. In contrast, after constant hypobaric hypoxia, 1-to-1 coupling between bursts of sympathetic and phrenic nerve activity is replaced by 2-to-3 coupling. This change in coupling pattern is associated with increased variability of the ventilatory pattern. After baro-denervating hypobaric hypoxic-conditioned rats, splanchnic sympathetic nerve activity becomes tonic (distinct bursts are absent) with decreases during phrenic nerve bursts and ventilatory pattern becomes regular. Thus, conditioning rats to either intermittent or sustained hypoxia accentuates the reciprocal nature of cardiorespiratory coupling. Finally, identifying a compelling physiologic purpose for cardiorespiratory coupling is the biggest barrier for recognizing its significance. Cardiorespiratory coupling has only a small effect on the efficiency of gas exchange; rather, we propose that cardiorespiratory control system may act as weakly coupled oscillator to maintain rhythms within a bounded variability. PMID:24746049

Dynamic analysis of patterns of renal sympathetic nerve activity: implications for renal function.

PubMed

DiBona, Gerald F

2005-03-01

Methods of dynamic analysis are used to provide additional understanding of the renal sympathetic neural control of renal function. The concept of functionally specific subgroups of renal sympathetic nerve fibres conveying information encoded in the frequency domain is presented. Analog pulse modulation and pseudorandom binary sequence stimulation patterns are used for the determination of renal vascular frequency response. Transfer function analysis is used to determine the effects of non-renal vasoconstrictor and vasoconstrictor intensities of renal sympathetic nerve activity on dynamic autoregulation of renal blood flow.

Baroreceptors mask sympathetic responses to high intraocular pressure in dogs.

PubMed

Yahagi, Toru; Koyama, Shozo; Osaka, Kazumasa; Koyama, Haruhide

2008-05-30

These experiments were designed to investigate whether increasing intraocular pressure (IOP) in anesthetized dogs produces differential control of sympathetic nerve activities to various organs (heart, kidney, liver, and spleen) and if these sympathetic responses are modified by baroreceptors. We performed simultaneous multi-recordings of cardiac, renal, hepatic and splenic sympathetic nerve activities (CNA, RNA, HNA and SpNA, respectively) during 2 min of increasing IOP to a mean pressure of 30 mmHg. After increasing IOP in dogs with the intact baroreceptors, all of measured nerve activities did not change significantly throughout the experiment. In dogs with denervation of baroreceptors (cervical vagotomy with denervation of the carotid sinus and aortic nerves), only RNA and CNA showed significant increases in response to the increased IOP. However, time course changes in HNA and SpNA did not show any significant differences as compared with the baseline or that of the control group. These results indicate that systemic sympathetic nerve responses to increasing IOP are masked by systemic baroreceptors. As animals were denervated of their systemic baroreceptors, the unidirectional sympathoexcitatory responses to increased IOP were observed on CNA and RNA, but not on HNA and SpNA. These sympathetic outflow, when systemic baroreceptors are impaired as observed in old age, may play an important role in management of glaucoma attack with the use of adrenolytic drugs.

Substrate metabolism, hormone interaction, and angiotensin-converting enzyme inhibitors in left ventricular hypertrophy.

PubMed

Zhu, Y C; Zhu, Y Z; Spitznagel, H; Gohlke, P; Unger, T

1996-01-01

Left ventricular hypertrophy is considered to be an independent risk factor giving rise to ischemia, arrhythmias, and left ventricular dysfunction. Slow movement of intracellular calcium contributes to the impaired contraction and relaxation function of hypertrophied myocardium. Myofibril content may also be shifted to fetal-type isoforms with decreased contraction and relaxation properties in left ventricular hypertrophy. Myocyte hypertrophy and interstitial fibrosis are regulated independently by mechanical and neurohumoral mechanisms. In severely hypertrophied myocardium, capillary density is reduced, the diffusion distance for oxygen, nutrients, and metabolites is increased, and the ratio of energy-production sites to energy-consumption sites is decreased. The metabolic state of severely hypertrophied myocardium is anaerobic, as indicated by the shift of lactate dehydrogenase marker enzymes. Therefore, the hypertrophied myocardium is more vulnerable to ischemic events. As a compensatory response to severe cardiac hypertrophy and congestive heart failure, the ADP/ATP carrier is activated and atrial natriuretic peptide is released to increase high-energy phosphate production and reduce cardiac energy consumption by vasodilation and sodium and fluid elimination. However, in severely hypertrophied and failing myocardium, vasoconstrictor and sodium- and fluid-retaining factors, such as the renin-angiotensin system, aldosterone, and sympathetic nerve activity, play an overwhelming role. Angiotensin-converting enzyme inhibitors (ACEIs) are able to prevent cardiac hypertrophy and improve cardiac function and metabolism. Under experimental conditions, these beneficial effects can be ascribed mainly to bradykinin potentiation, although a contribution of the ACEI-induced angiotensin II reduction cannot be excluded.

Combined short-arm centrifuge and aerobic exercise training improves cardiovascular function and physical working capacity in humans.

PubMed

Yang, Chang-Bin; Zhang, Shu; Zhang, Yu; Wang, Bing; Yao, Yong-Jie; Wang, Yong-Chun; Wu, Yan-Hong; Liang, Wen-Bin; Sun, Xi-Qing

2010-12-01

Musculoskeletal and cardiovascular deconditioning occurring in long-term spaceflight gives rise to the needs to develop new strategies to counteract these adverse effects. Short-arm centrifuge combined with ergometer has been proposed as a strategy to counteract adverse effects of microgravity. This study sought to investigate whether the combination of short-arm centrifuge and aerobic exercise training have advantages over short-arm centrifuge or aerobic exercise training alone. One week training was conducted by 24 healthy men. They were randomly divided into 3 groups: (1) short-arm centrifuge training, (2) aerobic exercise training, 40 W, and (3) combined short-arm centrifuge and aerobic exercise training. Before and after training, the cardiac pump function represented by stroke volume, cardiac output, left ventricular ejection time, and total peripheral resistance was evaluated. Variability of heart rate and systolic blood pressure were determined by spectral analysis. Physical working capacity was surveyed by near maximal physical working capacity test. The 1-week combined short-arm centrifuge and aerobic exercise training remarkably ameliorated the cardiac pump function and enhanced vasomotor sympathetic nerve modulation and improved physical working capacity by 10.9% (P<.05, n=8). In contrast, neither the short-arm centrifuge nor the aerobic exercise group showed improvements in these functions. These results demonstrate that combined short-arm centrifuge and aerobic exercise training has advantages over short-arm centrifuge or aerobic exercise training alone in influencing several physiologically important cardiovascular functions in humans. The combination of short-arm centrifuge and aerobic exercise offers a promising countermeasure to microgravity.

SYMPATHETIC NEURAL AND HEMODYNAMIC RESPONSES DURING COLD PRESSOR TEST IN ELDERLY BLACKS AND WHITES

PubMed Central

Okada, Yoshiyuki; Jarvis, Sara S.; Best, Stuart A.; Edwards, Jeffrey G.; Hendrix, Joseph M.; Adams-Huet, Beverley; Vongpatanasin, Wanpen; Levine, Benjamin D.; Fu, Qi

2016-01-01

The sympathetic response during the cold pressor test (CPT) has been reported to be greater in young blacks than whites, especially in those with a family history of hypertension. Since blood pressure (BP) increases with age, we evaluated whether elderly blacks have greater sympathetic activation during CPT than age-matched whites. BP, heart rate (HR), cardiac output (Qc), and muscle sympathetic nerve activity (MSNA) were measured during supine baseline, 2-min CPT, and 3-min recovery in 47 elderly [68±7 (SD) yrs] volunteers (12 blacks, 35 whites). Baseline BP, HR, Qc, or MSNA did not differ between races. Systolic and diastolic BP (DBP) and HR increased during CPT (all P<0.001) with no racial differences (all P>0.05). Qc increased during CPT and up to 30 sec of recovery in both groups, but was lower in blacks than whites. MSNA increased during CPT in both groups (both P<0.001); the increase in burst frequency was similar between groups, while the increase in total activity was smaller in blacks (P=0.030 for interaction). Peak change (Δ) in DBP was correlated with Δ total activity at 1 min into CPT in both blacks (r=0.78, P=0.003) and whites (r=0.43, P=0.009), while the slope was significantly greater in blacks (P=0.007). Thus, elderly blacks have smaller sympathetic and central hemodynamic (e.g., Qc) responses, but a greater pressor response for a given sympathetic activation during CPT than elderly whites. This response may stem from augmented sympathetic vascular transduction, greater sympathetic activation to other vascular bed(s), and/or enhanced non-adrenergically mediated vasoconstriction in elderly blacks. PMID:27021009

Assessing the strength of cardiac and sympathetic baroreflex controls via transfer entropy during orthostatic challenge

NASA Astrophysics Data System (ADS)

Porta, Alberto; Marchi, Andrea; Bari, Vlasta; De Maria, Beatrice; Esler, Murray; Lambert, Elisabeth; Baumert, Mathias

2017-05-01

The study assesses the strength of the causal relation along baroreflex (BR) in humans during an incremental postural challenge soliciting the BR. Both cardiac BR (cBR) and sympathetic BR (sBR) were characterized via BR sequence approaches from spontaneous fluctuations of heart period (HP), systolic arterial pressure (SAP), diastolic arterial pressure (DAP) and muscle sympathetic nerve activity (MSNA). A model-based transfer entropy method was applied to quantify the strength of the coupling from SAP to HP and from DAP to MSNA. The confounding influences of respiration were accounted for. Twelve young healthy subjects (20-36 years, nine females) were sequentially tilted at 0°, 20°, 30° and 40°. We found that (i) the strength of the causal relation along the cBR increases with tilt table inclination, while that along the sBR is unrelated to it; (ii) the strength of the causal coupling is unrelated to the gain of the relation; (iii) transfer entropy indexes are significantly and positively associated with simplified causality indexes derived from BR sequence analysis. The study proves that causality indexes are complementary to traditional characterization of the BR and suggests that simple markers derived from BR sequence analysis might be fruitfully exploited to estimate causality along the BR. This article is part of the themed issue `Mathematical methods in medicine: neuroscience, cardiology and pathology'.

Acupuncture's Cardiovascular Actions: A Mechanistic Perspective.

PubMed

Longhurst, John

2013-04-01

Over the last several decades, there has been an explosion of articles on acupuncture, including studies that have begun to explore mechanisms underlying its analgesic and cardiovascular actions. Modulation of cardiovascular function is most effective during manual and low-frequency, low-intensity electroacupuncture (EA) at a select set of acupoints situated along meridians located over deep somatic nerves on the upper and lower extremities. Stimulation at these acupoints activates underlying sensory neural pathways that project to a number of regions in the central nervous system (CNS) that ultimately regulate autonomic outflow and hence cardiovascular function. A long-loop pathway involving the hypothalamus, midbrain, and medulla underlies EA modulation of reflex increases in blood pressure (BP). Actions of excitatory and inhibitory neurotransmitters in the supraspinal CNS underlie processing of the somatic input and adjustment of autonomic outflow during EA. Acupuncture also decreases elevated blood pressure through actions in the thoracic spinal cord. Reflexes that lower BP likewise are modulated by EA through its actions on sympathetic and parasympathetic nuclei in the medulla. The autonomic influence of acupuncture is slow in onset but prolonged in duration, typically lasting beyond the period of stimulation. Clinical studies suggest that acupuncture can be used to treat cardiac diseases, such as myocardial ischemia and hypertension, associated with overactivity of the sympathetic nervous system.

Acupuncture's Cardiovascular Actions: A Mechanistic Perspective

PubMed Central

2013-01-01

Abstract Over the last several decades, there has been an explosion of articles on acupuncture, including studies that have begun to explore mechanisms underlying its analgesic and cardiovascular actions. Modulation of cardiovascular function is most effective during manual and low-frequency, low-intensity electroacupuncture (EA) at a select set of acupoints situated along meridians located over deep somatic nerves on the upper and lower extremities. Stimulation at these acupoints activates underlying sensory neural pathways that project to a number of regions in the central nervous system (CNS) that ultimately regulate autonomic outflow and hence cardiovascular function. A long-loop pathway involving the hypothalamus, midbrain, and medulla underlies EA modulation of reflex increases in blood pressure (BP). Actions of excitatory and inhibitory neurotransmitters in the supraspinal CNS underlie processing of the somatic input and adjustment of autonomic outflow during EA. Acupuncture also decreases elevated blood pressure through actions in the thoracic spinal cord. Reflexes that lower BP likewise are modulated by EA through its actions on sympathetic and parasympathetic nuclei in the medulla. The autonomic influence of acupuncture is slow in onset but prolonged in duration, typically lasting beyond the period of stimulation. Clinical studies suggest that acupuncture can be used to treat cardiac diseases, such as myocardial ischemia and hypertension, associated with overactivity of the sympathetic nervous system. PMID:24761168

Acute effects of MDMA on autonomic cardiac activity and their relation to subjective prosocial and stimulant effects.

PubMed

Clark, Christine M; Frye, Charles G; Wardle, Margaret C; Norman, Greg J; de Wit, Harriet

2015-03-01

MDMA is a stimulant with unique "prosocial" effects, the physiological and pharmacological mechanisms of which are unknown. Here, we examine the relationship of measures of parasympathetic and sympathetic nervous system activity to the prosocial effects of MDMA. Parasympathetic activity was measured using respiratory sinus arrhythmia (RSA) and sympathetic activity using pre-ejection period (PEP). Over three sessions, 33 healthy volunteers received placebo, 0.75 mg/kg, and 1.5 mg/kg MDMA under counterbalanced, double-blind conditions, while we measured subjective feelings, RSA, and PEP. RSA and PEP data were available for 26 and 21 participants, respectively. MDMA increased prosocial and stimulated feelings, decreased RSA, and decreased PEP. At 1.5 mg/kg, subjective prosocial effects correlated with stimulated feelings and PEP, but not RSA. This suggests sympathetic, rather than parasympathetic, effects relate to the prosocial effects of MDMA. © 2014 Society for Psychophysiological Research.

Central fat influences cardiac autonomic function in obese and overweight girls.

PubMed

Soares-Miranda, Luisa; Alves, Alberto J; Vale, Susana; Aires, Luisa; Santos, Rute; Oliveira, José; Mota, Jorge

2011-10-01

It has been suggested that upper-body fat compared with lower-body fat is more closely associated with cardiovascular abnormalities. Our objective was to analyze the relationship between central fat (CF) and cardiac autonomic (cANS) function in obese and overweight girls. Children were classified in two groups based on CF: those above (CFa(50)) and those below the 50th percentile (CFb(50)) of the entire sample. This study included 16 female children who were diagnosed as being overweight or obese (age: 14.3 ± 2.8 years; weight: 75.0 ± 15.8 kg; height: 157.1 ± 8.9 cm; body mass index: 30.1 ± 5.4; and total body fat: 40.5 ± 5.0%; Tanner stage: 4). cANS function was assessed through heart rate variability (HRV) and CF parameters by dual-energy X-ray absorptiometry. Female children with higher CF exhibited significantly higher sympathetic and lower parasympathetic modulation than those with lower CF, independently of total body fat. The data of the present study indicate that CF is associated with less favorable indexes of HRV. In addition, our findings suggest that CF might be an important measure to assess the effect of obesity on cANS function in female children.

Beat-to-beat blood pressure analysis after premature ventricular contraction indicates sensitive baroreceptor dysfunction in Parkinson's disease.

PubMed

Haensch, Carl-Albrecht; Jörg, Johannes

2006-04-01

Extrasystoles occur in normal subjects but are significant more frequently (16.25% vs. 55%; chi(2) = 19.3; P < 0.001) seen in Parkinson's disease (PD) patients. The extrasystolic decreases in stroke volume and systolic pressure activate sympathetic vasomotor innervation and lead to a blood pressure increase for a few heartbeats. The purpose of this study was to prove whether the short time analysis of this blood pressure regulation allows the assessment of sympathetic neurocirculatory function. Records of noninvasive blood pressure monitoring were reviewed from 40 PD patients and 80 controls. A battery of cardiovascular autonomic tests, including Valsalva maneuver, tilt-table testing, echocardiography, and cardiac scintigraphy with [(123)I]meta-iodobenzylguanidine were performed. Fifty-five percent of the PD patients had at least one premature ventricular contraction (PVC) in 10 minutes lying supine at rest. After every PVC (13 PVCs) recorded from normal subjects, we found an increase in systolic blood pressure above base line with a maximum at the seventh heart beat. In all of the 22 PD patients, the systolic blood pressure was significantly decreased less than baseline in every PVC from the second to the ninth postextrasystolic beat (P < 0.001). In both groups, the extrasystolic fall in blood pressure was on average approximately 22%. The postextrasystolic potentiation did not differ (5.3% vs. 4.4%, not significant). If a PVC occurs, the analysis of short-time blood pressure regulation is a sensitive tool for baroreceptor reflex function. The advantage of this method results from the independence of patients cooperation and the high sensitivity to prove a sympathetic neurocirculatory failure within 10 heart beats. Copyright 2005 Movement Disorder Society.

Asymmetry in the control of cardiac performance by dorsomedial hypothalamus.

PubMed

Xavier, Carlos Henrique; Beig, Mirza Irfan; Ianzer, Danielle; Fontes, Marco Antônio Peliky; Nalivaiko, Eugene

2013-04-15

Dorsomedial hypothalamus (DMH) plays a key role in integrating cardiovascular responses to stress. We have recently reported greater heart rate responses following disinhibition of the right side of the DMH (R-DMH) in anesthetized rats and greater suppression of stress-induced tachycardia following inhibition of the R-DMH in conscious rats [both compared with similar intervention in the left DMH (L-DMH)], suggesting existence of right/left side asymmetry in controlling cardiac chronotropic responses by the DMH. The aim of the present study was to determine whether similar asymmetry is present for controlling cardiac contractility. In anesthetized rats, microinjections of the GABAA antagonist bicuculline methiodide (BMI; 40 pmol/100 nl) into the DMH-evoked increases in heart rate (HR), left ventricular pressure (LVP), myocardial contractility (LVdP/dt), arterial pressure, and respiratory rate. DMH disinhibition also precipitated multiple ventricular and supraventricular ectopic beats. DMH-induced increases in HR, LVP, LVdP/dt, and in the number of ectopic beats dependent on the side of stimulation, with R-DMH provoking larger responses. In contrast, pressor and respiratory responses did not depend on the side of stimulation. Newly described DMH-induced inotropic responses were rate-, preload- and (largely) afterload-independent; they were mediated by sympathetic cardiac pathway, as revealed by their sensitivity to β-adrenergic blockade. We conclude that recruitment of DMH neurons causes sympathetically mediated positive chronotropic and inotropic effects, and that there is an asymmetry, at the level of the DMH, in the potency to elicit these effects, with R-DMH > L-DMH.

Investigation following resuscitated cardiac arrest.

PubMed

Skinner, Jonathan R

2013-01-01

Roughly two thirds of resuscitated cardiac arrests in children and youth are due to inherited heart diseases. The most commonly implicated are the cardiac ion channelopathies long QT syndrome, CPVT (catecholaminergic polymorphic ventricular tachycardia) and Brugada syndrome. Diagnosis is pivotal to further management of the child if he/she survives, and also to other family members who may be at risk. Thorough investigation of the cardiac arrest survivor is essential to either identify or exclude inherited heart disease. If standard cardiac investigation does not reveal a diagnosis, pharmacological provocation tests are needed to unmask electrocardiographic signs of disease, even if, due to severe brain injury, it is planned ultimately to allow a natural death. Examples are the ajmaline/flecainide challenge for Brugada syndrome and epinephrine for CPVT. A supportive, informative and sympathetic approach to the family is essential. An arrhythmia specialist and a cardiac genetic service should be involved early, with storage of DNA and cardiac/genetic investigation of the family. This review proposes a diagnostic algorithm-based approach to the investigation of this increasingly common clinical scenario.

Developmental androgen excess programs sympathetic tone and adipose tissue dysfunction and predisposes to a cardiometabolic syndrome in female mice.

PubMed

Nohara, Kazunari; Waraich, Rizwana S; Liu, Suhuan; Ferron, Mathieu; Waget, Aurélie; Meyers, Matthew S; Karsenty, Gérard; Burcelin, Rémy; Mauvais-Jarvis, Franck

2013-06-15

Among women, the polycystic ovarian syndrome (PCOS) is considered a form of metabolic syndrome with reproductive abnormalities. Women with PCOS show increased sympathetic tone, visceral adiposity with enlarged adipocytes, hypoadiponectinemia, insulin resistance, glucose intolerance, increased inactive osteocalcin, and hypertension. Excess fetal exposure to androgens has been hypothesized to play a role in the pathogenesis of PCOS. Previously, we showed that neonatal exposure to the androgen testosterone (NT) programs leptin resistance in adult female mice. Here, we studied the impact of NT on lean and adipose tissues, sympathetic tone in cardiometabolic tissues, and the development of metabolic dysfunction in mice. Neonatally androgenized adult female mice (NTF) displayed masculinization of lean tissues with increased cardiac and skeletal muscle as well as kidney masses. NTF mice showed increased and dysfunctional white adipose tissue with increased sympathetic tone in both visceral and subcutaneous fat as well as increased number of enlarged and insulin-resistant adipocytes that displayed altered expression of developmental genes and hypoadiponectinemia. NTF exhibited dysfunctional brown adipose tissue with increased mass and decreased energy expenditure. They also displayed decreased undercarboxylated and active osteocalcin and were predisposed to obesity during chronic androgen excess. NTF showed increased renal sympathetic tone associated with increased blood pressure, and they developed glucose intolerance and insulin resistance. Thus, developmental exposure to testosterone in female mice programs features of cardiometabolic dysfunction, as can be observed in women with PCOS, including increased sympathetic tone, visceral adiposity, insulin resistance, prediabetes, and hypertension.

Developmental androgen excess programs sympathetic tone and adipose tissue dysfunction and predisposes to a cardiometabolic syndrome in female mice

PubMed Central

Nohara, Kazunari; Waraich, Rizwana S.; Liu, Suhuan; Ferron, Mathieu; Waget, Aurélie; Meyers, Matthew S.; Karsenty, Gérard; Burcelin, Rémy

2013-01-01

Among women, the polycystic ovarian syndrome (PCOS) is considered a form of metabolic syndrome with reproductive abnormalities. Women with PCOS show increased sympathetic tone, visceral adiposity with enlarged adipocytes, hypoadiponectinemia, insulin resistance, glucose intolerance, increased inactive osteocalcin, and hypertension. Excess fetal exposure to androgens has been hypothesized to play a role in the pathogenesis of PCOS. Previously, we showed that neonatal exposure to the androgen testosterone (NT) programs leptin resistance in adult female mice. Here, we studied the impact of NT on lean and adipose tissues, sympathetic tone in cardiometabolic tissues, and the development of metabolic dysfunction in mice. Neonatally androgenized adult female mice (NTF) displayed masculinization of lean tissues with increased cardiac and skeletal muscle as well as kidney masses. NTF mice showed increased and dysfunctional white adipose tissue with increased sympathetic tone in both visceral and subcutaneous fat as well as increased number of enlarged and insulin-resistant adipocytes that displayed altered expression of developmental genes and hypoadiponectinemia. NTF exhibited dysfunctional brown adipose tissue with increased mass and decreased energy expenditure. They also displayed decreased undercarboxylated and active osteocalcin and were predisposed to obesity during chronic androgen excess. NTF showed increased renal sympathetic tone associated with increased blood pressure, and they developed glucose intolerance and insulin resistance. Thus, developmental exposure to testosterone in female mice programs features of cardiometabolic dysfunction, as can be observed in women with PCOS, including increased sympathetic tone, visceral adiposity, insulin resistance, prediabetes, and hypertension. PMID:23612996

The Effects of Sympathetic Inhibition on Metabolic and Cardiopulmonary Responses to Exercise in Hypoxic Conditions.

PubMed

Scalzo, Rebecca L; Peltonen, Garrett L; Binns, Scott E; Klochak, Anna L; Szallar, Steve E; Wood, Lacey M; Larson, Dennis G; Luckasen, Gary J; Irwin, David; Schroeder, Thies; Hamilton, Karyn L; Bell, Christopher

2015-12-01

Pre-exertion skeletal muscle glycogen content is an important physiological determinant of endurance exercise performance: low glycogen stores contribute to premature fatigue. In low-oxygen environments (hypoxia), the important contribution of carbohydrates to endurance performance is further enhanced as glucose and glycogen dependence is increased; however, the insulin sensitivity of healthy adult humans is decreased. In light of this insulin resistance, maintaining skeletal muscle glycogen in hypoxia becomes difficult, and subsequent endurance performance is impaired. Sympathetic inhibition promotes insulin sensitivity in hypoxia but may impair hypoxic exercise performance, in part due to suppression of cardiac output. Accordingly, we tested the hypothesis that hypoxic exercise performance after intravenous glucose feeding in a low-oxygen environment will be attenuated when feeding occurs during sympathetic inhibition. On 2 separate occasions, while breathing a hypoxic gas mixture, 10 healthy men received 1 hour of parenteral carbohydrate infusion (20% glucose solution in saline; 75 g), after which they performed stationary cycle ergometer exercise (~65% maximal oxygen uptake) until exhaustion. Forty-eight hours before 1 visit, chosen randomly, sympathetic inhibition via transdermal clonidine (0.2 mg/d) was initiated. The mean time to exhaustion after glucose feeding both with and without sympathetic inhibition was not different (22.7 ± 5.4 minutes vs 23.5 ± 5.1 minutes; P = .73). Sympathetic inhibition protects against hypoxia-mediated insulin resistance without influencing subsequent hypoxic endurance performance. Copyright © 2015 Wilderness Medical Society. Published by Elsevier Inc. All rights reserved.

Baroreflex and neurovascular responses to skeletal muscle mechanoreflex activation in humans: an exercise in integrative physiology.

PubMed

Drew, Rachel C

2017-12-01

Cardiovascular adjustments to exercise resulting in increased blood pressure (BP) and heart rate (HR) occur in response to activation of several neural mechanisms: the exercise pressor reflex, central command, and the arterial baroreflex. Neural inputs from these feedback and feedforward mechanisms integrate in the cardiovascular control centers in the brain stem and modulate sympathetic and parasympathetic neural outflow, resulting in the increased BP and HR observed during exercise. Another specific consequence of the central neural integration of these inputs during exercise is increased sympathetic neural outflow directed to the kidneys, causing renal vasoconstriction, a key reflex mechanism involved in blood flow redistribution during increased skeletal muscle work. Studies in humans have shown that muscle mechanoreflex activation inhibits cardiac vagal outflow, decreasing the sensitivity of baroreflex control of HR. Metabolite sensitization of muscle mechanoreceptors can lead to reduced sensitivity of baroreflex control of HR, with thromboxane being one of the metabolites involved, via greater inhibition of cardiac vagal outflow without affecting baroreflex control of BP or baroreflex resetting. Muscle mechanoreflex activation appears to play a predominant role in causing renal vasoconstriction, both in isolation and in the presence of local metabolites. Limited investigations in older adults and patients with cardiovascular-related disease have provided some insight into how the influence of muscle mechanoreflex activation on baroreflex function and renal vasoconstriction is altered in these populations. However, future research is warranted to better elucidate the specific effect of muscle mechanoreflex activation on baroreflex and neurovascular responses with aging and cardiovascular-related disease. Copyright © 2017 the American Physiological Society.

Role of the autonomic nervous system and baroreflex in stress-evoked cardiovascular responses in rats.

PubMed

Dos Reis, Daniel Gustavo; Fortaleza, Eduardo Albino Trindade; Tavares, Rodrigo Fiacadori; Corrêa, Fernando Morgan Aguiar

2014-07-01

Restraint stress (RS) is an experimental model to study stress-related cardiovascular responses, characterized by sustained pressor and tachycardiac responses. We used pharmacologic and surgical procedures to investigate the role played by sympathetic nervous system (SNS) and parasympathetic nervous system (PSNS) in the mediation of stress-evoked cardiovascular responses. Ganglionic blockade with pentolinium significantly reduced RS-evoked pressor and tachycardiac responses. Intravenous treatment with homatropine methyl bromide did not affect the pressor response but increased tachycardia. Pretreatment with prazosin reduced the pressor and increased the tachycardiac response. Pretreatment with atenolol did not affect the pressor response but reduced tachycardia. The combined treatment with atenolol and prazosin reduced both pressor and tachycardiac responses. Adrenal demedullation reduced the pressor response without affecting tachycardia. Sinoaortic denervation increased pressor and tachycardiac responses. The results indicate that: (1) the RS-evoked cardiovascular response is mediated by the autonomic nervous system without an important involvement of humoral factors; (2) hypertension results primarily from sympathovascular and sympathoadrenal activation, without a significant involvement of the cardiac sympathetic component (CSNS); (3) the abrupt initial peak in the hypertensive response to restraint is sympathovascular-mediated, whereas the less intense but sustained hypertensive response observed throughout the remaining restraint session is mainly mediated by sympathoadrenal activation and epinephrine release; (4) tachycardia results from CSNS activation, and not from PSNS inhibition; (5) RS evokes simultaneous CSNS and PSNS activation, and heart rate changes are a vector of both influences; (6) the baroreflex is functional during restraint, and modulates both the vascular and cardiac responses to restraint.

Early Endothelial Bioactivity of Serum after Diesel Exhaust ...

EPA Pesticide Factsheets

Adverse cardiovascular effects of air pollution are often associated with a spike in systemic proinflammatory biomarkers, but causative linkage between circulating factors and deleterious outcomes following exposure remains elusive. Endothelial dysfunction is a consequence of systemic inflammation and precedes multiple cardiovascular pathologies. The purpose of this study was to examine the plausibility of serum-bound factors as initiators of an air pollution-induced pathologic sequelae beginning with endothelial injury, and later, cardiac dysfunction. We hypothesized that serum taken from diesel exhaust (DE)-exposed rats that develop cardiac dysfunction would alter aortic endothelial cell function in vitro. To assess cardiac function in vivo, left ventricular pressure (LVP) assessments were conducted in rats one day after a single 4 hour whole body exposure to 150 or 500 μg/m3 DE or filtered air. Rat aortic endothelial cells (RAEC) were then exposed to diluted serum (10%) collected 1 hour after exposure from a separate cohort of similarly exposed rats for measures of VCAM-1, cell viability, nitric oxide synthase (NOS) levels, and mRNA expression of key mediators of inflammation. Exposure of rats to 150 or 500 μg/m3 DE increased heart rate (HR) after exposure relative to rats exposed to filtered air, suggesting a shift towards increased sympathetic tone. LVP and HR in DE-exposed rats (500 μg/m3 DE) failed to recover to normal levels after challenge with the

Bitters: Time for a New Paradigm.

PubMed

McMullen, Michael K; Whitehouse, Julie M; Towell, Anthony

2015-01-01

In plant-based medical systems, bitter tasting plants play a key role in managing dyspepsia. Yet when it comes to defining their mechanism of activity, herbalists and pharmacologists are split between two theories: one involves cephalic elicited vagal responses while the other comprises purely local responses. Recent studies indicate that bitters elicit a range of cephalic responses which alter postprandial gastric phase haemodynamics. Caffeine and regular coffee (Coffea arabica semen, L.) increase heart rate whereas gentian (Gentiana lutea radix, L.) and wormwood (Artemisia absinthium herba L.) increase tonus in the vascular resistance vessels. Following meals increased cardiac activity acts to support postprandial hyperaemia and maintain systemic blood pressure. The increased vascular tonus acts in parallel with the increased cardiac activity and in normal adults this additional pressor effect results in a reduced cardiac workload. The vascular response is a sympathetic reflex, evident after 5 minutes and dose dependent. Thus gentian and wormwood elicit cephalic responses which facilitate rather than stimulate digestive activity when postprandial hyperaemia is inadequate. Encapsulated caffeine elicits cardiovascular responses indicating that gastrointestinal bitter receptors are functionally active in humans. However, neither encapsulated gentian nor wormwood elicited cardiovascular responses during the gastric phase. These findings provide the platform for a new evidence-based paradigm.

Bitters: Time for a New Paradigm

PubMed Central

McMullen, Michael K.; Whitehouse, Julie M.; Towell, Anthony

2015-01-01

In plant-based medical systems, bitter tasting plants play a key role in managing dyspepsia. Yet when it comes to defining their mechanism of activity, herbalists and pharmacologists are split between two theories: one involves cephalic elicited vagal responses while the other comprises purely local responses. Recent studies indicate that bitters elicit a range of cephalic responses which alter postprandial gastric phase haemodynamics. Caffeine and regular coffee (Coffea arabica semen, L.) increase heart rate whereas gentian (Gentiana lutea radix, L.) and wormwood (Artemisia absinthium herba L.) increase tonus in the vascular resistance vessels. Following meals increased cardiac activity acts to support postprandial hyperaemia and maintain systemic blood pressure. The increased vascular tonus acts in parallel with the increased cardiac activity and in normal adults this additional pressor effect results in a reduced cardiac workload. The vascular response is a sympathetic reflex, evident after 5 minutes and dose dependent. Thus gentian and wormwood elicit cephalic responses which facilitate rather than stimulate digestive activity when postprandial hyperaemia is inadequate. Encapsulated caffeine elicits cardiovascular responses indicating that gastrointestinal bitter receptors are functionally active in humans. However, neither encapsulated gentian nor wormwood elicited cardiovascular responses during the gastric phase. These findings provide the platform for a new evidence-based paradigm. PMID:26074998

Interval training based on ventilatory anaerobic threshold increases cardiac vagal modulation and decreases high-sensitivity c-reative protein: randomized clinical trial in coronary artery disease.

PubMed

Tamburus, Nayara Y; Paula, Roberta F L; Kunz, Vandeni C; César, Marcelo C; Moreno, Marlene A; da Silva, Ester

2015-01-01

Autonomic dysfunction and inflammatory activity are involved in the development and progression of coronary artery disease (CAD), and exercise training has been shown to confer a cardiovascular benefit. To evaluate the effects that interval training (IT) based on ventilatory anaerobic threshold (VAT) has on heart rate variability (HRV) and high-sensitivity C-reactive protein (hs-CRP) levels, as well as the relationship between both levels, in patients with CAD and/or cardiovascular risk factors (RF). Forty-two men (aged 57.88±6.20 years) were divided into two training groups, CAD-T (n= 12) and RF-T (n= 10), and two control groups, CAD-C (n= 10) and RF-C (n=10). Heart rate and RR intervals in the supine position, cardiopulmonary exercise tests, and hs-CRP levels were measured before and after IT. HRV was analyzed by spectral and symbolic analysis. The CAD-T and RF-T underwent a 16-week IT program of three weekly sessions at training intensities based on the VAT. In the RF-T, cardiac sympathetic modulation index and hs-CRP decreased (p<0.02), while cardiac parasympathetic modulation index increased (p<0.02). In the CAD-T, cardiac parasympathetic modulation index increased, while hs-CRP, systolic, and diastolic blood pressures decreased (p<0.02). Both control groups showed increase in hs-CRP parameters (p<0.02). There was a strong and significant association between parasympathetic and sympathetic modulations with hs-CRP. The IT program based on the VAT promoted a decrease in hs-CRP associated with improvement in cardiac autonomic modulation.

Children’s Patterns of Emotional Reactivity to Conflict as Explanatory Mechanisms in Links Between Interpartner Aggression and Child Physiological Functioning

PubMed Central

Davies, Patrick T.; Sturge-Apple, Melissa L.; Cicchetti, Dante; Manning, Liviah G.; Zale, Emily

2009-01-01

Background This paper examined children’s fearful, sad, and angry reactivity to interparental conflict as mediators of associations between their exposure to interparental aggression and physiological functioning. Methods Participants included 200 toddlers and their mothers. Assessments of interparental aggression and children’s emotional reactivity were derived from maternal surveys and a semi-structured interview. Cortisol levels and cardiac indices of sympathetic nervous system (SNS) and parasympathetic nervous system (PNS) activity were used to assess toddler physiological functioning. Results Results indicated that toddler exposure to interparental aggression was associated with greater cortisol levels and PNS activity and diminished SNS activity. Toddler angry emotional reactivity mediated associations between interparental aggression and cortisol and PNS functioning. Fearful emotional reactivity was a mediator of the link between interparental aggression and SNS functioning. Conclusions The results are interpreted within conceptualizations of how exposure and reactivity to family risk organizing individual differences in physiological functioning. PMID:19744183

Initial Experience with IV Ketamine Infusion for Treatment of Post Sternotomy Pain in a Patient with a Total Artificial Heart.

PubMed

Maher, Dermot P; Loyferman, Rusty; Yumul, Roya; Louy, Charles

2015-01-01

The implantation of total artificial hearts (TAH) via midline sternotomy for the treatment of severe biventricular cardiac dysfunction is associated with complex postoperative pain management. Ketamaine increases blood pressure by raising sympathetic outflow and cardiac output; however, ketamine is a direct vasodilator on isolated arterial tissues. In the setting of a TAH with a mechanically fixed cardiac output, a ketamine infusion for postoperative pain control has the potential to decrease blood pressure due to direct arterial vasodilation. We present the initial experience with a ketamine infusion in a patient with a TAH with minimal observed decreases in blood pressure and significantly improved postoperative pain.

Effect of atropine or atenolol on cardiovascular responses to novelty stress in freely-moving rats.

PubMed

van den Buuse, Maarten

2002-09-01

Cardiac hemodynamic mechanisms involved in cardiovascular responses to stress were studied in conscious, freely-moving female spontaneously hypertensive rats exposed for 15 min to an open-field. When pretreated with saline, the rats displayed a rapid rise in blood pressure, heart rate, aortic dP/dt and locomotor activity. In rats pretreated with 0.5 mg/kg of methylatropine, the tachycardia was slightly, but significantly reduced. In rats pretreated with 1 mg/kg of atenolol, the tachycardis and rise in dP/dt were markedly reduced. These data suggest that the cardiac responses to stress include predominantly cardiac sympathetic activation and a minor component of vagal withdrawal.

Postnatal Cardiac Autonomic Nervous Control in Pediatric Congenital Heart Disease

PubMed Central

Nederend, Ineke; Jongbloed, Monique R. M.; de Geus, Eco J. C.; Blom, Nico A.; ten Harkel, Arend D. J.

2016-01-01

Congenital heart disease is the most common congenital defect. During childhood, survival is generally good but, in adulthood, late complications are not uncommon. Abnormal autonomic control in children with congenital heart disease may contribute considerably to the pathophysiology of these long term sequelae. This narrative review of 34 studies aims to summarize current knowledge on function of the autonomic nervous system in children with a congenital heart defect. Large scale studies that measure both branches of the nervous system for prolonged periods of time in well-defined patient cohorts in various phases of childhood and adolescence are currently lacking. Pending such studies, there is not yet a good grasp on the extent and direction of sympathetic and parasympathetic autonomic function in pediatric congenital heart disease. Longitudinal studies in homogenous patient groups linking autonomic nervous system function and clinical outcome are warranted. PMID:29367565

Cardiac Autonomic Balance vs. Cardiac Regulatory Capacity

PubMed Central

Berntson, Gary G.; Norman, Greg J.; Hawkley, Louise C.; Cacioppo, John T.

2013-01-01

The concept of autonomic balance views autonomic states along a bipolar continuum from sympathetic (S) to parasympathetic (P) dominance, whereas regulatory capacity models emphasize overall autonomic flexibility as a marker of the capacity for regulation. These two concepts were evaluated for their utility in characterizing patterns of autonomic control. Measures of P (high frequency heart rate variability, HF) and S (pre-ejection period, PEP) cardiac control were obtained. A measure of cardiac autonomic balance (CAB) was derived as the difference in the normalized P index minus the S index, and a measure of cardiac autonomic regulation (CAR) was derived as the normalized P index plus the S index. Results reveal that CAR, but not CAB, was a significant predictor of the prior occurrence of a myocardial infarction, net of demographic and other variables, whereas CAB, but not CAR, was a significant predictor of concurrent diabetes. PMID:18282204

Circadian variation in the circulatory responses to exercise: relevance to the morning peaks in strokes and cardiac events

PubMed Central

2009-01-01

Sudden cardiac and cerebral events are most common in the morning. A fundamental question is whether these events are triggered by the increase in physical activity after waking, and/or a result of circadian variation in the responses of circulatory function to exercise. Although signaling pathways from the master circadian clock in the suprachiasmatic nuclei to sites of circulatory control are not yet understood, it is known that cerebral blood flow, autoregulation and cerebrovascular reactivity to changes in CO2 are impaired in the morning and, therefore, could explain the increased risk of cerebrovascular events. Blood pressure (BP) and the rate pressure product (RPP) show marked ‘morning surges’ when people are studied in free-living conditions, making the rupture of a fragile atherosclerotic plaque and sudden cardiac event more likely. Since cerebral autoregulation is reduced in the morning, this surge in BP may also exacerbate the risk of hemorrhagic and ischemic strokes in the presence of other acute and chronic risk factors. Increased sympathetic activity, decreased endothelial function, and increased platelet aggregability could also be important in explaining the morning peak in cardiac and cerebral events but how these factors respond to exercise at different times of day is unclear. Evidence is emerging that the exercise-related responses of BP and RPP are increased in the morning when prior sleep is controlled. We recommend that such ‘semi-constant routine’ protocols are employed to examine the relative influence of the body clock and exogenous factors on the 24-h variation in other circulatory factors. PMID:19826832

Effect of Acute Ozone Induced Airway Inflammation on Human Sympathetic Nerve Traffic: A Randomized, Placebo Controlled, Crossover Study

PubMed Central

Tank, Jens; Biller, Heike; Heusser, Karsten; Holz, Olaf; Diedrich, André; Framke, Theodor; Koch, Armin; Grosshennig, Anika; Koch, Wolfgang; Krug, Norbert; Jordan, Jens; Hohlfeld, Jens M.

2011-01-01

Background Ozone concentrations in ambient air are related to cardiopulmonary perturbations in the aging population. Increased central sympathetic nerve activity induced by local airway inflammation may be one possible mechanism. Methodology/Principal Findings To elucidate this issue further, we performed a randomized, double-blind, cross-over study, including 14 healthy subjects (3 females, age 22–47 years), who underwent a 3 h exposure with intermittent exercise to either ozone (250 ppb) or clean air. Induced sputum was collected 3 h after exposure. Nineteen to 22 hours after exposure, we recorded ECG, finger blood pressure, brachial blood pressure, respiration, cardiac output, and muscle sympathetic nerve activity (MSNA) at rest, during deep breathing, maximum-inspiratory breath hold, and a Valsalva maneuver. While the ozone exposure induced the expected airway inflammation, as indicated by a significant increase in sputum neutrophils, we did not detect a significant estimated treatment effect adjusted for period on cardiovascular measurements. Resting heart rate (clean air: 59±2, ozone 60±2 bpm), blood pressure (clean air: 121±3/71±2 mmHg; ozone: 121±2/71±2 mmHg), cardiac output (clean air: 7.42±0.29 mmHg; ozone: 7.98±0.60 l/min), and plasma norepinephrine levels (clean air: 213±21 pg/ml; ozone: 202±16 pg/ml), were similar on both study days. No difference of resting MSNA was observed between ozone and air exposure (air: 23±2, ozone: 23±2 bursts/min). Maximum MSNA obtained at the end of apnea (air: 44±4, ozone: 48±4 bursts/min) and during the phase II of the Valsalva maneuver (air: 64±5, ozone: 57±6 bursts/min) was similar. Conclusions/Significance Our study suggests that acute ozone-induced airway inflammation does not increase resting sympathetic nerve traffic in healthy subjects, an observation that is relevant for environmental health. However, we can not exclude that chronic airway inflammation may contribute to sympathetic activation. PMID:21494635

Heart and brain interaction in patients with heart failure: overview and proposal for a taxonomy. A position paper from the Study Group on Heart and Brain Interaction of the Heart Failure Association.

PubMed

Doehner, Wolfram; Ural, Dilek; Haeusler, Karl Georg; Čelutkienė, Jelena; Bestetti, Reinaldo; Cavusoglu, Yuksel; Peña-Duque, Marco A; Glavas, Duska; Iacoviello, Massimo; Laufs, Ulrich; Alvear, Ricardo Marmol; Mbakwem, Amam; Piepoli, Massimo F; Rosen, Stuart D; Tsivgoulis, Georgios; Vitale, Cristiana; Yilmaz, M Birhan; Anker, Stefan D; Filippatos, Gerasimos; Seferovic, Petar; Coats, Andrew J S; Ruschitzka, Frank

2018-02-01

Heart failure (HF) is a complex clinical syndrome with multiple interactions between the failing myocardium and cerebral (dys-)functions. Bi-directional feedback interactions between the heart and the brain are inherent in the pathophysiology of HF: (i) the impaired cardiac function affects cerebral structure and functional capacity, and (ii) neuronal signals impact on the cardiovascular continuum. These interactions contribute to the symptomatic presentation of HF patients and affect many co-morbidities of HF. Moreover, neuro-cardiac feedback signals significantly promote aggravation and further progression of HF and are causal in the poor prognosis of HF. The diversity and complexity of heart and brain interactions make it difficult to develop a comprehensive overview. In this paper a systematic approach is proposed to develop a comprehensive atlas of related conditions, signals and disease mechanisms of the interactions between the heart and the brain in HF. The proposed taxonomy is based on pathophysiological principles. Impaired perfusion of the brain may represent one major category, with acute (cardio-embolic) or chronic (haemodynamic failure) low perfusion being sub-categories with mostly different consequences (i.e. ischaemic stroke or cognitive impairment, respectively). Further categories include impairment of higher cortical function (mood, cognition), of brain stem function (sympathetic over-activation, neuro-cardiac reflexes). Treatment-related interactions could be categorized as medical, interventional and device-related interactions. Also interactions due to specific diseases are categorized. A methodical approach to categorize the interdependency of heart and brain may help to integrate individual research areas into an overall picture. © 2017 The Authors. European Journal of Heart Failure © 2017 European Society of Cardiology.

Carotid Body Ablation Abrogates Hypertension and Autonomic Alterations Induced by Intermittent Hypoxia in Rats.

PubMed

Del Rio, Rodrigo; Andrade, David C; Lucero, Claudia; Arias, Paulina; Iturriaga, Rodrigo

2016-08-01

Chronic intermittent hypoxia (CIH), the main feature of obstructive sleep apnea, enhances carotid body (CB) chemosensory responses to hypoxia and produces autonomic dysfunction, cardiac arrhythmias, and hypertension. We tested whether autonomic alterations, arrhythmogenesis, and the progression of hypertension induced by CIH depend on the enhanced CB chemosensory drive, by ablation of the CB chemoreceptors. Male Sprague-Dawley rats were exposed to control (Sham) conditions for 7 days and then to CIH (5% O2, 12/h 8 h/d) for a total of 28 days. At 21 days of CIH exposure, rats underwent bilateral CB ablation and then exposed to CIH for 7 additional days. Arterial blood pressure and ventilatory chemoreflex response to hypoxia were measured in conscious rats. In addition, cardiac autonomic imbalance, cardiac baroreflex gain, and arrhythmia score were assessed during the length of the experiments. In separate experimental series, we measured extracellular matrix remodeling content in cardiac atrial tissue and systemic oxidative stress. CIH induced hypertension, enhanced ventilatory response to hypoxia, induced autonomic imbalance toward sympathetic preponderance, reduced baroreflex gain, and increased arrhythmias and atrial fibrosis. CB ablation normalized blood pressure, reduced ventilatory response to hypoxia, and restored cardiac autonomic and baroreflex function. In addition, CB ablation reduced the number of arrhythmias, but not extracellular matrix remodeling or systemic oxidative stress, suggesting that reductions in arrhythmia incidence during CIH were related to normalization of cardiac autonomic balance. Present results show that autonomic alterations induced by CIH are critically dependent on the CB and support a main role for the CB in the CIH-induced hypertension. © 2016 American Heart Association, Inc.

A general enhancement of autonomic and cortisol responses during social evaluative threat.

PubMed

Bosch, Jos A; de Geus, Eco J C; Carroll, Douglas; Goedhart, Annebet D; Anane, Leila A; van Zanten, Jet J Veldhuizen; Helmerhorst, Eva J; Edwards, Kate M

2009-10-01

To examine the Social Self Preservation Theory, which predicts that stressors involving social evaluative threat (SET) characteristically activate the hypothalamic-pituitary-adrenal (HPA) axis. The idea that distinct psychosocial factors may underlie specific patterns of neuroendocrine stress responses has been a topic of recurrent debate. Sixty-one healthy university students (n = 31 females) performed a challenging speech task in one of three conditions that aimed to impose increasing levels of SET: performing the task alone (no social evaluation), with one evaluating observer, or with four evaluating observers. Indices of sympathetic (preejection period) and parasympathetic (heart rate variability) cardiac drive were obtained by impedance- and electrocardiography. Salivary cortisol was used to index HPA activity. Questionnaires assessed affective responses. Affective responses (shame/embarrassment, anxiety, negative affect, and self-esteem), cortisol, heart rate, sympathetic and parasympathetic activation all differentiated evaluative from nonevaluative task conditions (p < .001). The largest effect sizes were observed for cardiac autonomic responses. Physiological reactivity increased in parallel with increasing audience size (p < .001). An increase in cortisol was predicted by sympathetic activation during the task (p < .001), but not by affective responses. It would seem that SET determines the magnitude, rather than the pattern, of physiological activation. This potential to perturb broadly multiple physiological systems may help explain why social stress has been associated with a range of health outcomes. We propose a threshold-activation model as a physiological explanation for why engaging stressors, such as those involving social evaluation or uncontrollability, may seem to induce selectively cortisol release.

Cardiovascular and respiratory dynamics during normal and pathological sleep

NASA Astrophysics Data System (ADS)

Penzel, Thomas; Wessel, Niels; Riedl, Maik; Kantelhardt, Jan W.; Rostig, Sven; Glos, Martin; Suhrbier, Alexander; Malberg, Hagen; Fietze, Ingo

2007-03-01

Sleep is an active and regulated process with restorative functions for physical and mental conditions. Based on recordings of brain waves and the analysis of characteristic patterns and waveforms it is possible to distinguish wakefulness and five sleep stages. Sleep and the sleep stages modulate autonomous nervous system functions such as body temperature, respiration, blood pressure, and heart rate. These functions consist of a sympathetic tone usually related to activation and to parasympathetic (or vagal) tone usually related to inhibition. Methods of statistical physics are used to analyze heart rate and respiration to detect changes of the autonomous nervous system during sleep. Detrended fluctuation analysis and synchronization analysis and their applications to heart rate and respiration during sleep in healthy subjects and patients with sleep disorders are presented. The observed changes can be used to distinguish sleep stages in healthy subjects as well as to differentiate normal and disturbed sleep on the basis of heart rate and respiration recordings without direct recording of brain waves. Of special interest are the cardiovascular consequences of disturbed sleep because they present a risk factor for cardiovascular disorders such as arterial hypertension, cardiac ischemia, sudden cardiac death, and stroke. New derived variables can help to find indicators for these health risks.

TRPA1 and Sympathetic Activation contribute to increased risk of triggered cardiac arrhythmias in hypertensive rats exposed to diesel exhaust

EPA Science Inventory

Background -Diesel exhaust (DE), which is emitted from on-and off-road sources, is a complex mixture of toxic gaseous and particulate components that results in adverse cardiovascular effects. Arrhythmias, which are often triggered in the hours and days following exposure, are on...

Cardiovascular effects of vasopressin following V(1) receptor blockade compared to effects of nitroglycerin.

PubMed

Cooke, C R; Wall, B M; Huch, K M; Mangold, T

2001-09-01

Studies to more clearly determine the mechanisms associated with arginine vasopressin (AVP)-induced vasodilation were performed in normal subjects and in quadriplegic subjects with impaired efferent sympathetic responses. Studies to compare the effects of AVP with the hemodynamic effects of nitroglycerin, an agent that primarily affects venous capacitance vessels, were also performed in normal subjects. Incremental infusions of AVP following V(1)-receptor blockade resulted in equivalent reductions in systemic vascular resistance (SVRI) in normal and in quadriplegic subjects. However, there were major differences in the effect on mean arterial pressure (MAP), which was reduced in quadriplegic subjects but did not change in normal subjects. This difference in MAP can be attributed to a difference in the magnitude of increase in cardiac output (CI), which was twofold greater in normal than in quadriplegic subjects. These observations are consistent with AVP-induced vasodilation of arterial resistance vessels with reflex sympathetic enhancement of CI and are clearly different from the hemodynamic effects of nitroglycerin, i.e., reductions in MAP, CI, and indexes of cardiac preload, with only minor changes in SVRI.

Pacing-induced palmar sweating evaluated by unique hygrometer: possible implications of sympathetic activation during tachycardia.

PubMed

Maruyama, T; Yanaga, T; Makino, N

2000-03-01

Although reflex sympathetic activation is a major determinant of the haemodynamic tolerability of ventricular tachycardia (VT), the methods for evaluating this aspect during on-going VT remain invasive and complicated. Palmar sweating as an indirect but non-invasive measure of sympathetic activity was estimated by means of a unique hygrometer under right ventricular (RV) rapid pacing (up to 150 beats min-1) replicating VT, and concurrent monitoring of aortic blood pressure in five patients with various kinds of cardiac arrhythmias in our electrophysiological laboratory. The peak palmar sweating rate in arbitrary units was augmented as the RV pacing rate increased and was proportional to the pacing-induced fall in systolic blood pressure (SBP), with a correlation coefficient of more than 0.903 (P<0.006). The slope of linearity between the sweating rate and the fall in SBP varied among individual patients, with greater sweating amplitude in the younger patients even with the same extent of fall in SBP. This preliminary study suggests sympathetic acceleration caused by haemodynamic deterioration under simulated VT, and therefore this protocol may be able to predict the haemodynamic tolerability of sustained monomorphic VT.

Autonomic, functional, skeletal muscle, and cardiac abnormalities are associated with increased ergoreflex sensitivity in mitochondrial disease.

PubMed

Giannoni, Alberto; Aimo, Alberto; Mancuso, Michelangelo; Piepoli, Massimo Francesco; Orsucci, Daniele; Aquaro, Giovanni Donato; Barison, Andrea; De Marchi, Daniele; Taddei, Claudia; Cameli, Matteo; Raglianti, Valentina; Siciliano, Gabriele; Passino, Claudio; Emdin, Michele

2017-12-01

Mitochondrial disease (MD) is a genetic disorder affecting skeletal muscles, with possible myocardial disease. The ergoreflex, sensitive to skeletal muscle work, regulates ventilatory and autonomic responses to exercise. We hypothesized the presence of an increased ergoreflex sensitivity in MD patients, its association with abnormal ventilatory and autonomic responses, and possibly with subclinical cardiac involvement. Twenty-five MD patients (aged 46 ± 3 years, 32% male) with skeletal myopathy but without known cardiac disease, underwent a thorough evaluation including BNPs, galectin-3, soluble suppression of tumorigenesis 2 (sST2), high sensitivity troponin T/I, catecholamines, ECG, 24-h ECG recording, cardiopulmonary exercise testing, echocardiography, cardiac/muscle magnetic resonance (C/MMR), and ergoreflex assessment. Thirteen age- and sex-matched healthy controls were chosen. Among these myopathic patients, subclinical cardiac damage was detected in up to 80%, with 44% showing fibrosis at CMR. Ergoreflex sensitivity was markedly higher in patients than in controls (64% vs. 37%, P < 0.001), and correlated with muscle fat to water ratio and extracellular volume at MMR (both P < 0.05). Among patients, ergoreflex sensitivity was higher in those with cardiac involvement (P = 0.034). Patients showed a lower peak oxygen consumption (VO 2 /kg) than controls (P < 0.001), as well as ventilatory inefficiency (P = 0.024). Ergoreflex sensitivity correlated with reduced workload and peak VO 2 /kg (both P < 0.001), and several indicators of autonomic imbalance (P < 0.05). Plasma norepinephrine was the unique predictor of myocardial fibrosis at univariate analysis (P < 0.05). Skeletal myopathy in MD is characterized by enhanced ergoreflex sensitivity, which is associated with a higher incidence of cardiac involvement, exercise intolerance, and sympathetic activation. © 2017 The Authors. European Journal of Heart Failure © 2017 European Society of Cardiology.

Non-Gaussianity of Low Frequency Heart Rate Variability and Sympathetic Activation: Lack of Increases in Multiple System Atrophy and Parkinson Disease

PubMed Central

Kiyono, Ken; Hayano, Junichiro; Kwak, Shin; Watanabe, Eiichi; Yamamoto, Yoshiharu

2012-01-01

The correlates of indices of long-term ambulatory heart rate variability (HRV) of the autonomic nervous system have not been completely understood. In this study, we evaluated conventional HRV indices, obtained from the daytime (12:00–18:00) Holter recording, and a recently proposed non-Gaussianity index (λ; Kiyono et al., 2008) in 12 patients with multiple system atrophy (MSA) and 10 patients with Parkinson disease (PD), known to have varying degrees of cardiac vagal and sympathetic dysfunction. Compared with the age-matched healthy control group, the MSA patients showed significantly decreased HRV, most probably reflecting impaired vagal heart rate control, but the PD patients did not show such reduced variability. In both MSA and PD patients, the low-to-high frequency (LF/HF) ratio and the short-term fractal exponent α1, suggested to reflect the sympathovagal balance, were significantly decreased, as observed in congestive heart failure (CHF) patients with sympathetic overdrive. In contrast, the analysis of the non-Gaussianity index λ showed that a marked increase in intermittent and non-Gaussian HRV observed in the CHF patients was not observed in the MSA and PD patients with sympathetic dysfunction. These findings provide additional evidence for the relation between the non-Gaussian intermittency of HRV and increased sympathetic activity. PMID:22371705

Mechanisms of cardiac cell damage due to catecholamines: significance of drugs regulating central sympathetic outflow.

PubMed

Rupp, H; Dhalla, K S; Dhalla, N S

1994-01-01

A chronically increased rate of catecholamine release has various deleterious actions. Isoproterenol injections (80 mg/kg body weight) resulted in depressed Ca2+ transport in the sarcolemma (ATP-dependent Ca2+ uptake, Na(+)-dependent Ca2+ uptake) and sarcoplasmic reticulum (Ca2+ uptake) of rat heart. The formation of malondialdehyde owing to lipid peroxidation was increased. Pretreatment with vitamin E (10-25 mg/kg/day) strongly inhibited the membrane damage. The toxic effects of catecholamines arise most probably from their oxidation, and it is therefore important either to reduce the central sympathetic outflow or to prevent the oxidation. An inappropriately high sympathetic outflow is a typical feature of Western affluent societies, and is linked to psychosocial stress and hypercaloric nutrition. However, established pharmacologic interventions to reduce sympathetic outflow have proven not practicable because of marked side effects. Using radiotelemetry for monitoring cardiovascular parameters of spontaneously hypertensive rats treated with clonidine or moxonidine, we showed that clonidine, unlike moxonidine, resulted in rebound hypertension after drug withdrawal. Because the rebound blood pressure and the typical side effects of clonidine associated with low patient compliance are mainly mediated by alpha-adrenoceptors, it can be inferred that the I1-imidazoline agonist moxonidine does not exhibit the side effects commonly seen with clonidine and therefore represents a promising approach for reducing an inappropriately high central sympathetic outflow.

Utility of Autonomic Function Tests to Differentiate Dementia with Lewy Bodies and Parkinson Disease with Dementia from Alzheimer Disease.

PubMed

Toru, Shuta; Kanouchi, Tadashi; Yokota, Takanori; Yagi, Yosuke; Machida, Akira; Kobayashi, Takayoshi

2018-01-01

We studied autonomic disturbance in patients with dementia with Lewy bodies (DLB), Parkinson disease with dementia (PDD), Alzheimer disease (AD), to determine whether autonomic function tests can be used to distinguish these disorders. Autonomic function was tested in 56 patients with DLB, 37 patients with PDD, and 59 patients with AD by using the sympathetic skin response, coefficient of variation in R-R interval, the head-up tilt test, serum norepinephrine concentration, and 123I-meta-iodobenzylguanidine cardiac scintigraphy. Symptoms of autonomic dysfunction, such as constipation, urinary symptoms, and orthostatic hypotension, were also noted. The groups did not differ on baseline characteristics other than those associated with Parkinsonism and dementia. All patients with DLB and PDD had some dysautonomia, whereas rates were much lower for patients with AD (19%). Significantly more DLB and PDD patients than AD patients showed abnormalities on autonomic function tests. Autonomic function tests might be quite useful to distinguish DLB and PDD from AD. © 2017 S. Karger AG, Basel.

Autonomic dysfunction in muscular dystrophy: a theoretical framework for muscle reflex involvement

PubMed Central

Smith, Scott A.; Downey, Ryan M.; Williamson, Jon W.; Mizuno, Masaki

2014-01-01

Muscular dystrophies are a heterogeneous group of genetically inherited disorders whose most prominent clinical feature is progressive degeneration of skeletal muscle. In several forms of the disease, the function of cardiac muscle is likewise affected. The primary defect in this group of diseases is caused by mutations in myocyte proteins important to cellular structure and/or performance. That being stated, a growing body of evidence suggests that the development of autonomic dysfunction may secondarily contribute to the generation of skeletal and cardio-myopathy in muscular dystrophy. Indeed, abnormalities in the regulation of both sympathetic and parasympathetic nerve activity have been reported in a number of muscular dystrophy variants. However, the mechanisms mediating this autonomic dysfunction remain relatively unknown. An autonomic reflex originating in skeletal muscle, the exercise pressor reflex, is known to contribute significantly to the control of sympathetic and parasympathetic activity when stimulated. Given the skeletal myopathy that develops with muscular dystrophy, it is logical to suggest that the function of this reflex might also be abnormal with the pathogenesis of disease. As such, it may contribute to or exacerbate the autonomic dysfunction that manifests. This possibility along with a basic description of exercise pressor reflex function in health and disease are reviewed. A better understanding of the mechanisms that possibly underlie autonomic dysfunction in muscular dystrophy may not only facilitate further research but could also lead to the identification of new therapeutic targets for the treatment of muscular dystrophy. PMID:24600397

Short-term supervised inpatient physiotherapy exercise protocol improves cardiac autonomic function after coronary artery bypass graft surgery--a randomised controlled trial.

PubMed

Mendes, Renata Gonçalves; Simões, Rodrigo Polaquini; De Souza Melo Costa, Fernando; Pantoni, Camila Bianca Falasco; Di Thommazo, Luciana; Luzzi, Sérgio; Catai, Aparecida Maria; Arena, Ross; Borghi-Silva, Audrey

2010-01-01

Coronary artery bypass grafting (CABG) is accompanied by severe impairment of cardiac autonomous regulation (CAR). This study aimed to determine whether a short-term physiotherapy exercise protocol post-CABG, during inpatient cardiac rehabilitation (CR), might improve CAR. Seventy-four patients eligible for CABG were recruited and randomised into physiotherapy exercise group (EG) or physiotherapy usual care group (UCG). EG patients underwent a short-term supervised inpatient physiotherapy exercise protocol consisting of an early mobilisation with progressive exercises plus usual care (respiratory exercises). UCG only received respiratory exercises. Forty-seven patients (24 EG and 23 UGC) completed the study. Outcome measures of CAR included linear and non-linear measures of heart rate variability (HRV) assessed before discharge. By hospital discharge, EG presented significantly higher parasympathetic HRV values [rMSSD, high frequency (HF), SD1)], global power (STD RR, SD2), non-linear HRV indexes [detrended fluctuation analysis (DFA)alpha1, DFAalpha2, approximate entropy (ApEn)] and mean RR compared to UCG (p<0.05). Conversely, higher values of mean HR, low frequency (LF) (sympathetic activity) and the LF/HF (global sympatho-vagal balance) were found in the UCG. A short-term supervised physiotherapy exercise protocol during inpatient CR improves CAR at the time of discharge. Thus, exercise-based inpatient CR might be an effective non-pharmacological tool to improve autonomic cardiac tone in patient's post-CABG.

[Evaluation of crossing calibration of (123)I-MIBG H/M ration, with the IDW scatter correction method, on different gamma camera systems].

PubMed

Kittaka, Daisuke; Takase, Tadashi; Akiyama, Masayuki; Nakazawa, Yasuo; Shinozuka, Akira; Shirai, Muneaki

2011-01-01

(123)I-MIBG Heart-to-Mediastinum activity ratio (H/M) is commonly used as an indicator of relative myocardial (123)I-MIBG uptake. H/M ratios reflect myocardial sympathetic nerve function, therefore it is a useful parameter to assess regional myocardial sympathetic denervation in various cardiac diseases. However, H/M ratio values differ by site, gamma camera system, position and size of region of interest (ROI), and collimator. In addition to these factors, 529 keV scatter component may also affect (123)I-MIBG H/M ratio. In this study, we examined whether the H/M ratio shows correlation between two different gamma camera systems and that sought for H/M ratio calculation formula. Moreover, we assessed the feasibility of (123)I Dual Window (IDW) method, which is a scatter correction method, and compared H/M ratios with and without IDW method. H/M ratio displayed a good correlation between two gamma camera systems. Additionally, we were able to create a new H/M calculation formula. These results indicated that the IDW method is a useful scatter correction method for calculating (123)I-MIBG H/M ratios.

Regulation of muscle sympathetic nerve activity after bed rest deconditioning

NASA Technical Reports Server (NTRS)

Pawelczyk, J. A.; Zuckerman, J. H.; Blomqvist, C. G.; Levine, B. D.

2001-01-01

Cardiovascular deconditioning reduces orthostatic tolerance. To determine whether changes in autonomic function might produce this effect, we developed stimulus-response curves relating limb vascular resistance, muscle sympathetic nerve activity (MSNA), and pulmonary capillary wedge pressure (PCWP) with seven subjects before and after 18 days of -6 degrees head-down bed rest. Both lower body negative pressure (LBNP; -15 and -30 mmHg) and rapid saline infusion (15 and 30 ml/kg body wt) were used to produce a wide variation in PCWP. Orthostatic tolerance was assessed with graded LBNP to presyncope. Bed rest reduced LBNP tolerance from 23.9 +/- 2.1 to 21.2 +/- 1.5 min, respectively (means +/- SE, P = 0.02). The MSNA-PCWP relationship was unchanged after bed rest, though at any stage of the LBNP protocol PCWP was lower, and MSNA was greater. Thus bed rest deconditioning produced hypovolemia, causing a shift in operating point on the stimulus-response curve. The relationship between limb vascular resistance and MSNA was not significantly altered after bed rest. We conclude that bed rest deconditioning does not alter reflex control of MSNA, but may produce orthostatic intolerance through a combination of hypovolemia and cardiac atrophy.

Heart Rate and Heart Rate Variability in Dairy Cows with Different Temperament and Behavioural Reactivity to Humans

PubMed Central

Tőzsér, János; Szenci, Ottó; Póti, Péter; Pajor, Ferenc

2015-01-01

From the 1990s, extensive research was started on the physiological aspects of individual traits in animals. Previous research has established two extreme (proactive and reactive) coping styles in several animal species, but the means of reactivity with the autonomic nervous system (ANS) activity has not yet been investigated in cattle. The aim of this study was the characterization of cardiac autonomic activity under different conditions in cows with different individual characteristics. For this purpose, we investigated heart rate and ANS-related heart rate variability (HRV) parameters of dairy cows (N = 282) on smaller- and larger-scale farms grouped by (1) temperament and (2) behavioural reactivity to humans (BRH). Animals with high BRH scores were defined as impulsive, while animals with low BRH scores were defined as reserved. Cardiac parameters were calculated for undisturbed lying (baseline) and for milking bouts, the latter with the presence of an unfamiliar person (stressful situation). Sympathetic tone was higher, while vagal activity was lower in temperamental cows than in calm animals during rest both on smaller- and larger-scale farms. During milking, HRV parameters were indicative of a higher sympathetic and a lower vagal activity of temperamental cows as compared to calm ones in farms of both sizes. Basal heart rate did not differ between BRH groups either on smaller- or larger-scale farms. Differences between basal ANS activity of impulsive and reserved cows reflected a higher resting vagal and lower sympathetic activity of reserved animals compared to impulsive ones both on smaller- and larger-scale farms. There was no difference either in heart rate or in HRV parameters between groups during milking neither in smaller- nor in larger-scale farms. These two groupings allowed to draw possible parallels between personality and cardiac autonomic activity during both rest and milking in dairy cows. Heart rate and HRV seem to be useful for characterisation of physiological differences related to temperament and BRH. PMID:26291979

Human muscle sympathetic neural and haemodynamic responses to tilt following spaceflight

NASA Technical Reports Server (NTRS)

Levine, Benjamin D.; Pawelczyk, James A.; Ertl, Andrew C.; Cox, James F.; Zuckerman, Julie H.; Diedrich, Andre; Biaggioni, Italo; Ray, Chester A.; Smith, Michael L.; Iwase, Satoshi;

Human muscle sympathetic neural and haemodynamic responses to tilt following spaceflight

PubMed Central

Levine, Benjamin D; Pawelczyk, James A; Ertl, Andrew C; Cox, James F; Zuckerman, Julie H; Diedrich, André; Biaggioni, Italo; Ray, Chester A; Smith, Michael L; Iwase, Satoshi; Saito, Mitsuru; Sugiyama, Yoshiki; Mano, Tadaaki; Zhang, Rong; Iwasaki, Kenichi; Lane, Lynda D; Buckey, Jay C; Cooke, William H; Baisch, Friedhelm J; Robertson, David; Eckberg, Dwain L; Blomqvist, C Gunnar

2002-01-01

Orthostatic intolerance is common when astronauts return to Earth: after brief spaceflight, up to two-thirds are unable to remain standing for 10 min. Previous research suggests that susceptible individuals are unable to increase their systemic vascular resistance and plasma noradrenaline concentrations above pre-flight upright levels. In this study, we tested the hypothesis that adaptation to the microgravity of space impairs sympathetic neural responses to upright posture on Earth. We studied six astronauts ∼72 and 23 days before and on landing day after the 16 day Neurolab space shuttle mission. We measured heart rate, arterial pressure and cardiac output, and calculated stroke volume and total peripheral resistance, during supine rest and 10 min of 60 deg upright tilt. Muscle sympathetic nerve activity was recorded in five subjects, as a direct measure of sympathetic nervous system responses. As in previous studies, mean (± s.e.m.) stroke volume was lower (46 ± 5 vs. 76 ± 3 ml, P = 0.017) and heart rate was higher (93 ± 1 vs. 74 ± 4 beats min−1, P = 0.002) during tilt after spaceflight than before spaceflight. Total peripheral resistance during tilt post flight was higher in some, but not all astronauts (1674 ± 256 vs. 1372 ± 62 dynes s cm−5, P = 0.32). No crew member exhibited orthostatic hypotension or presyncopal symptoms during the 10 min of postflight tilting. Muscle sympathetic nerve activity was higher post flight in all subjects, in supine (27 ± 4 vs. 17 ± 2 bursts min−1, P = 0.04) and tilted (46 ± 4 vs. 38 ± 3 bursts min−1, P = 0.01) positions. A strong (r2 = 0.91–1.00) linear correlation between left ventricular stroke volume and muscle sympathetic nerve activity suggested that sympathetic responses were appropriate for the haemodynamic challenge of upright tilt and were unaffected by spaceflight. We conclude that after 16 days of spaceflight, muscle sympathetic nerve responses to upright tilt are normal. PMID:11773340

The renal nerves in chronic heart failure: efferent and afferent mechanisms

PubMed Central

Schiller, Alicia M.; Pellegrino, Peter R.; Zucker, Irving H.

2015-01-01

The function of the renal nerves has been an area of scientific and medical interest for many years. The recent advent of a minimally invasive catheter-based method of renal denervation has renewed excitement in understanding the afferent and efferent actions of the renal nerves in multiple diseases. While hypertension has been the focus of much this work, less attention has been given to the role of the renal nerves in the development of chronic heart failure (CHF). Recent studies from our laboratory and those of others implicate an essential role for the renal nerves in the development and progression of CHF. Using a rabbit tachycardia model of CHF and surgical unilateral renal denervation, we provide evidence for both renal efferent and afferent mechanisms in the pathogenesis of CHF. Renal denervation prevented the decrease in renal blood flow observed in CHF while also preventing increases in Angiotensin-II receptor protein in the microvasculature of the renal cortex. Renal denervation in CHF also reduced physiological markers of autonomic dysfunction including an improvement in arterial baroreflex function, heart rate variability, and decreased resting cardiac sympathetic tone. Taken together, the renal sympathetic nerves are necessary in the pathogenesis of CHF via both efferent and afferent mechanisms. Additional investigation is warranted to fully understand the role of these nerves and their role as a therapeutic target in CHF. PMID:26300788

Possible mechanism by which renal sympathetic denervation improves left ventricular remodelling after myocardial infarction.

PubMed

Zheng, Xiao-Xin; Li, Xiao-Yan; Lyu, Yong-Nan; He, Yi-Yu; Wan, Wei-Guo; Zhu, Hong-Ling; Jiang, Xue-Jun

2016-02-01

What is the central question of this study? The enzyme system that is responsible for extracellular matrix (ECM) turnover is the matrix metalloproteinases (MMPs), which can be blocked by the tissue inhibitors of MMPs (TIMPs). Whether renal sympathetic denervation (RSD) is able to ameliorate post-myocardial infarction left ventricular remodelling through attenuation of ECM via regulation of MMP activity and/or the MMP-TIMP complex remains unknown. What is the main finding and its importance? Renal sympathetic denervation has therapeutic effects on post-myocardial infarction left ventricular remodelling, probably by attenuating the ECM through regulation of the MMP9-TIMP1 complex in the transforming growth factor-β1 (a profibrotic cytokine that accelerates ECM remodelling after ischaemia) signalling pathway. Whether renal sympathetic denervation (RSD) is able to ameliorate post-myocardial infarction (post-MI) left ventricular (LV) remodelling by attenuation of the extracellular matrix via regulation of matrix metalloproteinase (MMP) activity and/or the MMP-tissue inhibitor of matrix metalloproteinase (TIMP) complex remains unknown. Sixty-five Sprague-Dawley rats were randomly divided into the following four groups: normal (N, n = 15), RSD (RSD, n = 15), myocardial infarction (MI, n = 15) and RSD 3 days after MI (MI3d+RSD, n = 20). The bilateral renal nerves were surgically denervated 3 days after MI had been induced by coronary artery ligation. Left ventricular function was assessed using echocardiography and a Millar catheter at 6 weeks post-MI. Plasma noradrenaline, angiotensin II and aldosterone, collagen volume fraction, transforming growth factor-β1 (TGF-β1), MMP2, MMP9 and TIMP1 in heart tissue were measured 6 weeks after MI. In rats with MI3d+RSD compared with MI rats, RSD improved systolic and diastolic function, resulting in an improvement in ejection fraction (P < 0.05), fractional shortening (P < 0.05) and LV internal dimension in systole (P < 0.05) and diastole (P < 0.05). Additionally, RSD treatment decreased left ventricular end-diastolic pressure (P < 0.05) and increased LV systolic pressure (P < 0.05) and maximal and minimal rate of LV pressure (both P < 0.05). Meanwhile, RSD reduced collagen content (P < 0.01). TIMP1 was upregulated (P < 0.05), whereas MMP2, MMP9 and TGF-β1 were downregulated in the LV of RSD-treated animals (P < 0.05). Renal sympathetic denervation has therapeutic effects on post-MI LV remodelling, probably owing to effects on the extracellular matrix by regulation of the MMP9-TIMP1 balance in the TGF-β1 signalling pathway. Renal sympathetic denervation may be considered as a non-pharmacological approach for the improvement of post-MI cardiac dysfunction. © 2015 The Authors. Experimental Physiology © 2015 The Physiological Society.

Nervous kidney. Interaction between renal sympathetic nerves and the renin-angiotensin system in the control of renal function.

PubMed

DiBona, G F

2000-12-01

Increases in renal sympathetic nerve activity regulate the functions of the nephron, the vasculature, and the renin-containing juxtaglomerular granular cells. Because increased activity of the renin-angiotensin system can also influence nephron and vascular function, it is important to understand the interactions between the renal sympathetic nerves and the renin-angiotensin system in the control of renal function. These interactions can be intrarenal, for example, the direct (by specific innervation) and indirect (by angiotensin II) contributions of increased renal sympathetic nerve activity to the regulation of renal function. The effects of increased renal sympathetic nerve activity on renal function are attenuated when the activity of the renin-angiotensin system is suppressed or antagonized with ACE inhibitors or angiotensin II-type AT(1)-receptor antagonists. The effects of intrarenal administration of angiotensin II are attenuated after renal denervation. These interactions can also be extrarenal, for example, in the central nervous system, wherein renal sympathetic nerve activity and its arterial baroreflex control are modulated by changes in activity of the renin-angiotensin system. In addition to the circumventricular organs, whose permeable blood-brain barrier permits interactions with circulating angiotensin II, there are interactions at sites behind the blood-brain barrier that depend on the influence of local angiotensin II. The responses to central administration of angiotensin II-type AT(1)-receptor antagonists into the ventricular system or microinjected into the rostral ventrolateral medulla are modulated by changes in activity of the renin-angiotensin system produced by physiological changes in dietary sodium intake. Similar modulation is observed in pathophysiological models wherein activity of both the renin-angiotensin and sympathetic nervous systems is increased (eg, congestive heart failure). Thus, both renal and extrarenal sites of interaction between the renin-angiotensin system and renal sympathetic nerve activity are involved in influencing the neural control of renal function.

Chemistry and biology of radiotracers that target changes in sympathetic and parasympathetic nervous systems in heart disease.

PubMed

Eckelman, William C; Dilsizian, Vasken

2015-06-01

Following the discovery of the sympathetic and parasympathetic nervous system, numerous adrenoceptor drugs were radiolabeled and potent radioligands were prepared in order to image the β-adrenergic and the muscarinic systems. But the greatest effort has been in preparing noradrenaline analogs, such as norepinephrine, (11)C-metahydroxyephedrine, and (123)I-metaiodobenzylguanidine that measure cardiac sympathetic nerve varicosities. Given the technical and clinical challenges in designing and validating targeted adrenoceptor-binding radiotracers, namely the heavily weighted flow dependence and relatively low target-to-background ratio, both requiring complicated mathematic analysis, and the inability of targeted adrenoceptor radioligands to have an impact on clinical care of heart disease, the emphasis has been on radioligands monitoring the norepinephrine pathway. The chemistry and biology of such radiotracers, and the clinical and prognostic impact of these innervation imaging studies in patients with heart disease, are examined. © 2015 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Baroreflex dysfunction induced by microgravity: potential relevance to postflight orthostatic intolerance

NASA Technical Reports Server (NTRS)

Ertl, A. C.; Diedrich, A.; Biaggioni, I.; Robertson, D. (Principal Investigator)

2000-01-01

Microgravity imposes adaptive changes in the human body. This review focuses on the changes in baroreflex function produced by actual spaceflight, or by experimental models that simulate microgravity, e.g., bed rest. We will analyze separately studies involving baroreflexes arising from carotid sinus and aortic arch afferents ("high-pressure baroreceptors"), and cardiopulmonary afferents ("low-pressure receptors"). Studies from unrelated laboratories using different techniques have concluded that actual or simulated exposure to microgravity reduces baroreflex function arising from carotid sinus afferents ("carotic-cardiac baroreflex"). The techniques used to study the carotid-cardiac baroreflex, using neck suction and compression to simulate changes in blood pressure, have been extensively validated. In contrast, it is more difficult to selectively study aortic arch or cardiopulmonary baroreceptors. Nonetheless, studies that have examined these baroreceptors suggest that microgravity produces the opposite effect, ie, an increase in the gain of aortic arch and cardiopulmonary baroreflexes. Furthermore, most studies have focus on instantaneous changes in heart rate, which almost exclusively examines the vagal limb of the baroreflex. In comparison, there is limited information about the effect of microgravity on sympathetic function. A substantial proportion of subjects exposed to microgravity develop transient orthostatic intolerance. It has been proposed that alterations in baroreflex function play a role in the orthostatic intolerance induced by microgravity. The evidence in favor and against this hypothesis is reviewed.

Recurrent postoperative CRPS I in patients with abnormal preoperative sympathetic function.

PubMed

Ackerman, William E; Ahmad, Mahmood

2008-02-01

A complex regional pain syndrome of an extremity that has previously resolved can recur after repeat surgery at the same anatomic site. Complex regional pain syndrome is described as a disease of the autonomic nervous system. The purpose of this study was to evaluate preoperative and postoperative sympathetic function and the recurrence of complex regional pain syndrome type I (CRPS I) in patients after repeat carpal tunnel surgery. Thirty-four patients who developed CRPS I after initial carpal tunnel releases and required repeat open carpal tunnel surgeries were studied. Laser Doppler imaging (LDI) was used to assess preoperative sympathetic function 5-7 days prior to surgery and to assess postoperative sympathetic function 19-22 days after surgery or 20-22 days after resolution of the CRPS I. Sympathetic nervous system function was prospectively examined by testing reflex-evoked vasoconstrictor responses to sympathetic stimuli recorded with LDI of both hands. Patients were assigned to 1 of 2 groups based on LDI responses to sympathetic provocation. Group I (11 of 34) patients had abnormal preoperative LDI studies in the hands that had prior surgeries, whereas group II (23 of 34) patients had normal LDI studies. Each patient in this study had open repeat carpal tunnel surgery. In group I, 8 of 11 patients had recurrent CRPS I, whereas in group II, 3 of 23 patients had recurrent CRPS I. All of the recurrent CRPS I patients were successfully treated with sympathetic blockade, occupational therapy, and pharmacologic modalities. Repeat LDI after recurrent CRPS I resolution was abnormal in 8 of 8 group I patients and in 1 of 3 group II patients. CRPS I can recur after repeat hand surgery. Our study results may, however, identify those individuals who may readily benefit from perioperative therapies. Prognostic I.

Central and peripheral nervous systems: master controllers in cancer metastasis.

PubMed

Shi, Ming; Liu, Dan; Yang, Zhengyan; Guo, Ning

2013-12-01

Central and sympathetic nervous systems govern functional activities of many organs. Solid tumors like organs are also innervated by sympathetic nerve fibers. Neurotransmitters released from sympathetic nerve fibers can modulate biological behaviors of tumor cells. Multiple physiologic processes of tumor development may be dominated by central and sympathetic nervous systems as well. Recent studies suggest that dysfunction of central and sympathetic nervous systems and disorder of the hormone network induced by psychological stress may influence malignant progression of cancer by inhibiting the functions of immune system, regulating metabolic reprogramming of tumor cells, and inducing interactions between tumor and stromal cells. Over-release of inflammatory cytokines by tumors may aggravate emotional disorder, triggering the vicious cycles in tumor microenvironment and host macroenvironment. It is reasonable to hypothesize that cancer progression may be controlled by central and sympathetic nervous systems. In this review, we will focus on the recent information about the impacts of central and sympathetic nervous systems on tumor invasion and metastasis.

Dose-related effects of red wine and alcohol on hemodynamics, sympathetic nerve activity, and arterial diameter.

PubMed

Spaak, Jonas; Merlocco, Anthony C; Soleas, George J; Tomlinson, George; Morris, Beverley L; Picton, Peter; Notarius, Catherine F; Chan, Christopher T; Floras, John S

2008-02-01

The cardiovascular benefits of light to moderate red wine consumption often have been attributed to its polyphenol constituents. However, the acute dose-related hemodynamic, vasodilator, and sympathetic neural effects of ethanol and red wine have not been characterized and compared in the same individual. We sought to test the hypotheses that responses to one and two alcoholic drinks differ and that red wine with high polyphenol content elicits a greater effect than ethanol alone. Thirteen volunteers (24-47 yr; 7 men, 6 women) drank wine, ethanol, and water in a randomized, single-blind trial on three occasions 2 wk apart. One drink of wine and ethanol increased blood alcohol to 38 +/- 2 and 39 +/- 2 mg/dl, respectively, and two drinks to 72 +/- 4 and 83 +/- 3 mg/dl, respectively. Wine quadrupled plasma resveratrol (P < 0.001) and increased catechin (P < 0.03). No intervention affected blood pressure. One drink had no heart rate effect, but two drinks of wine increased heart rate by 5.7 +/- 1.6 beats/min; P < 0.001). Cardiac output fell 0.8 +/- 0.3 l/min after one drink of ethanol and wine (both P < 0.02) but increased after two drinks of ethanol (+0.8 +/- 0.3 l/min) and wine (+1.2 +/- 0.3 l/min) (P < 0.01). One alcoholic drink did not alter muscle sympathetic nerve activity (MSNA), while two drinks increased MSNA by 9-10 bursts/min (P < 0.001). Brachial artery diameter increased after both one and two alcoholic drinks (P < 0.001). No beverage augmented, and the second wine dose attenuated (P = 0.02), flow-mediated vasodilation. One drink of ethanol dilates the brachial artery without activating sympathetic outflow, whereas two drinks increase MSNA, heart rate, and cardiac output. These acute effects, which exhibit a narrow dose response, are not modified by red wine polyphenols.

Hemodynamic actions and mechanisms of systemically administered α-MSH analogs in mice.

PubMed

Rinne, Petteri; Tikka, Sanna; Mäkelä, Satu; Streng, Tomi; Savontaus, Eriika

2012-11-01

α-Melanocyte-stimulating hormone (α-MSH) regulates important physiological functions including energy homeostasis and inflammation. Potent analogs of α-MSH, [Nle(4), D-Phe(7)]-α-MSH (NDP-α-MSH) and melanotan-II (MT-II), are widely used in pharmacological studies, but the hemodynamic effects associated with their systemic administration have not been thoroughly examined. Therefore, we investigated the hemodynamic actions of these compounds in anesthetized and conscious C57Bl/6N mice using peripheral routes of administration. NDP-α-MSH and MT-II induced mild changes in blood pressure and heart rate in anesthetized mice compared to the effects observed in conscious mice, suggesting that anesthesia distorts the hemodynamic actions of α-MSH analogs. In conscious mice, NDP-α-MSH and MT-II increased blood pressure and heart rate in a dose-dependent manner, but the tachycardic effect was more prominent than the pressor effect. Pretreatment with the melanocortin (MC) 3/4 receptor antagonist SHU9119 abolished these hemodynamic effects. Furthermore, the blockade of β(1)-adrenoceptors with metoprolol prevented the pressor effect and partly the tachycardic action of α-MSH analogs, while the ganglionic blocker hexamethonium abrogated completely the difference in heart rate between vehicle and α-MSH treatments. These findings suggest that the pressor effect is primarily caused by augmentation of cardiac sympathetic activity, but the tachycardic effect seems to involve withdrawal of vagal tone in addition to sympathetic activation. In conclusion, the present results indicate that systemic administration of α-MSH analogs elevates blood pressure and heart rate via activation of MC(3/4) receptor pathways. These effects and the consequent increase in cardiac workload should be taken into account when using α-MSH analogs via peripheral routes of administration. Copyright © 2012 Elsevier Inc. All rights reserved.

Modulation of vascular function by diet and exercise.

PubMed

Jennings, G L; Chin-Dusting, J P; Kingwell, B A; Dart, A M; Cameron, J; Esler, M; Lewis, T V

1997-01-01

Clinical research is conducted in free living individuals who are always subject to the influences on vascular function and the major cardiovascular regulators of their lifestyle. The purpose of this paper is to review some lifestyle influences on cardiovascular function, particularly the sympathetic nervous system and endothelially mediated vasodilatation. There are highly differentiated sympathetic responses to feeding, and to acute exercise. Over a longer period obesity has a typical pattern of sympathetic activity. Reduced dietary salt intake elicits profound localised increases in sympathetic activity to the kidney. Marine oil supplementation attenuates the sympathetic responses to psychological stress and improves endothelially mediated vasodilatation in hypercholesterolaemics. Exercise training reduced total noradrenaline spillover, the major beds affected being the renal and skeletal muscle. These examples illustrate the dynamic nature of vascular dilatation and that, like the sympathetic nervous system, it is modulated by short, medium and long term influences. In both cases there is regulation both at a local and systemic level. Habitual, and recent, lifestyle can exert important cardiovascular effects which must be taken into account in clinical and epidemiological research.

Pharmacological management of chronic heart failure in adults: a review of the literature.

PubMed

Auty, Richard

2004-03-01

Heart failure is a common, life threatening condition encountered in patients of all ages and in all clinical settings. It may be due to any of a wide variety of causes - in Malawi, cardiomyopathies, hypertension and rheumatic heart disease are probably the commonest causes of heart failure. In more affluent societies, ischaemic heart disease is an important factor. Chronic heart failure (CHF) causes significant morbidity: it reduces exercise capacity, interferes with sleep and produces unsightly and uncomfortable oedema. The syndrome also carries substantial mortatity, worse than that of many malignant tumours: 20 -30% of patients with mild or moderately severe heart failure will die every year if left untreated. The life expectancy of a patient with untreated severe heart failure is only about 6 months. Table 1 explains the symptomatic classification of the severity of heart failure. Objective measurements of cardiac function, such as Left Ventricular Ejection Fraction (LYEF) or chamber filling pressures, correlate poorly with symptoms and New York Heart Association (NYHA) classification. Many of the problems experienced by a patient with heart failure are due to a 'vicious circle' of events in which pathophysiological responses to the falling cardiac output cause further deterioration in cardiac function over time. These responses include ventricular remodeling, neurohumoural activation (increased sympathetic activity; increased atrial natriuretic peptide; increased angiotensin II), increased activity of the renin-angiotensin-aldosterone system (RAAS) causing fluid retention, vasoconstriction and sodium retention. [Table: see text].

[Autonomic contribution to the blood pressure and heart rate variability changes in early experimental hyperthyroidism].

PubMed

Safa-Tisseront, V; Ponchon, P; Blanc, J; Elghozi, J L

1998-08-01

A great deal of uncertainty persists regarding the exact nature of the interaction between autonomic nervous activity and thyroid hormones in the control of heart rate (HR) and blood pressure (BP). Thyrotoxicosis was produced by a daily intraperitoneal (i.p.) injection of L-thyroxine (0.5 mg/kg body wt in 1 ml of 5 mM NaOH for 5 days). Control rats received i.p. daily injections of the thyroxine solvant. Autonomic blockers were administered intravenously: atropine (0.5 mg/kg), atenolol (1 mg/kg), atenolol + atropine or prazosin (1 mg/kg). Eight animals were studied in each group. Thyroxine treatment was sufficient to induce a significant degree of tachycardia (423 +/- 6 vs 353 +/- 4 bpm; p < 0.001, unpaired Student's tests), systolic BP elevation (142 +/- 3 vs 127 +/- 2 mmHg; p < 0.001), pulse pressure increase (51 +/- 2 vs 41 +/- 2 mmHg, p < 0.01), cardiac hypertrophy (1.165 +/- 0.017 vs 1.006 +/- 0.012 g, p < 0.001), weight loss (-21 +/- 2 g; p < 0.001) and hyperthermia (37.8 +/- 0.1 vs 37.0 +/- 0.1 degrees C, p < 0.001). The intrinsic HR observed after double blockade (atenolol + atropine) was markedly increased after treatment with thyroxine (497 +/- 16 vs 373 +/- 10 bpm, p < 0.05). Vagal tone (difference between HR obtained after atenolol and intrinsic HR) was positively linearly related to intrinsic HR (r = 0.84; p < 0.01). Atenolol neither modified HR nor BP variability in rats with hyperthyrodism. The thyrotoxicosis was associated with a reduction of the 0.4 Hz component of BP variability (analyses on 102.4 sec segments, modulus 1.10 +/- 0.07 vs 1.41 +/- 0.06 mmHg; p < 0.01). Prazosin was without effect on this 0.4 Hz component in these animals. These data show a functional diminution of the vascular and cardiac sympathetic tone in experimental hyperthyroidism. Increased intrinsic HR resulting from the direct effect of thyroid hormone on the sinoatrial node is the main determinant of a tachycardia leading to a subsequent rise in cardiac output. The resulting BP elevation could reflexly induce a vagal activation and a sympathetic (vascular and cardiac) inhibition.

Intersections between cardiac physiology, emotion regulation and interpersonal warmth in preschoolers: Implications for drug abuse prevention from translational neuroscience

PubMed Central

Clark, Caron A. C.; Skowron, Elizabeth A.; Giuliano, Ryan J.; Fisher, Philip A.

2016-01-01

Background Early childhood is characterized by dramatic gains in emotion regulation skills that support social adjustment and mental health. Understanding the physiological substrates of healthy emotion regulation may offer new directions for altering trajectories towards initiation and escalation of substance abuse. Here, we describe the intersections between parasympathetic and sympathetic tone, emotion regulation and prosocial behavior in a high-risk sample of preschoolers. Method Fifty-two 3 – 6 year old children completed an assessment of attention regulation in response to affective stimuli. Cardiac respiratory sinus arrhythmia, an index of parasympathetic tone, and pre-ejection period, a marker of sympathetic activation, were recorded at rest and while children engaged in social interactions with their mothers and an unfamiliar research assistant. Mothers reported on children’s emotional reactivity and prosocial behavior. Results Controlling for age and psychosocial risk, higher parasympathetic tone predicted better attention regulation in response to angry emotion and higher levels of prosocial behavior, whereas a reciprocal pattern of higher parasympathetic tone and lower sympathetic arousal predicted better attention in response to positive emotion and lower emotional reactivity. Children exposed to fewer risk factors and higher levels of maternal warmth were more able to sustain a high level of parasympathetic tone during interaction episodes. Conclusions Findings suggest that autonomic measures represent biomarkers for socio-emotional competence in young children. They also point to the importance of early experiences in the establishment of physiological regulation and the promise of family-based intervention to promote healthy emotion regulation and prevent substance dependence in high-risk populations. PMID:27306733

A general enhancement of autonomic and cortisol responses during social evaluative threat

PubMed Central

Bosch, Jos A.; de Geus, Eco J.C.; Carroll, Douglas; Goedhart, Annebet D.; Anane, Leila A.; van Zanten, Jet J Veldhuizen; Helmerhorst, Eva J.; Edwards, Kate M.

2013-01-01

Objective The idea that distinct psychosocial factors may underlie specific patterns of neuroendocrine stress responses has been a topic of recurrent debate. We examined a recent contribution to this debate, the Social Self Preservation Theory, which predicts that stressors involving social evaluative threat (SET) characteristically activate the hypothalamic-pituitary-adrenal (HPA) axis. Methods Sixty-one healthy university students (31 females) performed a challenging speech task in one of three conditions that aimed to impose increasing levels of SET: performing the task alone (no social evaluation), with 1 evaluating observer, or with 4 evaluating observers. Indices of sympathetic (pre-ejection period) and parasympathetic (heart rate variability) cardiac drive were obtained by impedance- and electrocardiography. Salivary cortisol was used to index HPA activity. Questionnaires assessed affective responses. Results Affective responses (shame/embarrassment, anxiety, negative affect, and self-esteem), cortisol, heart rate, sympathetic, and parasympathetic activation all differentiated evaluative from non-evaluative task conditions (p<.001). The largest effect-sizes were observed for cardiac autonomic responses. Physiological reactivity increased in parallel with increasing audience size (p<.001). A rise in cortisol was predicted by sympathetic activation during the task (p<.001), but not by affective responses. Conclusion It would appear that SET determines the magnitude, rather than the pattern, of physiological activation. This potential to broadly perturb multiple physiological systems may help explain why social stress has been associated with a range of health outcomes. We propose a threshold-activation model as a physiological explanation for why engaging stressors, such as those involving social evaluation or uncontrollability, may appear to selectively induce cortisol release. PMID:19779143

Left cardiac sympathetic denervation: case series and technical report.

PubMed

McNamara, C; Cullen, P; Rackauskas, M; Kelly, R; O'Sullivan, K E; Galvin, J; Eaton, D

2017-08-01

Left cardiac sympathetic denervation (LCSD) is a surgical procedure that has been shown to have an antiarrhythmic and antifibrillatory effect. Evidence indicating its antiarrhythmic effect has been available for over 100 years. It involves the removal of the lower half of the stellate ganglion and T2-T4 of the sympathetic ganglia and is carried out as either a unilateral or bilateral procedure. With advancements in thoracic surgery, it can be safely performed via a minimally invasive Video-Assisted Thoracoscopic Surgery (VATS) approach resulting in significantly less morbidity and a shortened inpatient stay. LCSD provides a valuable treatment option for patients with life-threatening channelopathies and cardiomyopathies. This case series reports the preliminary paediatric and adult experience in the Republic of Ireland with LCSD and describes five cases recently treated in addition to an outline of the operative procedure employed. Of the five cases included, two were paediatric cases and three were adult cases. One of the paediatric patients had a diagnosis of the rare catecholaminergic polymorphic ventricular tachycardia (CPVT) and the other a diagnosis of long-QT syndrome. Both paediatric patients experienced excellent outcomes. Of the three adult patients, two benefitted greatly and remain well at follow-up (one inappropriate sinus tachycardia and one CPVT). One patient with idiopathic ventricular fibrillation unfortunately passed away from intractable VF despite all attempts at resuscitation. In this case series, we highlight that LCSD provides a critical adjunct to existing medical therapies and should be considered for all patients with life-threatening refractory arrhythmias especially those patients on maximal medical therapy.

Empagliflozin lessened cardiac injury and reduced visceral adipocyte hypertrophy in prediabetic rats with metabolic syndrome.

PubMed

Kusaka, Hiroaki; Koibuchi, Nobutaka; Hasegawa, Yu; Ogawa, Hisao; Kim-Mitsuyama, Shokei

2016-11-11

The potential benefit of SGLT2 inhibitors in metabolic syndrome is with prediabetic stage unclear. This work was undertaken to investigate the non-glycemic effect of empagliflozin on metabolic syndrome rats with prediabetes. SHR/NDmcr-cp(+/+) rats (SHRcp), a model of metabolic syndrome with prediabetes, were given empagliflozin for 10 weeks to examine the effects on urinary sodium and water balance, visceral and subcutaneous adipocyte, and cardiac injury. Further, the effect of empagliflozin on blood pressure and autonomic nervous system was continuously investigated by using radiotelemetry system. Empagliflozin significantly reduced urinary sodium and water balance of SHRcp only within 1 week of the treatment, but later than 1 week did not alter them throughout the treatment. Empagliflozin significantly reduced body weight of SHRcp, which was mainly attributed to the significant reduction of subcutaneous fat mass. Empagliflozin significantly reduced the size of visceral adipocytes and increased the number of smaller size of adipocytes, which was associated with the attenuation of oxidative stress. Empagliflozin ameliorated cardiac hypertrophy and fibrosis of SHRcp, in association with the attenuation of cardiac oxidative stress and inflammation. However, empagliflozin did not significantly change blood pressure, heart rate, sympathetic activity, or baroreceptor function, as evidenced by radiotelemetry analysis. Our present work provided the evidence that SGLT2 inhibition reduced visceral adipocytes hypertrophy and ameliorated cardiac injury in prediabetic metabolic syndrome rat, independently of diuretic effect or blood pressure lowering effect. Thus, SGLT2 inhibition seems to be a promising therapeutic strategy for prediabetic metabolic syndrome.

A new look at cardiac defense: attention or emotion?

PubMed

Vila, Jaime; Fernández, María Carmen; Pegalajar, Joaquín; Nieves Vera, María; Robles, Humbelina; Pérez, Nieves; Sánchez, María B; Ramírez, Isabel; Ruiz-Padial, Elisabeth

2003-05-01

The study of cardiac defense has a long tradition in psychological research both within the cognitive approach--linked to Pavlov, Sokolov, and Graham's work on sensory reflexes--and within the motivational one--linked to the work of Cannon and subsequent researchers on the concepts of activation and stress. These two approaches have been difficult to reconcile in the past. We summarize a series of studies on cardiac defense from a different perspective, which allows integration of the traditional approaches. This new perspective emphasizes a sequential process interpretation of the cardiac defense response. Results of descriptive and parametric studies, as well as those of studies examining the physiological and psychological mechanisms underlying the response, show a complex response pattern with both accelerative and decelerative components, with both sympathetic and parasympathetic influences, and with both attentional and emotional significance. The implications of this new look at cardiac defense are discussed in relation to defensive reactions in natural settings, the brain mechanisms controlling such reactions, and their effects on health and illness.

Bilateral thoracoscopic splanchnicectomy for pain in patients with chronic pancreatitis impairs adrenomedullary but not noradrenergic sympathetic function.

PubMed

Buscher, H C J L; Lenders, J W M; Wilder-Smith, O H G; Sweep, C G J; van Goor, H

2012-08-01

Bilateral thoracoscopic splanchnicectomy (BTS) is a well-known technique to alleviate intractable pain in patients with chronic pancreatitis. BTS not only disrupts afferent fibers from the pancreas that mediate pain but also postganglionic sympathetic fibers, which originate in segments T5-T12 and which innervate the vasculature of the liver, pancreas, and the adrenal gland. The purpose of this study was to assess whether and how BTS affects sympathetic noradrenergic and adrenomedullary function in patients with chronic pancreatitis. Sixteen patients with chronic pancreatitis for at least 1 year underwent autonomic function testing before and 6 weeks after BTS for intractable pain. Testing was performed during supine rest and during sympathetic stimulation when standing. Supine and standing systolic and diastolic blood pressure were significantly lower post-BTS compared with pre-BTS (P = 0.001). One patient showed orthostatic hypotension after BTS. Baseline plasma norepinephrine levels and plasma norepinephrine responses to sympathetic activation during standing were not reduced by BTS. In contrast, supine plasma epinephrine levels and responses during standing were significantly reduced (P < 0.001). Parasympathetic activity was unaffected by BTS as shown by unaltered Valsalva ratio, I-E difference, and ΔHRmax. BTS for pain relief in patients with chronic pancreatitis reduced adrenomedullary function, due to disruption of the efferent sympathetic fibers to the adrenal gland. BTS did not affect noradrenergic sympathetic activity, although blood pressure was lower after the sympathectomy.

Neural control of blood pressure in women: differences according to age

PubMed Central

Peinado, Ana B.; Harvey, Ronee E.; Hart, Emma C.; Charkoudian, Nisha; Curry, Timothy B.; Nicholson, Wayne T.; Wallin, B. Gunnar; Joyner, Michael J.; Barnes, Jill N.

2017-01-01

Purpose The blood pressure “error signal” represents the difference between an individual’s mean diastolic blood pressure and the diastolic blood pressure at which 50% of cardiac cycles are associated with a muscle sympathetic nerve activity burst (the “T50”). In this study we evaluated whether T50 and the error signal related to the extent of change in blood pressure during autonomic blockade in young and older women, to study potential differences in sympathetic neural mechanisms regulating blood pressure before and after menopause. Methods We measured muscle sympathetic nerve activity and blood pressure in 12 premenopausal (25±1 years) and 12 postmenopausal women (61±2 years) before and during complete autonomic blockade with trimethaphan camsylate. Results At baseline, young women had a negative error signal (−8±1 versus 2±1 mmHg, p<0.001; respectively) and lower muscle sympathetic nerve activity (15±1 versus 33±3 bursts/min, p<0.001; respectively) than older women. The change in diastolic blood pressure after autonomic blockade was associated with baseline T50 in older women (r=−0.725, p=0.008) but not in young women (r=−0.337, p=0.29). Women with the most negative error signal had the lowest muscle sympathetic nerve activity in both groups (young: r=0.886, p<0.001; older: r=0.870, p<0.001). Conclusions Our results suggest that there are differences in baroreflex control of muscle sympathetic nerve activity between young and older women, using the T50 and error signal analysis. This approach provides further information on autonomic control of blood pressure in women. PMID:28205011

Effect of low-dose scopolamine on autonomic control of the heart

NASA Technical Reports Server (NTRS)

Raeder, E. A.; Stys, A.; Cohen, R. J.

1997-01-01

Background: In low doses, scopolamine paradoxically enhances parasympathetic outflow to the heart. The mechanisms which mediate this action are not fully understood. Moreover, there are conflicting data regarding the potential role of sympathetic activity. This study in 17 healthy individuals was designed to characterize the influence of low dose transdermal scopolamine on the gain of the baroreflex and respiratory heart rate reflex and to determine the role of sympathetic activity. Methods: The effect of scopolamine was analyzed in the time and frequency domain by computing heart rate variability indices. The gains of the respiratory heart rate reflex and the baroreflex were estimated simultaneously by means of a cardiovascular system identification approach using an optimized autoregressive moving average algorithm. Measurements were repeated in the upright posture to assess the influence of enhanced sympathetic activity. In six subjects ambulatory ECGs were recorded to determine whether there are diurnal variations of the effect of scopolamine. Results: Scopolamine enhances vagal modulation of heart rate through both the respiratory-heart rate reflex and the baroreflex, as the gains of both were augmented by the drug in the supine and in the upright postures. Conclusions: Scopolamine increases parasympathetic cardiac control by augmenting the gain of the respiratory-heart rate and baroreflex. This action is not attenuated in the upright posture when sympathetic tone is increased.

The role of sympathetic nervous system in the progression of chronic kidney disease in the era of catheter based sympathetic renal denervation.

PubMed

Petras, Dimitrios; Koutroutsos, Konstantinos; Kordalis, Athanasios; Tsioufis, Costas; Stefanadis, Christodoulos

2013-08-01

The kidney has been shown to be critically involved as both trigger and target of sympathetic nervous system overactivity in both experimental and clinical studies. Renal injury and ischemia, activation of renin angiotensin system and dysfunction of nitric oxide system have been implicated in adrenergic activation from kidney. Conversely, several lines of evidence suggest that sympathetic overactivity, through functional and morphological alterations in renal physiology and structure, may contribute to kidney injury and chronic kidney disease progression. Pharmacologic modulation of sympathetic nervous system activity has been found to have a blood pressure independent renoprotective effect. The inadequate normalization of sympathoexcitation by pharmacologic treatment asks for novel treatment options. Catheter based renal denervation targets selectively both efferent and afferent renal nerves and functionally denervates the kidney providing blood pressure reduction in clinical trials and renoprotection in experimental models by ameliorating the effects of excessive renal sympathetic drive. This review will focus on the role of sympathetic overactivity in the pathogenesis of kidney injury and CKD progression and will speculate on the effect of renal denervation to these conditions.

Influence of Renal Sympathetic Denervation on Cardiac Extracellular Matrix Turnover and Cardiac Fibrosis.

PubMed

Dörr, Oliver; Liebetrau, Christoph; Möllmann, Helge; Gaede, Luise; Troidl, Christian; Morczeck, Kareen; Wiebe, Jens; Hoffmann, Jedrzej; Voss, Sandra; Bauer, Timm; Hamm, Christian; Nef, Holger

2015-10-01

Renal sympathetic denervation (RSD) represents an effective treatment option for patients with resistant arterial hypertension (HT). Extracellular matrix (ECM) turnover and deposition are essential processes in HT-related cardiovascular remodeling, fibrosis, and cardiac hypertrophy and contribute to hypertensive heart disease. The primary aim of the present study was to examine the effect of RSD on increased collagen turnover as reflected by serum levels of amino-terminal pro-peptides (PINP, PIIINP) and a carboxyl-terminal pro-peptide (PICP), specific biomarkers for cardiac ECM turnover and cardiovascular fibrosis. A total of 100 consecutive patients (mean age: 65.9±10.1 years) undergoing RSD were included in this study. A therapeutic response was defined as an office systolic blood pressure (SBP) reduction of >10mm Hg 6 months after RSD. Venous serum samples for measurement of PICP, PINP, and PIIINP were collected prior to and 6 months after RSD. A significant reduction in the office SBP of 24.3 mm Hg (SBP baseline: 166.9±14.3 mm Hg (P < 0.001) was documented 6 months after RSD. At this time point, the serum levels of PICP, PINP, and PIIINP (P < 0.01) were significantly decreased compared to baseline values in patients with an increased collagen turnover, showing significant differences comparing BP responders and nonresponders. In addition to the effective blood pressure reduction in response to RSD, this study demonstrates a positive effect of RSD on biomarkers reflecting cardiovascular ECM turnover and deposition. These results suggest a beneficial effect of RSD on cardiovascular fibrosis, hypertensive heart disease, and end-organ damage in high-risk patients. © American Journal of Hypertension, Ltd 2015. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Clinical determinants and consequences of left ventricular hypertrophy.

PubMed

Messerli, F H

1983-09-26

The left ventricle adapts to an increased afterload such as that produced by arterial hypertension with concentric left ventricular hypertrophy. However, this adaptive process can be modified by a variety of physiologic and pathophysiologic states. Progressive aging, black race, and perhaps disorders with an increased sympathetic outflow seem to accelerate left ventricular hypertrophy. Obesity and other high cardiac output states predominantly produce dilatation of the left ventricle, and their combination with arterial hypertension results in eccentric left ventricular hypertrophy. Similarly, endurance exercise increases left ventricular volume more than wall thickness, whereas isometric exercise produces an increase in wall thickness only. The presence or absence of some physiologic and pathogenetic factors has direct implication on the assessment of what constitutes a "normal" left ventricular structure and function. Left ventricular hypertrophy has been shown to increase ventricular ectopic impulse generation and to put patients at a high risk of sudden death. Moreover, the increase in myocardial mass lowers coronary reserve and enhances cardiac oxygen requirements. Thus, the presence of left ventricular hypertrophy has to be considered as an ominous sign rather than as a benign adaptive process.

A centrally mediated prolonged hypotension produced by oxotremorine or pilocarpine

PubMed Central

Dage, R.C.

1979-01-01

1 Oxotremorine, methyloxotremorine, pilocarpine or arecoline were given intravenously to anaesthetized cats, dogs or rats, and intraperitoneally to conscious normotensive and spontaneously hypertensive rats, pretreated with doses of methylatropine that completely blocked peripheral muscarinic receptors, to ascertain their effects on blood pressure and heart rate. 2 Oxotremorine but not methyloxotremorine produced a prolonged hypotension in cats and dogs but not in rats. Heart rate was not changed. Pilocarpine, although less potent, produced an identical effect, whereas the effect of arecoline was short by comparison. The hypotensive effect of these drugs was reversed by atropine. 3 In dogs, oxotremorine produced a prolonged hypotension with no change in heart rate or cardiac output. 4 A decrease in spontaneous sympathetic nerve activity accompanied the hypotension in cats. Both effects were reversed by atropine but could be reinvoked by large doses of oxotremorine. 5 The oxotremorine-induced hypotension in cats was not altered by decerebration but was abolished by high cervical spinal section. 6 The results indicate that the prolonged hypotension elicited by oxotremorine is mediated by an action at muscarinic receptors in the brain stem resulting in a decrease in sympathetic nerve activity and peripheral resistance but not heart rate or cardiac output. PMID:760887

Cardiac sympathetic innervation assessed with (123)I-MIBG retains prognostic utility in diabetic patients with severe left ventricular dysfunction evaluated for primary prevention implantable cardioverter-defibrillator.

PubMed

García-González, P; Fabregat-Andrés, Ó; Cozar-Santiago, P; Sánchez-Jurado, R; Estornell-Erill, J; Valle-Muñoz, A; Quesada-Dorador, A; Payá-Serrano, R; Ferrer-Rebolleda, J; Ridocci-Soriano, F

2016-01-01

Scintigraphy with iodine-123-metaiodobenzylguanidine ((123)I-MIBG) is a non-invasive tool for the assessment of cardiac sympathetic innervation (CSI) that has proven to be an independent predictor of survival. Recent studies have shown that diabetic patients with heart failure (HF) have a higher deterioration in CSI. It is unknown if (123)I-MIBG has the same predictive value for diabetic and non-diabetic patients with advanced HF. An analysis is performed to determine whether CSI with (123)I-MIBG retains prognostic utility in diabetic patients with HF, evaluated for a primary prevention implantable cardioverter-defibrillator (ICD). Seventy-eight consecutive HF patients (48 diabetic) evaluated for primary prevention ICD implantation were prospectively enrolled and underwent (123)I-MIBG to assess CSI (heart-to-mediastinum ratio - HMR). A Cox proportional hazards multivariate analysis was used to determine the influence of (123)I-MIBG images for prediction of cardiac events in both diabetic and non-diabetic patients. The primary end-point was a composite of arrhythmic event, cardiac death, or admission due to HF. During a mean follow-up of 19.5 [9.3-29.3] months, the primary end-point occurred in 24 (31%) patients. Late HMR was significantly lower in diabetic patients (1.30 vs. 1.41, p=0.014). Late HMR≤1.30 was an independent predictor of cardiac events in diabetic (hazard ratio 4.53; p=0.012) and non-diabetic patients (hazard ratio 12.31; p=0.023). Diabetic patients with HF evaluated for primary prevention ICD show a higher deterioration in CSI than non-diabetics; nevertheless (123)I-MIBG imaging retained prognostic utility for both diabetic and non-diabetic patients. Copyright © 2015 Elsevier España, S.L.U. and SEMNIM. All rights reserved.

Interacting influences of gender and chronic pain status on parasympathetically mediated heart rate variability in adolescents and young adults.

PubMed

Walker, Lynn S; Stone, Amanda L; Smith, Craig A; Bruehl, Stephen; Garber, Judy; Puzanovova, Martina; Diedrich, André

2017-08-01

Considerable research links chronic pain to autonomic nervous system (ANS) dysfunction, specifically low heart rate variability (HRV) mediated by reduced parasympathetic activity. However, little is known about factors that influence ANS function in chronic pain. The ANS is the primary pathway for brain-gut communication, making it of particular interest in gastrointestinal disorders, such as irritable bowel syndrome, characterized by functional abdominal pain (FAP). We evaluated the relation of sex, pain severity, and psychological stress to ANS function in adolescents/young adults from a database of pediatric FAP and control participants enrolled 8 years earlier in a prospective study of pain. At follow-up in adolescence/young adulthood (Mean age = 19.46, SD = 3.48), we classified participants as Pain-Remit (n = 130), Pain-Persist (n = 96), and pain-free controls (n = 123). We recorded electrocardiogram data at rest and during laboratory stressors. Results demonstrated significantly lower HRV in Pain-Persist females compared with Pain-Remit females, female controls, and all males regardless of pain category. Spectral analysis of electrocardiogram showed that Pain-Persist females had reduced power in the high frequency domain of cardiac activity, ie, reduced parasympathetic "braking" of sympathetic activity, both at rest and during stress. Pain-Remit females exhibited levels of autonomic imbalance intermediate between those of females with persistent FAP and all other participants. Parasympathetically mediated low HRV in young women with persistent FAP may reflect a peripheral mechanism (eg, gut dysfunction) or a central nervous system mechanism (eg, pain amplification or poor emotion self-regulation) involving prolonged sympathetic activation.

Impaired neural structure and function contributing to autonomic symptoms in congenital central hypoventilation syndrome.

PubMed

Harper, Ronald M; Kumar, Rajesh; Macey, Paul M; Harper, Rebecca K; Ogren, Jennifer A

2015-01-01

Congenital central hypoventilation syndrome (CCHS) patients show major autonomic alterations in addition to their better-known breathing deficiencies. The processes underlying CCHS, mutations in the PHOX2B gene, target autonomic neuronal development, with frame shift extent contributing to symptom severity. Many autonomic characteristics, such as impaired pupillary constriction and poor temperature regulation, reflect parasympathetic alterations, and can include disturbed alimentary processes, with malabsorption and intestinal motility dyscontrol. The sympathetic nervous system changes can exert life-threatening outcomes, with dysregulation of sympathetic outflow leading to high blood pressure, time-altered and dampened heart rate and breathing responses to challenges, cardiac arrhythmia, profuse sweating, and poor fluid regulation. The central mechanisms contributing to failed autonomic processes are readily apparent from structural and functional magnetic resonance imaging studies, which reveal substantial cortical thinning, tissue injury, and disrupted functional responses in hypothalamic, hippocampal, posterior thalamic, and basal ganglia sites and their descending projections, as well as insular, cingulate, and medial frontal cortices, which influence subcortical autonomic structures. Midbrain structures are also compromised, including the raphe system and its projections to cerebellar and medullary sites, the locus coeruleus, and medullary reflex integrating sites, including the dorsal and ventrolateral medullary nuclei. The damage to rostral autonomic sites overlaps metabolic, affective and cognitive regulatory regions, leading to hormonal disruption, anxiety, depression, behavioral control, and sudden death concerns. The injuries suggest that interventions for mitigating hypoxic exposure and nutrient loss may provide cellular protection, in the same fashion as interventions in other conditions with similar malabsorption, fluid turnover, or hypoxic exposure.

ECG during helicopter underwater escape training.

PubMed

Tipton, Michael J; Gibbs, Peter; Brooks, Chris; Roiz de Sa, Dan; Reilly, Tara J

2010-04-01

Coincidental stimulation of the sympathetic and parasympathetic nervous system can cause "autonomic conflict" and consequent cardiac arrhythmias. The present study tested the hypotheses that: 1) cardiac arrhythmias would be seen in those undertaking helicopter underwater escape training (HUET); 2) the occurrence of arrhythmias in individuals could be predicted; and 3) the heart rate response to HUET would habituate with repeated runs. There were 26 male volunteers who each undertook 5 HUET submersions into water at 29.5 degrees C, with each run separated by 10 min. Each submersion included a 3-min, 40-s pre-submersion period, a 10-s submersion, and 40-s post-submersion period. Participants wore a three-lead telemetric ECG system beneath an immersion suit and underclothing. Skin temperature was measured in one participant. Each participant undertook tests to establish their autonomic function, including heart rate variability, face immersion, cold pressor test, and aerobic capacity assessment. The heart rate response to HUET was reduced by the fourth run when compared to the first run. Across all runs, 32 cardiac arrhythmias were identified (25%) in 22 different participants; all but 6 of the arrhythmias occurred just after submersion. Only aerobic fitness appeared inversely associated with the occurrence of arrhythmias. The heart rate response to HUET habituates. HUET produces cardiac arrhythmias; these are asymptomatic and probably of little clinical significance in young, fit individuals. It remains to be seen if this is the case with either an older, less fit cohort of people or in those undertaking longer breath holds in colder water.

Cardiac autonomic neuropathy in patients with diabetes mellitus

PubMed Central

Dimitropoulos, Gerasimos; Tahrani, Abd A; Stevens, Martin J

2014-01-01

Cardiac autonomic neuropathy (CAN) is an often overlooked and common complication of diabetes mellitus. CAN is associated with increased cardiovascular morbidity and mortality. The pathogenesis of CAN is complex and involves a cascade of pathways activated by hyperglycaemia resulting in neuronal ischaemia and cellular death. In addition, autoimmune and genetic factors are involved in the development of CAN. CAN might be subclinical for several years until the patient develops resting tachycardia, exercise intolerance, postural hypotension, cardiac dysfunction and diabetic cardiomyopathy. During its sub-clinical phase, heart rate variability that is influenced by the balance between parasympathetic and sympathetic tones can help in detecting CAN before the disease is symptomatic. Newer imaging techniques (such as scintigraphy) have allowed earlier detection of CAN in the pre-clinical phase and allowed better assessment of the sympathetic nervous system. One of the main difficulties in CAN research is the lack of a universally accepted definition of CAN; however, the Toronto Consensus Panel on Diabetic Neuropathy has recently issued guidance for the diagnosis and staging of CAN, and also proposed screening for CAN in patients with diabetes mellitus. A major challenge, however, is the lack of specific treatment to slow the progression or prevent the development of CAN. Lifestyle changes, improved metabolic control might prevent or slow the progression of CAN. Reversal will require combination of these treatments with new targeted therapeutic approaches. The aim of this article is to review the latest evidence regarding the epidemiology, pathogenesis, manifestations, diagnosis and treatment for CAN. PMID:24567799

Evaluation of specific neural marker GAP-43 and TH combined with Masson-trichrome staining for forensic autopsy cases with old myocardial infarction.

PubMed

Yu, Tian-Shui; Wang, Xu; Zhang, Hai-Dong; Bai, Ru-Feng; Zhao, Rui; Guan, Da-Wei

2018-01-01

It has been a puzzling forensic task to determine the cause of death as a result of old myocardial infarction (OMI) in the absence of recognizable acute myocardial infarction. Recent studies indicated that the heterogeneous cardiac nerve sprouting and sympathetic hyperinnervation at border zones of the infarcted site played important roles in sudden cardiac death (SCD). So, the present study explored the value of growth associated protein-43 (GAP-43) and tyrosine hydroxylase (TH) as objective and specific neural biomarkers combined with Masson-trichrome staining for forensic autopsy cases. Myocardium of left ventricle of 58 medicolegal autopsy cases, 12 OMI cases, 12 acute/OMI cases, and 34 control cases, were immunostained with anti-GAP-43 and anti-TH antibodies. Immunoreactivity of GAP-43 and TH identified nerve fibers and vascular wall in OMI cases and acute/OMI cases. Specifically, TH-positive nerve fibers were abundant at border zones of the infarcted site. There were a few GAP-43 and TH expressions in the control cases. With Masson-trichrome staining, collagen fibers were blue and cardiac muscle fibers were pink in marked contrast with the surrounding tissue, which improved the location of nerve fibers. Thus, these findings suggest that immunohistochemical detection of GAP-43 and TH combined with Masson-trichrome staining can provide the evidence for the medicolegal expertise of SCD due to OMI, and further demonstrate a close relationship between sympathetic hyperinnervation and SCD.

Yoga respiratory training improves respiratory function and cardiac sympathovagal balance in elderly subjects: a randomised controlled trial

PubMed Central

Santaella, Danilo F; Devesa, Cesar R S; Rojo, Marcos R; Amato, Marcelo B P; Drager, Luciano F; Casali, Karina R; Montano, Nicola

2011-01-01

Objectives Since ageing is associated with a decline in pulmonary function, heart rate variability and spontaneous baroreflex, and recent studies suggest that yoga respiratory exercises may improve respiratory and cardiovascular function, we hypothesised that yoga respiratory training may improve respiratory function and cardiac autonomic modulation in healthy elderly subjects. Design 76 healthy elderly subjects were enrolled in a randomised control trial in Brazil and 29 completed the study (age 68±6 years, 34% males, body mass index 25±3 kg/m2). Subjects were randomised into a 4-month training program (2 classes/week plus home exercises) of either stretching (control, n=14) or respiratory exercises (yoga, n=15). Yoga respiratory exercises (Bhastrika) consisted of rapid forced expirations followed by inspiration through the right nostril, inspiratory apnoea with generation of intrathoracic negative pressure, and expiration through the left nostril. Pulmonary function, maximum expiratory and inspiratory pressures (PEmax and PImax, respectively), heart rate variability and blood pressure variability for spontaneous baroreflex determination were determined at baseline and after 4 months. Results Subjects in both groups had similar demographic parameters. Physiological variables did not change after 4 months in the control group. However, in the yoga group, there were significant increases in PEmax (34%, p<0.0001) and PImax (26%, p<0.0001) and a significant decrease in the low frequency component (a marker of cardiac sympathetic modulation) and low frequency/high frequency ratio (marker of sympathovagal balance) of heart rate variability (40%, p<0.001). Spontaneous baroreflex did not change, and quality of life only marginally increased in the yoga group. Conclusion Respiratory yoga training may be beneficial for the elderly healthy population by improving respiratory function and sympathovagal balance. Trial Registration CinicalTrials.gov identifier: NCT00969345; trial registry name: Effects of respiratory yoga training (Bhastrika) on heart rate variability and baroreflex, and quality of life of healthy elderly subjects. PMID:22021757

Peak heart rates and sympathetic function in tetraplegic nonathletes and athletes.

PubMed

Currie, Katharine D; West, Christopher R; Hubli, Michéle; Gee, Cameron M; Krassioukov, Andrei V

2015-06-01

To examine differences in peak heart rate (HR) and measures of sympathetic function between nonathletes and athletes with chronic, motor-complete, cervical spinal cord injury (SCI). Eight nonathletic men with SCI (C4-C7; age 47 ± 9 yr, with injury duration of 16 ± 9 yr) and 13 athletic men with SCI (C5-C8; age 37 ± 8 yr, with injury duration of 16 ± 6 yr) participated in the study. Measures of sympathetic function included palmar sympathetic skin responses (SSR) to median nerve stimulation, and systolic (SBP) and diastolic (DBP) blood pressure responses to a passive sit-up test. Peak HR responses were assessed during a maximal exercise test. Compared to the athletic group, the nonathletic group exhibited lower peak HR (102 ± 34 vs 161 ± 20 bpm, P < 0.001) and average SSR scores (0.13 ± 0.35 vs 2.41 ± 1.97, P = 0.008), along with greater reductions in SBP and DBP in response to passive sit-up (SBP: -22 ± 10 vs -9 ± 12 mm Hg, P = 0.019; DBP: -18 ± 8 mm Hg vs -4 ± 9 mm Hg, P = 0.003). On the basis of the criteria for orthostatic hypotension (OH) (drop in SBP ≥ 20 mm Hg or DBP ≥ 10 mm Hg), 88% and 23% of nonathletes and athletes had OH. Attenuated peak HR in nonathletic individuals with tetraplegia may be secondary to impairments in sympathetic function including absent SSR and OH. Furthermore, the degree of preserved sympathetic function documented in tetraplegic athletes may suggest a predisposition to engage in high-performance sports. Collectively, our findings provide novel insight into the importance of the sympathetic nervous system for exercise performance.

Increased Sympathetic and Decreased Parasympathetic Cardiac Tone in Patients with Sleep Related Alveolar Hypoventilation

PubMed Central

Palma, Jose-Alberto; Urrestarazu, Elena; Lopez-Azcarate, Jon; Alegre, Manuel; Fernandez, Secundino; Artieda, Julio; Iriarte, Jorge

2013-01-01

Objective: To assess autonomic function by heart rate variability (HRV) during sleep in patients with sleep related alveolar hypoventilation (SRAH) and to compare it with that of patients with obstructive sleep apnea (OSA) and control patients. Design: Cross-sectional study. Setting: Sleep Unit, University Hospital of University of Navarra. Patients: Fifteen idiopathic and obesity related-SRAH patients were studied. For each patient with SRAH, a patient with OSA, matched in age, sex, body mass index (BMI), minimal oxygen saturation (SatO2), and mean SatO2 was selected. Control patients were also matched in age, sex, and BMI with patients with OSA and those with SRAH, and in apnea/hypopnea index (AHI) with patients with SRAH. Interventions: N/A. Measurements and Results: Time- and frequency-domain HRV measures (R-R, standard deviation of normal-to-normal RR interval [SDNN], very low frequency [VLF], low frequency [LF], high frequency [HF], LF/HF ratio) were calculated across all sleep stages as well as during wakefulness just before and after sleep during a 1-night polysomnography. In patients with SRAH and OSA, LF was increased during rapid eye movement (REM) when compared with control patients, whereas HF was decreased during REM and N1-N2 sleep stages. The LF/HF ratio was equally increased in patients with SRAH and OSA during REM and N1-N2. Correlation analysis showed that LF and HF values during REM sleep were correlated with minimal SatO2 and mean SatO2. Conclusions: Patients with SRAH exhibited an abnormal cardiac tone during sleep. This fact appears to be related to the severity of nocturnal oxygen desaturation. Moreover, there were no differences between OSA and SRAH, supporting the hypothesis that autonomic changes in OSA are primarily related to a reduced nocturnal oxygen saturation, rather than a consequence of other factors such as nocturnal respiratory events. Citation: Palma JA; Urrestarazu E; Lopez-Azcarate J; Alegre M; Fernandez S; Artieda J; Iriarte J. Increased sympathetic and decreased parasym-pathetic cardiac tone in patients with sleep related alveolar hypoventilation. SLEEP 2013;36(6):933-940. PMID:23729937

Contribution of the autonomic nervous system to blood pressure and heart rate variability changes in early experimental hyperthyroidism.

PubMed

Safa-Tisseront, V; Ponchon, P; Laude, D; Elghozi, J L

1998-07-10

A great deal of uncertainty persists regarding the exact nature of the interaction between autonomic nervous system activity and thyroid hormones in the control of heart rate and blood pressure. We now report on thyrotoxicosis produced by daily intraperitoneal (i.p.) injection of L-thyroxine (0.5 mg/kg body wt. in 1 ml of 5 mM NaOH for 5 days). Control rats received i.p. daily injections of the thyroxine solvent. In order to estimate the degree of autonomic activation in hyperthyroidism, specific blockers were administered intravenously: atropine (0.5 mg/kg), prazosin (1 mg/kg), atenolol (1 mg/kg) or the combination of atenolol and atropine. A jet of air was administered in other animals to induce sympathoactivation. Eight animals were studied in each group. The dose and duration of L-thyroxine treatment was sufficient to induce a significant degree of hyperthyroidism with accompanying tachycardia, systolic blood pressure elevation, increased pulse pressure, cardiac hypertrophy, weight loss, tachypnea and hyperthermia. In addition, the intrinsic heart period observed after double blockade (atenolol + atropine) was markedly decreased after treatment with L-thyroxine (121.5+/-3.6 ms vs. 141.2+/-3.7 ms, P < 0.01). Of the autonomic indices, vagal tone (difference between heart period obtained after atenolol and intrinsic heart period) was negatively linearly related to intrinsic heart period (r = 0.71, P < 0.05). Atenolol modified neither the heart period nor blood pressure variability in rats with hyperthyroidism and in these rats the jet of air did not significantly affect the heart period level. The thyrotoxicosis was associated with a reduction of the 0.4 Hz component of blood pressure variability (analyses on 102.4 s segments, modulus 1.10+/-0.07 vs. 1.41+/-0.06 mm Hg, P < 0.01) and prazosin was without effect on this 0.4 Hz component in these animals. These data show a functional diminution of the vascular and cardiac sympathetic tone in early experimental hyperthyroidism. The marked rise in the intrinsic heart rate could be the main determinant of tachycardia. The blood pressure elevation may reflexly induce vagal activation and sympathetic (vascular and cardiac) inhibition.

Pyridostigmine prevents peripheral vascular endothelial dysfunction in rats with myocardial infarction.

PubMed

Qin, Fangfang; Lu, Yi; He, Xi; Zhao, Ming; Bi, Xueyuan; Yu, Xiaojiang; Liu, Jinjun; Zang, Weijin

2014-03-01

1. Myocardial infarction (MI) is characterized by the withdrawal of vagal activity and increased sympathetic activity. We have shown previously that pyridostigmine (PYR), an acetylcholinesterase inhibitor, was able to improve vagal activity and ameliorate cardiac dysfunction following MI. However, the effect of PYR on endothelial dysfunction in peripheral arteries after MI remains unclear. 2. In the present study, MI was induced by coronary artery ligation in adult Sprague-Dawley rats. Rats were treated intragastrically with saline or PYR (approximately 31 mg/kg per day) for 2 weeks, at which time haemodynamic and parasympathetic parameters and the vascular reactivity of isolated mesenteric arteries were measured and the ultrastructure of the endothelium evaluated. 3. Compared with the MI group, PYR not only improved cardiac function, vagal nerve activity and endothelial impairment, but also reduced intravascular superoxide anion and malondialdehyde. In addition, in the PYR-treated MI group, nitric oxide (NO) bioavailability was increased and attenuated endothelium-dependent relaxations were improved, whereas restored vasodilator responses were inhibited by N(G)-nitro-L-arginine methyl ester. 4. Based on our results, PYR is able to attenuate the impairment of peripheral endothelial function and maintain endothelial ultrastructural integrity in MI rats by inhibiting reactive oxygen species production, enhancing NO bioavailability and improving vagal activity. © 2014 Wiley Publishing Asia Pty Ltd.

The cardiac sympathetic co-transmitter galanin reduces acetylcholine release and vagal bradycardia: Implications for neural control of cardiac excitability

PubMed Central

Herring, Neil; Cranley, James; Lokale, Michael N.; Li, Dan; Shanks, Julia; Alston, Eric N.; Girard, Beatrice M.; Carter, Emma; Parsons, Rodney L.; Habecker, Beth A.; Paterson, David J.

2012-01-01

The autonomic phenotype of congestive cardiac failure is characterised by high sympathetic drive and impaired vagal tone, which are independent predictors of mortality. We hypothesize that impaired bradycardia to peripheral vagal stimulation following high-level sympathetic drive is due to sympatho-vagal crosstalk by the adrenergic co-transmitters galanin and neuropeptide-Y (NPY). Moreover we hypothesize that galanin acts similarly to NPY by reducing vagal acetylcholine release via a receptor mediated, protein kinase-dependent pathway. Prolonged right stellate ganglion stimulation (10 Hz, 2 min, in the presence of 10 μM metoprolol) in an isolated guinea pig atrial preparation with dual autonomic innervation leads to a significant (p < 0.05) reduction in the magnitude of vagal bradycardia (5 Hz) maintained over the subsequent 20 min (n = 6). Immunohistochemistry demonstrated the presence of galanin in a small number of tyrosine hydroxylase positive neurons from freshly dissected stellate ganglion tissue sections. Following 3 days of tissue culture however, most stellate neurons expressed galanin. Stellate stimulation caused the release of low levels of galanin and significantly higher levels of NPY into the surrounding perfusate (n = 6, using ELISA). The reduction in vagal bradycardia post sympathetic stimulation was partially reversed by the galanin receptor antagonist M40 after 10 min (1 μM, n = 5), and completely reversed with the NPY Y2 receptor antagonist BIIE 0246 at all time points (1 μM, n = 6). Exogenous galanin (n = 6, 50–500 nM) also reduced the heart rate response to vagal stimulation but had no effect on the response to carbamylcholine that produced similar degrees of bradycardia (n = 6). Galanin (500 nM) also significantly attenuated the release of 3H-acetylcholine from isolated atria during field stimulation (5 Hz, n = 5). The effect of galanin on vagal bradycardia could be abolished by the galanin receptor antagonist M40 (n = 5). Importantly the GalR1 receptor was immunofluorescently co-localised with choline acetyl-transferase containing neurons at the sinoatrial node. The protein kinase C inhibitor calphostin (100 nM, n = 6) abolished the effect of galanin on vagal bradycardia whilst the protein kinase A inhibitor H89 (500 nM, n = 6) had no effect. These results demonstrate that prolonged sympathetic activation releases the slowly diffusing adrenergic co-transmitter galanin in addition to NPY, and that this contributes to the attenuation in vagal bradycardia via a reduction in acetylcholine release. This effect is mediated by GalR1 receptors on vagal neurons coupled to protein kinase C dependent signalling pathways. The role of galanin may become more important following an acute injury response where galanin expression is increased. PMID:22172449

The effect of garden designs on mood and heart output in older adults residing in an assisted living facility.

PubMed

Goto, Seiko; Park, Bum-Jin; Tsunetsugu, Yuko; Herrup, Karl; Miyazaki, Yoshifumi

2013-01-01

The objective of this study is to trace short-term changes in mood and heart function in elderly individuals in response to exposure to different landscaped spaces. Nineteen elderly but cognitively intact residents of an assisted living facility participated in the study. They were exposed to three landscaped spaces: a Japanese style garden, an herb garden, and a simple landscaped area planted with a single tree. To assess the effect of different landscaped spaces on older adults, individuals were monitored for mood and cardiac function in response to short exposures to spaces. Mood state was assessed using Profile of Mood States (POMS) before and after viewing the spaces. Cardiac output was assessed using a portable electrocardiograph monitor before and during the viewing. We found that the structured gardens evoked greater responses in all outcome measures. Scores on the POMS improved after observation of the two organized gardens compared to responses to the simple landscaped space with a single tree. During the observation period, heart rate was significantly lower in the Japanese garden than in the other environments, and sympathetic function was significantly lower as well. We conclude that exposure to organized gardens can affect both the mood and cardiac physiology of elderly individuals. Our data further suggest that these effects can differ depending on the types of landscape to which an individual is exposed. Elderly, Japanese garden, herb garden, heart rate, mood, healing environmentPreferred Citation: Goto, S., Park, B-J., Tsunetsugu, Y., Herrup, K., & Miyazaki, Y. (2013). The effect of garden designs on mood and heart output in older adults residing in an assisted living facility. Health Environments Research & Design Journal 6(2), pp 27-42.

Effects of manual lymph drainage on cardiac autonomic tone in healthy subjects.

PubMed

Kim, Sung-Joong; Kwon, Oh-Yun; Yi, Chung-Hwi

2009-01-01

This study was designed to investigate the effects of manual lymph drainage on the cardiac autonomic tone. Thirty-two healthy male subjects were randomly assigned to manual lymph drainage (MLD) (experimental) and rest (control) groups. Electrocardiogram (ECG) parameters were recorded with bipolar electrocardiography using standard limb lead positions. The pressure-pain threshold (PPT) was quantitatively measured using an algometer. Heart rate variability differed significantly between the experimental and control groups (p < 0.05), but the PPT in the upper trapezius muscle did not (p > 0.05). These findings indicate that the application of MLD was effective in reducing the activity of the sympathetic nervous system.

Differentiation of vasoactive renal sympathetic nerve fibres.

PubMed

Dibona, G F

2000-01-01

Activation of renal sympathetic nerves produces marked changes in renal haemodynamics, tubular ion and water transport and renin secretion. This review examines information indicating that these effects are mediated by functionally specific groups of renal sympathetic nerve fibres separately innervating the renal vessels, tubules and juxtaglomerular granular cells.

Role of neuropeptide Y in renal sympathetic vasoconstriction: studies in normal and congestive heart failure rats.

PubMed

DiBona, G F; Sawin, L L

2001-08-01

Sympathetic nerve activity, including that in the kidney, is increased in heart failure with increased plasma concentrations of norepinephrine and the vasoconstrictor cotransmitter neuropeptide Y (NPY). We examined the contribution of NPY to sympathetically mediated alterations in kidney function in normal and heart failure rats. Heart failure rats were created by left coronary ligation and myocardial infarction. In anesthetized normal rats, the NPY Y(1) receptor antagonist, H 409/22, at two doses, had no effect on heart rate, arterial pressure, or renal hemodynamic and excretory function. In conscious severe heart failure rats, high-dose H 409/22 decreased mean arterial pressure by 8 +/- 2 mm Hg but had no effect in normal and mild heart failure rats. During graded frequency renal sympathetic nerve stimulation (0 to 10 Hz), high-dose H 409/22 attenuated the decreases in renal blood flow only at 10 Hz (-36% +/- 5%, P <.05) in normal rats but did so at both 4 (-29% +/- 4%, P <.05) and 10 Hz (-33% +/- 5%, P <.05) in heart failure rats. The glomerular filtration rate, urinary flow rate, and sodium excretion responses to renal sympathetic nerve stimulation were not affected by high-dose H 409/22 in either normal or heart failure rats. NPY does not participate in the regulation of kidney function and arterial pressure in normal conscious or anesthetized rats. When sympathetic nervous system activity is increased, as in heart failure and intense renal sympathetic nerve stimulation, respectively, a small contribution of NPY to maintenance of arterial pressure and to sympathetic renal vasoconstrictor responses may be identified.

Effects of Escitalopram on Autonomic Function in Posttraumatic Stress Disorder Among Veterans of Operations Enduring Freedom and Iraqi Freedom (OEF/OIF).

PubMed

Ramaswamy, Sriram; Selvaraj, Vithyalakshmi; Driscoll, David; Madabushi, Jayakrishna S; Bhatia, Subhash C; Yeragani, Vikram

2015-01-01

Posttraumatic stress disorder is a chronic, debilitating condition that has become a growing concern among combat veterans. Previous research suggests that posttraumatic stress disorder disrupts normal autonomic responding and may increase the risk of cardiovascular disease and mortality. Measures of heart rate variability and QT interval variability have been used extensively to characterize sympathetic and parasympathetic influences on heart rate in a variety of psychiatric populations. The objective of this study was to better understand the effects of pharmacological treatment on autonomic reactivity in posttraumatic stress disorder. A 12-week, Phase IV, prospective, open-label trial of escitalopram in veterans with combat-related posttraumatic stress disorder and comorbid depression. An outpatient mental health clinic at a Veterans Affairs Medical Center. Eleven male veterans of Operations Enduring Freedom and Iraqi Freedom diagnosed with posttraumatic stress disorder and comorbid depression. Autonomic reactivity was measured by examining heart rate variability and QT interval variability. Treatment safety and efficacy were also evaluated pre- and post-treatment. We observed a reduction in posttraumatic stress disorder and depression symptoms from pre- to post-treatment, and escitalopram was generally well tolerated in our sample. In addition, we observed a decrease in high frequency heart rate variability and an increase in QT variability, indicating a reduction in cardiac vagal function and heightened sympathetic activation. These findings suggest that escitalopram treatment in patients with posttraumatic stress disorder and depression can trigger changes in autonomic reactivity that may adversely impact cardiovascular health.

Cardiovascular dysfunction following spinal cord injury

PubMed Central

Partida, Elizabeth; Mironets, Eugene; Hou, Shaoping; Tom, Veronica J.

2016-01-01

Both sensorimotor and autonomic dysfunctions often occur after spinal cord injury (SCI). Particularly, a high thoracic or cervical SCI interrupts supraspinal vasomotor pathways and results in disordered hemodynamics due to deregulated sympathetic outflow. As a result of the reduced sympathetic activity, patients with SCI may experience hypotension, cardiac dysrhythmias, and hypothermia post-injury. In the chronic phase, changes within the CNS and blood vessels lead to orthostatic hypotension and life-threatening autonomic dysreflexia (AD). AD is characterized by an episodic, massive sympathetic discharge that causes severe hypertension associated with bradycardia. The syndrome is often triggered by unpleasant visceral or sensory stimuli below the injury level. Currently the only treatments are palliative – once a stimulus elicits AD, pharmacological vasodilators are administered to help reduce the spike in arterial blood pressure. However, a more effective means would be to mitigate AD development by attenuating contributing mechanisms, such as the reorganization of intraspinal circuits below the level of injury. A better understanding of the neuropathophysiology underlying cardiovascular dysfunction after SCI is essential to better develop novel therapeutic approaches to restore hemodynamic performance. PMID:27073353

Orthostatic intolerance: potential pathophysiology and therapy.

PubMed

Lu, Chih-Cherng; Tseng, Ching-Jiunn; Tang, Hung-Shang; Tung, Che-Se

2004-09-30

Orthostatic intolerance affects an estimated 1 in 500 persons and causes a wide range of disabilities. After essential hypertension, it is the most frequently encountered dysautonomia, accounting for the majority of patients referred to centers specializing in autonomic disorders. Patients are typically young females with symptoms such as dizziness, visual changes, head and neck discomfort, poor concentration, fatigue, palpitations, tremulousness, anxiety, and, in some cases, syncope. Syncope is the most hazardous symptom of orthostatic intolerance, presumably occurring because of impaired cerebral perfusion and in part to compensatory autonomic mechanisms. The etiology of this syndrome is still unclear but is heterogeneous. Orthostatic intolerance used to be characterized by an overall enhancement of noradrenergic tone at rest in some patients and by a patchy dysautonomia of postganglionic sympathetic fibers with a compensatory cardiac sympathetic activation in others. However, recent advances in molecular genetics are improving our understanding of orthostatic intolerance, such as several genetic diseases (such as Ehler-Danlos syndrome and norepinephrine transporter deficiency) presenting with symptoms typical of orthostatic intolerance. Future work will include investigation of genetic functional mutations underlying interindividual differences in autonomic cardiovascular control, body fluid regulation, and vascular regulation in orthostatic intolerance patients. The goal of this review article is to describe recent advances in understanding the pathophysiological mechanisms of orthostatic intolerance and their clinical significance.

Long commuting time, extensive overtime, and sympathodominant state assessed in terms of short-term heart rate variability among male white-collar workers in the Tokyo megalopolis.

PubMed

Kageyama, T; Nishikido, N; Kobayashi, T; Kurokawa, Y; Kaneko, T; Kabuto, M

1998-07-01

To investigate the possible effects of long commuting time and extensive overtime on daytime cardiac autonomic activity, the short-term heart rate variability (HRV) both at supine rest and at standing rest of 223 male white-collar workers in the Tokyo Megalopolis was examined. Workers with a one-way commute of 90 min or more exhibited decreased vagal activity at supine rest and increased sympathetic activity regardless of posture, and those doing overtime of 60 h/month or more exhibited decreased vagal activity and increased sympathetic activity at standing rest. These findings suggest that chronic stress or fatigue resulting from long commuting time or extensive overtime caused these individuals to be in a sympathodominant state. Although these shifts in autonomic activities are not direct indicators of disease, it can be hypothesized that they can induce cardiovascular abnormalities or dysfunctions related to the onset of heart disease. Assessment of the daily and weekly variations in HRV as a function of daily life activities (such as working, commuting, sleeping, and exercising) among workers in Asia-Pacific urban areas might be one way of studying the possible effects of long commuting time, and extensive overtime, on health.

[Remodeling of Cardiovascular System: Causes and Consequences].

PubMed

Lopatina, E V; Kipenko, A V; Penniyaynen, V A; Pasatetckaia, N A; Tsyrline, V A

2016-01-01

Literature and our data suggest the regulatory action of a number of biologically active substances (catecholamines, cardiac glycosides, β-blockers, angiotensin-converting-enzyme inhibitor) on the growth and proliferation of heart cells. By using of organotypic tissue culture has proved that the basis of this regulation is the ability of test substances, receptor- or transducer-mediated signaling to modulate the function of Na⁺, K⁺-ATPase. There is a delay in the development of vascular smooth muscle in the late postnatal period in rats with the blockade of the sympathetic nervous system in the prenatal period. The relationship between vascular remodeling and contractile activity is described. It seems that one of the causes of high blood pressure is a remodeling of the cardiovascular system, which precedes the development of hypertension.

Linear and Nonlinear Analyses of the Cardiac Autonomic Control in Children With Developmental Coordination Disorder: A Case-Control Study.

PubMed

Cavalcante Neto, Jorge L; Zamunér, Antonio R; Moreno, Bianca C; Silva, Ester; Tudella, Eloisa

2018-01-01

Children with Developmental Coordination Disorder (DCD) and children at risk for DCD (r-DCD) present motor impairments interfering in their school, leisure and daily activities. In addition, these children may have abnormalities in their cardiac autonomic control, which together with their motor impairments, restrict their health and functionality. Therefore, this study aimed to assess the cardiac autonomic control, by linear and nonlinear analysis, at supine and during an orthostatic stimulus in DCD, r-DCD and typically developed children. Thirteen DCD children (11 boys and 2 girls, aged 8.08 ± 0.79 years), 19 children at risk for DCD (13 boys and 6 girls, aged 8.10 ± 0.96 years) and 18 typically developed children, who constituted the control group (CG) (10 boys and 8 girls, aged 8.50 ± 0.96 years) underwent a heart rate variability (HRV) examination. R-R intervals were recorded in order to assess the cardiac autonomic control using a validated HR monitor. HRV was analyzed by linear and nonlinear methods and compared between r-DCD, DCD, and CG. The DCD group presented blunted cardiac autonomic adjustment to the orthostatic stimulus, which was not observed in r-DCD and CG. Regarding nonlinear analysis of HRV, the DCD group presented lower parasympathetic modulation in the supine position compared to the r-DCD and CG groups. In the within group analysis, only the DCD group did not increase HR from supine to standing posture. Symbolic analysis revealed a significant decrease in 2LV ( p < 0.0001) and 2UV ( p < 0.0001) indices from supine to orthostatic posture only in the CG. In conclusion, r-DCD and DCD children present cardiac autonomic dysfunction characterized by higher sympathetic, lower parasympathetic and lower complexity of cardiac autonomic control in the supine position, as well as a blunted autonomic adjustment to the orthostatic stimulus. Therefore, cardiovascular health improvement should be part of DCD children's management, even in cases of less severe motor impairment.

Moxonidine-induced central sympathoinhibition improves prognosis in rats with hypertensive heart failure.

PubMed

Honda, Nobuhiro; Hirooka, Yoshitaka; Ito, Koji; Matsukawa, Ryuichi; Shinohara, Keisuke; Kishi, Takuya; Yasukawa, Keiji; Utsumi, Hideo; Sunagawa, Kenji

2013-11-01

Enhanced central sympathetic outflow is an indicator of the prognosis of heart failure. Although the central sympatholytic drug moxonidine is an established therapeutic strategy for hypertension, its benefits for hypertensive heart failure are poorly understood. In the present study, we investigated the effects of central sympathoinhibition by intracerebral infusion of moxonidine on survival in a rat model of hypertensive heart failure and the possible mechanisms involved. As a model of hypertensive heart failure, we fed Dahl salt-sensitive rats an 8% NaCl diet from 7 weeks of age. Intracerebroventricular (ICV) infusion of moxonidine (moxonidine-ICV-treated group [Mox-ICV]) or vehicle (vehicle-ICV-treated group [Veh-ICV]) was performed at 14-20 weeks of age, during the increased heart failure phase. Survival rates were examined, and sympathetic activity, left ventricular function and remodelling, and brain oxidative stress were measured. Hypertension and left ventricular hypertrophy were established by 13 weeks of age. At around 20 weeks of age, Veh-ICV rats exhibited overt heart failure concomitant with increased urinary norepinephrine (uNE) excretion as an index of sympathetic activity, dilated left ventricle, decreased percentage fractional shortening, and myocardial fibrosis. Survival rates at 21 weeks of age (n = 28) were only 23% in Veh-ICV rats, and 76% (n = 17) in Mox-ICV rats with concomitant decreases in uNE, myocardial fibrosis, collagen type I/III ratio, brain oxidative stress, and suppressed left ventricular dysfunction. Moxonidine-induced central sympathoinhibition attenuated brain oxidative stress, prevented cardiac dysfunction and remodelling, and improved the prognosis in rats with hypertensive heart failure. Central sympathoinhibition can be effective for the treatment of hypertensive heart failure.

Emotion regulation and heterogeneity in attention-deficit/hyperactivity disorder.

PubMed

Musser, Erica D; Galloway-Long, Hilary S; Frick, Paul J; Nigg, Joel T

2013-02-01

How best to capture heterogeneity in attention-deficit/hyperactivity disorder (ADHD) using biomarkers has been elusive. This study evaluated whether emotion reactivity and regulation provide a means to achieve this. Participants were classified into three groups: children with ADHD plus low prosocial behavior (hypothesized to be high in callous/unemotional traits; n = 21); children with ADHD with age-appropriate prosocial behavior (n = 54); and typically developing children (n = 75). Children completed a task with four conditions: negative induction, negative suppression, positive induction, and positive suppression of affect. The task required children to view an emotion-laden film clip, while either facially mimicking (induction) or masking (suppression) the emotion of the main character. Parasympathetic and sympathetic nervous system activity were assessed via respiratory sinus arrhythmia (RSA) and cardiac pre-ejection period (PEP), respectively. Symptoms of anxiety, conduct, and oppositional defiant disorders were treated as covariates. The ADHD-typical-prosocial group displayed atypically elevated parasympathetic reactivity (emotion dysregulation) during positive induction, along with increased sympathetic activity (elevated arousal) across conditions. In contrast, the ADHD-low-prosocial group displayed reduced parasympathetic reactivity and reduced sympathetic activity (low emotional arousal) across baseline and task conditions. Thus, both ADHD groups had altered patterns of autonomic functioning, but in two distinct forms. Although ADHD is heterogeneous clinically, results suggest that ADHD is also heterogeneous with regard to physiological indices of emotion and regulation. Future studies of emotion, regulation, and ADHD should take this into account. Further study of physiological responding in ADHD may yield clinically and etiologically distinct domains or groups. Copyright © 2013 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

Intersections between cardiac physiology, emotion regulation and interpersonal warmth in preschoolers: Implications for drug abuse prevention from translational neuroscience.

PubMed

Clark, Caron A C; Skowron, Elizabeth A; Giuliano, Ryan J; Fisher, Philip A

2016-06-01

Early childhood is characterized by dramatic gains in emotion regulation skills that support social adjustment and mental health. Understanding the physiological substrates of healthy emotion regulation may offer new directions for altering trajectories toward initiation and escalation of substance abuse. Here, we describe the intersections between parasympathetic and sympathetic tone, emotion regulation and prosocial behavior in a high-risk sample of preschoolers. Fifty-two 3-6 year old children completed an assessment of attention regulation in response to affective stimuli. Cardiac respiratory sinus arrhythmia, an index of parasympathetic tone, and pre-ejection period, a marker of sympathetic activation, were recorded at rest and while children engaged in social interactions with their mothers and an unfamiliar research assistant. Mothers reported on children's emotional reactivity and prosocial behavior. Controlling for age and psychosocial risk, higher parasympathetic tone predicted better attention regulation in response to angry emotion and higher levels of prosocial behavior, whereas a reciprocal pattern of higher parasympathetic tone and lower sympathetic arousal predicted better attention in response to positive emotion and lower emotional reactivity. Children exposed to fewer risk factors and higher levels of maternal warmth were more able to sustain a high level of parasympathetic tone during interaction episodes. Findings suggest that autonomic measures represent biomarkers for socio-emotional competence in young children. They also point to the importance of early experiences in the establishment of physiological regulation and the promise of family-based intervention to promote healthy emotion regulation and prevent substance dependence in high-risk populations. Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Is Baseline Cardiac Autonomic Modulation Related to Performance and Physiological Responses Following a Supramaximal Judo Test?

PubMed Central

Blasco-Lafarga, Cristina; Martínez-Navarro, Ignacio; Mateo-March, Manuel

2013-01-01

Little research exists concerning Heart Rate (HR) Variability (HRV) following supramaximal efforts focused on upper-body explosive strength-endurance. Since they may be very demanding, it seems of interest to analyse the relationship among performance, lactate and HR dynamics (i.e. HR, HRV and complexity) following them; as well as to know how baseline cardiac autonomic modulation mediates these relationships. The present study aimed to analyse associations between baseline and post-exercise HR dynamics following a supramaximal Judo test, and their relationship with lactate, in a sample of 22 highly-trained male judoists (20.70±4.56 years). A large association between the increase in HR from resting to exercise condition and performance suggests that individuals exerted a greater sympathetic response to achieve a better performance (Rating of Perceived Exertion: 20; post-exercise peak lactate: 11.57±2.24 mmol/L; 95.76±4.13 % of age-predicted HRmax). Athletes with higher vagal modulation and lower sympathetic modulation at rest achieved both a significant larger ∆HR and a faster post-exercise lactate removal. A enhanced resting parasympathetic modulation might be therefore related to a further usage of autonomic resources and a better immediate metabolic recovery during supramaximal exertions. Furthermore, analyses of variance displayed a persistent increase in α1 and a decrease in lnRMSSD along the 15 min of recovery, which are indicative of a diminished vagal modulation together with a sympathovagal balance leaning to sympathetic domination. Eventually, time-domain indices (lnRMSSD) showed no lactate correlations, while nonlinear indices (α1 and lnSaEn) appeared to be moderate to strongly correlated with it, thus pointing to shared mechanisms between neuroautonomic and metabolic regulation. PMID:24205273

Comparing maximum autonomic activity of psychogenic non-epileptic seizures and epileptic seizures using heart rate variability.

PubMed

Jeppesen, Jesper; Beniczky, Sándor; Johansen, Peter; Sidenius, Per; Fuglsang-Frederiksen, Anders

2016-04-01

The semiology of psychogenic non-epileptic seizures (PNES) can resemble epileptic seizures, and differentiation between epileptic seizures with no EEG-correlate and PNES can be challenging even for trained experts. Therefore, there has been a search for a quantitative measure, other than EEG and semiology that could distinguish PNES from epileptic seizures. We used ECG to measure heart rate variability (HRV) in order to compare maximum autonomic activity of epileptic seizures and PNES. These comparisons could potentially serve as biomarkers for distinguishing these types of clinical episodes. Forty-nine epileptic seizures from 17 patients and 24 PNES from 7 patients with analyzable ECG were recorded during long-term video-EEG monitoring. Moving windows of 100 R-R intervals throughout each seizure were used to find maximum values of Cardiac Sympathetic Index (CSI) (sympathetic tonus) and minimum values of Cardiac Vagal Index (CVI), Root-Mean-Square-of-Successive-Differences (RMSSD) and HF-power (parasympathetic tonus). In addition, non-seizure recordings of each patient were used to compare HRV-parameters between the groups. The maximum CSI for epilepsy seizures were higher than PNES (P=0.015). The minimum CVI, minimum RMSSD and HF-power did not show significant difference between epileptic seizures and PNES (P=0.762; P=0.152; P=0.818). There were no statistical difference of non-seizure HRV-parameters between the PNES and epilepsy patients. We found the maximum sympathetic activity accompanying the epileptic seizures to be higher, than that during the PNES. However, the great variation of autonomic response within both groups makes it difficult to use these HRV-measures as a sole measurement in distinguishing epileptic seizures from PNES. Copyright © 2016 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Neural control of renal function.

PubMed

Johns, Edward J; Kopp, Ulla C; DiBona, Gerald F

2011-04-01

The kidney is innervated with efferent sympathetic nerve fibers that directly contact the vasculature, the renal tubules, and the juxtaglomerular granular cells. Via specific adrenoceptors, increased efferent renal sympathetic nerve activity decreases renal blood flow and glomerular filtration rate, increases renal tubular sodium and water reabsorption, and increases renin release. Decreased efferent renal sympathetic nerve activity produces opposite functional responses. This integrated system contributes importantly to homeostatic regulation of sodium and water balance under physiological conditions and to pathological alterations in sodium and water balance in disease. The kidney contains afferent sensory nerve fibers that are located primarily in the renal pelvic wall where they sense stretch. Stretch activation of these afferent sensory nerve fibers elicits an inhibitory renorenal reflex response wherein the contralateral kidney exhibits a compensatory natriuresis and diuresis due to diminished efferent renal sympathetic nerve activity. The renorenal reflex coordinates the excretory function of the two kidneys so as to facilitate homeostatic regulation of sodium and water balance. There is a negative feedback loop in which efferent renal sympathetic nerve activity facilitates increases in afferent renal nerve activity that in turn inhibit efferent renal sympathetic nerve activity so as to avoid excess renal sodium retention. In states of renal disease or injury, there is activation of afferent sensory nerve fibers that are excitatory, leading to increased peripheral sympathetic nerve activity, vasoconstriction, and increased arterial pressure. Proof of principle studies in essential hypertensive patients demonstrate that renal denervation produces sustained decreases in arterial pressure. © 2011 American Physiological Society. Compr Physiol 1:699-729, 2011.

Clinical Implications of Cardiac-MIBG SPECT in the Differentiation of Parkinsonian Syndromes

PubMed Central

Shin, Dong Hoon; Bang, Oh Young; Joo, In Soo; Huh, Kyoon

2006-01-01

Background and Purpose 123I cardiac meta-iodobenzylguanidine (MIBG), an analogue of norepinephrine, has been used to estimate myocardial sympathetic nerve function. We investigate whether cardiac-MIBG SPECT is clinically applicable in the differentiation of Parkinson's disease (PD) from parkinsonian syndromes. Methods Cardiac-MIBG scintigraphy was performed in 27 controls, in 40 patients with PD and in 52 patients with other parkinsonian syndromes comprising 23 with multiple system atrophy (MSA), 26 with drug-induced parkinsonism (DIP), and 3 with corticobasal degeneration (CBD). The heart to mediastinum (H/M) uptake ratio was calculated for each subjects. Patients who either had medical conditions that confused the MIBG SPECT results or who took medications that interfere with MIBG accumulation were excluded from the study. Results Both early and delayed H/M ratios were in patients with PD significantly lower than in controls (early, 1.34±0.15 vs 1.79±0.19; delayed, 1.29±0.15 vs 2.06±0.29, p<0.001). In patients with PD, both early and delayed H/M ratios were significantly lower than those in patients with MSA (early, 1.68±0.23; delayed, 1.80±0.34, p<0.001), DIP (early, 1.83±0.24; delayed, 2.07±0.4, p<0.001), or CBD (early, 1.85±0.01; delayed, 1.99±0.19, p<0.001). Two patients with DIP, who were within the range of patients with PD, showed clinically similar courses of PD. Conclusions This study demonstrates that cardiac-MIBG is a clinically powerful tools to differentiate PD from other parkinsonian syndromes. PMID:20396485

Sympathetic Innervation Promotes Arterial Fate by Enhancing Endothelial ERK Activity.

PubMed

Pardanaud, Luc; Pibouin-Fragner, Laurence; Dubrac, Alexandre; Mathivet, Thomas; English, Isabel; Brunet, Isabelle; Simons, Michael; Eichmann, Anne

2016-08-19

Arterial endothelial cells are morphologically, functionally, and molecularly distinct from those found in veins and lymphatic vessels. How arterial fate is acquired during development and maintained in adult vessels is incompletely understood. We set out to identify factors that promote arterial endothelial cell fate in vivo. We developed a functional assay, allowing us to monitor and manipulate arterial fate in vivo, using arteries isolated from quails that are grafted into the coelom of chick embryos. Endothelial cells migrate out from the grafted artery, and their colonization of host arteries and veins is quantified. Here we show that sympathetic innervation promotes arterial endothelial cell fate in vivo. Removal of sympathetic nerves decreases arterial fate and leads to colonization of veins, whereas exposure to sympathetic nerves or norepinephrine imposes arterial fate. Mechanistically, sympathetic nerves increase endothelial ERK (extracellular signal-regulated kinase) activity via adrenergic α1 and α2 receptors. These findings show that sympathetic innervation promotes arterial endothelial fate and may lead to novel approaches to improve arterialization in human disease. © 2016 American Heart Association, Inc.

Natural and unnatural triggers of myocardial infarction.

PubMed

Kloner, Robert A

2006-01-01

Previous analyses have suggested that factors that stimulate the sympathetic nervous system and catecholamine release can trigger acute myocardial infarction. The wake-up time, Mondays, winter season, physical exertion, emotional upset, overeating, lack of sleep, cocaine, marijuana, anger, and sexual activity are some of the more common triggers. Certain natural disasters such as earthquakes and blizzards have also been associated with an increase in cardiac events. Certain unnatural triggers may play a role including the Holiday season. Holiday season cardiac events peak on Christmas and New Year. A number of hypotheses have been raised to explain the increase in cardiac events during the holidays, including overeating, excessive use of salt and alcohol, exposure to particulates, from fireplaces, a delay in seeking medical help, anxiety or depression related to the holidays, and poorer staffing of health care facilities at this time. War has been associated with an increase in cardiac events. Data regarding an increase in cardiac events during the 9/11 terrorist attack have been mixed. Understanding the cause of cardiovascular triggers will help in developing potential therapies.

Changes of deceleration and acceleration capacity of heart rate in patients with acute hemispheric ischemic stroke.

PubMed

Xu, Yan-Hong; Wang, Xing-De; Yang, Jia-Jun; Zhou, Li; Pan, Yong-Chao

2016-01-01

Autonomic dysfunction is common after stroke, which is correlated with unfavorable outcome. Phase-rectified signal averaging is a newly developed technique for assessing cardiac autonomic function, by detecting sympathetic and vagal nerve activity separately through calculating acceleration capacity (AC) and deceleration capacity (DC) of heart rate. In this study, we used this technique for the first time to investigate the cardiac autonomic function of patients with acute hemispheric ischemic stroke. A 24-hour Holter monitoring was performed in 63 patients with first-ever acute ischemic stroke in hemisphere and sinus rhythm, as well as in 50 controls with high risk of stroke. DC, AC, heart rate variability parameters, standard deviation of all normal-to-normal intervals (SDNN), and square root of the mean of the sum of the squares of differences between adjacent normal-to-normal intervals (RMSSD) were calculated. The National Institutes of Health Stroke Scale (NIHSS) was used to assess the severity of stroke. We analyzed the changes of DC, AC, SDNN, and RMSSD and also studied the correlations between these parameters and NIHSS scores. The R-R (R wave to R wave on electrocardiogram) intervals, DC, AC, and SDNN in the cerebral infarction group were lower than those in controls (P=0.003, P=0.002, P=0.006, and P=0.043), but the difference of RMSSD and the D-value and ratio between absolute value of AC (|AC|) and DC were not statistically significant compared with those in controls. The DC of the infarction group was significantly correlated with |AC|, SDNN, and RMSSD (r=0.857, r=0.619, and r=0.358; P=0.000, P=0.000, and P=0.004). Correlation analysis also showed that DC, |AC|, and SDNN were negatively correlated with NIHSS scores (r=-0.279, r=-0.266, and r=-0.319; P=0.027, P=0.035, and P=0.011). Both DC and AC of heart rate decreased in patients with hemispheric infarction, reflecting a decrease in both vagal and sympathetic modulation. Both DC and AC were correlated with the severity of stroke.

Heritability and Temporal Stability of Ambulatory Autonomic Stress Reactivity in Unstructured 24-Hour Recordings.

PubMed

Neijts, Melanie; van Lien, Rene; Kupper, Nina; Boomsma, Dorret; Willemsen, Gonneke; de Geus, Eco J C

2015-10-01

Measurements of ambulatory autonomic reactivity can help with our understanding of the long-term health consequences of exposure to psychosocial stress in real-life settings. In this study, unstructured 24-hour ambulatory recordings of cardiac parasympathetic and sympathetic control were obtained in 1288 twins and siblings, spanning both work time and leisure time. These data were used to define two ambulatory baseline (sleep, leisure) and four stress conditions (wake, work, work_sitting, work_peak) from which six ambulatory stress reactivity measures were derived. The use of twin families allowed for estimation of heritability and testing for the amplification of existing or emergence of new genetic variance during stress compared with baseline conditions. Temporal stability of ambulatory reactivity was assessed in 62 participants and was moderate to high over a 3-year period (0.36 < r < 0.91). Depending on the definition of ambulatory reactivity used, significant heritability was found, ranging from 29% to 40% for heart rate, 34% to 47% for cardiac parasympathetic control (indexed as respiratory sinus arrhythmia), and 10% to 19% for cardiac sympathetic control (indexed as the preejection period). Heritability of ambulatory reactivity was largely due to newly emerging genetic variance during stress compared with periods of rest. Interestingly, reactivity to short standardized stressors was poorly correlated with the ambulatory reactivity measures implying poor laboratory-real-life correspondence. Ambulatory autonomic reactivity extracted from an unstructured real-life setting shows reliable, stable, and heritable individual differences. Real-life situations uncover a new and different genetic variation compared with that seen in resting baseline conditions, including sleep.

Unraveling of the Effect of Nodose Ganglion Degeneration on the Coronary Artery Vasospasm After Subarachnoid Hemorrhage: An Experimental Study.

PubMed

Yolas, Coskun; Kanat, Ayhan; Aydin, Mehmet Dumlu; Altas, Ender; Kanat, Ilyas Ferit; Kazdal, Hizir; Duman, Aslihan; Gundogdu, Betul; Gursan, Nesrin

2016-02-01

Cardiac arrest is a major life-threatening complication of subarachnoid hemorrhage (SAH). Although medullary cardiocirculatuar center injury and central sympathetic overactivity have been suspected of initiating coronary artery spasm-induced cardiac arrest, we aimed to elucidate the effects of vagal ischemia at the brainstem on coronary vasospasm and sudden death in SAH. Twenty-six rabbits were randomly divided into 3 groups. Control (n = 5); SHAM (n = 8), and SAH group (n = 13). Experimental SAH was applied by injecting homologous blood into the cisterna magna, and the SHAM group was injected with isotonic saline solution also in the cisterna magna., Twenty-one days after the injection, histopathologic changes of the neuron density of nodose ganglia, the vasospasm index values of the coronary arteries, and the electrocardiographic events were analyzed. Increased vasospasm index of the coronary arteries and degenerated neuron density of nodose ganglion were significantly different between animals with SAH, control, and SHAM groups (P < 0.005). If neurons of the nodose ganglia are lesioned due to ischemic insult during SAH, the heart rhythm regulation by vagus afferent reflexes is disturbed. We found that there is causal relationship between nodose ganglion degeneration and coronary vasospasm. Our finding could be the reason that many cardiac events occur in patients with SAH. Vagal pathway paralysis induced by indirect sympathetic overactivity may trigger coronary vasospasm and heart rhythm disturbances. Our findings will aid in the planning of future experimental studies and in determining the clinical relevance of such studies. Copyright © 2016 Elsevier Inc. All rights reserved.

A Sympathetic Neuron Autonomous Role for Egr3-Mediated Gene Regulation in Dendrite Morphogenesis and Target Tissue Innervation

PubMed Central

Quach, David H.; Oliveira-Fernandes, Michelle; Gruner, Katherine A.; Tourtellotte, Warren G.

2013-01-01

Egr3 is a nerve growth factor (NGF)-induced transcriptional regulator that is essential for normal sympathetic nervous system development. Mice lacking Egr3 in the germline have sympathetic target tissue innervation abnormalities and physiologic sympathetic dysfunction similar to humans with dysautonomia. However, since Egr3 is widely expressed and has pleiotropic function, it has not been clear whether it has a role within sympathetic neurons and if so, what target genes it regulates to facilitate target tissue innervation. Here, we show that Egr3 expression within sympathetic neurons is required for their normal innervation since isolated sympathetic neurons lacking Egr3 have neurite outgrowth abnormalities when treated with NGF and mice with sympathetic neuron-restricted Egr3 ablation have target tissue innervation abnormalities similar to mice lacking Egr3 in all tissues. Microarray analysis performed on sympathetic neurons identified many target genes deregulated in the absence of Egr3, with some of the most significantly deregulated genes having roles in axonogenesis, dendritogenesis, and axon guidance. Using a novel genetic technique to visualize axons and dendrites in a subpopulation of randomly labeled sympathetic neurons, we found that Egr3 has an essential role in regulating sympathetic neuron dendrite morphology and terminal axon branching, but not in regulating sympathetic axon guidance to their targets. Together, these results indicate that Egr3 has a sympathetic neuron autonomous role in sympathetic nervous system development that involves modulating downstream target genes affecting the outgrowth and branching of sympathetic neuron dendrites and axons. PMID:23467373

Implantable electrode for recording nerve signals in awake animals

NASA Technical Reports Server (NTRS)

Ninomiya, I.; Yonezawa, Y.; Wilson, M. F.

1976-01-01

An implantable electrode assembly consisting of collagen and metallic electrodes was constructed to measure simultaneously neural signals from the intact nerve and bioelectrical noises in awake animals. Mechanical artifacts, due to bodily movement, were negligibly small. The impedance of the collagen electrodes, measured in awake cats 6-7 days after implantation surgery, ranged from 39.8-11.5 k ohms at a frequency range of 20-5 kHz. Aortic nerve activity and renal nerve activity, measured in awake conditions using the collagen electrode, showed grouped activity synchronous with the cardiac cycle. Results indicate that most of the renal nerve activity was from postganglionic sympathetic fibers and was inhibited by the baroceptor reflex in the same cardiac cycle.

Clinical utility of sympathetic blockade in cardiovascular disease management.

PubMed

Park, Chan Soon; Lee, Hae-Young

2017-04-01

A dysregulated sympathetic nervous system is a major factor in the development and progression of cardiovascular disease; thus, understanding the mechanism and function of the sympathetic nervous system and appropriately regulating sympathetic activity to treat various cardiovascular diseases are crucial. Areas covered: This review focused on previous studies in managing hypertension, atrial fibrillation, coronary artery disease, heart failure, and perioperative management with sympathetic blockade. We reviewed both pharmacological and non-pharmacological management. Expert commentary: Chronic sympathetic nervous system activation is related to several cardiovascular diseases mediated by various pathways. Advancement in measuring sympathetic activity makes visualizing noninvasively and evaluating the activation level even in single fibers possible. Evidence suggests that sympathetic blockade still has a role in managing hypertension and controlling the heart rate in atrial fibrillation. For ischemic heart disease, beta-adrenergic receptor antagonists have been considered a milestone drug to control symptoms and prevent long-term adverse effects, although its clinical implication has become less potent in the era of successful revascularization. Owing to pathologic involvement of sympathetic nervous system activation in heart failure progression, sympathetic blockade has proved its value in improving the clinical course of patients with heart failure.

[Autonomic nervous function in patients with vertigo--evaluation for static function, variation and dynamic change using power spectral analysis of RR intervals].

PubMed

Seki, S

1997-04-01

Power spectral analysis of RR intervals (PSA) of 94 vertiginous patients with associated autonomic nervous dysfunction (AND group), 31 patients with vertebro-basilar insufficiency (VBI group) and 25 controls were analyzed in supine and upright positions. In addition static function, variation from the supine to the upright position and dynamic change in autonomic nervous function (ANF) from the supine to the upright position were examined. Heart rate was recorded for 120 seconds in the supine and 40 seconds in the upright position. RR intervals for each 20-second period were computed using FFT (Fast Fourier Transformation), and the ratio of low frequency power (0.05-0.15 Hz) to high frequency power (0.15-0.4 Hz) (L/H) of PSA were analyzed as an index of sympathetic activity. The PSA was examined by the following three parameters; L/H at rest during the 80-second period from 20 to 100 seconds (static function), the L/H variation between each 20-second period from 0 to 160 seconds (variation) and the ratio of L/H to that in the upright position (dynamic change). The results of PSA were compared with those of pulse wave velocity (PWV) and the coefficient of variation of the RR interval (CVRR), and association between attacks of vertigo and ANF was determined. The results of static function of PSA and the results of PWV and CVRR were very similar, indicating that both methods are useful for evaluating ANF in vertiginous patients. In the AND group the variation in sympathetic activity tended to be larger in patients with sympathetic hyperfunction and parasympathetic hypofunction and in the patients with sympathetic hypofunction and parasympathetic hyperfunction resulting from PWV and CVRR, than in the controls. The dynamic change in patients with sympathetic hyperfunction and parasympathetic hypofunction resulting from PWV and CVRR was also significantly lower than that in the controls (p < 0.01). Some patients in the AND group already showed excessive sympathetic hyperfunction at rest, and changing the position from supine to upright might trigger sympathetic hypofunction, causing an attack of vertigo. The PSA results in the VBI group were similar to those in the controls, suggesting that sympathetic dysfunction did not affect VBI induced vertigo.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schwaiger, M.; Hutchins, G.D.; Kalff, V.

Positron emission tomography in combination with the newly introduced catecholamine analogue ({sup 11}C)hydroxyephedrine (({sup 11}C)HED) enables the noninvasive delineation of sympathetic nerve terminals of the heart. To address the ongoing controversy over possible reinnervation of the human transplant, 5 healthy control subjects and 11 patients were studied after cardiac transplant by this imaging approach. Regional ({sup 11}C)HED retention was compared to regional blood flow as assessed by rubidium-82. Transplant patients were divided into two groups. Group I had recent (less than 1 yr, 4.4 +/- 2.3 mo) surgery, while group II patients underwent cardiac transplantation more than 2 yr beforemore » imaging (3.5 +/- 1.3 yr). ({sup 11}C)HED retention paralleled blood flow in normals, but was homogeneously reduced in group I. In contrast, group II patients revealed heterogeneous ({sup 11}C)HED retention, with increased uptake in the proximal anterior and septal wall. Quantitative evaluation of ({sup 11}C)HED retention revealed a 70% reduction in group I and 59% reduction in group II patients (P less than 0.001). In group II patients, ({sup 11}C)HED retention reached 60% of normal in the proximal anterior wall. These data suggest the presence of neuronal tissue in the transplanted human heart, which may reflect regional sympathetic reinnervation.« less

Neurovascular control of blood pressure is influenced by aging, sex, and sex hormones.

PubMed

Baker, Sarah E; Limberg, Jacqueline K; Ranadive, Sushant M; Joyner, Michael J

2016-12-01

In this review, we highlight that the relationship between muscle sympathetic nerve activity (MSNA) and mean arterial pressure is complex, differs by sex, and changes with age. In young men there is an inverse relationship between MSNA and cardiac output where high MSNA is compensated for by low cardiac output. This inverse relationship is not seen in older men. In young women sympathetic vasoconstriction is offset by β-adrenoreceptor mediated vasodilation, limiting the ability of young women to maintain blood pressure in response to orthostatic stress. However, β-mediated dilation in women is attenuated with age, leading to unopposed α-adrenergic vasoconstriction and a rise in the direct transduction of MSNA into increases in blood pressure. We propose that these changes with age and menopausal status are major contributing factors in the increased prevalence of hypertension in older women. In addition to aging, we highlight that changes in sex hormones in young women (across the menstrual cycle, with oral contraceptive use, or with pregnancy) influence MSNA and the transduction of MSNA into increases in blood pressure. It is likely that the β-adrenergic receptors and/or changes in baroreflex sensitivity play a large role in these sex differences and changes with alterations in sex hormones. Copyright © 2016 the American Physiological Society.

Diverse autonomic regulation of pupillary function and the cardiovascular system during alcohol withdrawal.

PubMed

Jochum, Thomas; Hoyme, Johannes; Schulz, Steffen; Weißenfels, Markus; Voss, Andreas; Bär, Karl-Jürgen

2016-02-01

Previous research indicated the complexity of autonomic dysfunction during acute alcohol withdrawal. This study aimed to investigate the pupillary light reflex as an indicator of midbrain and brainstem regulatory systems in relation to cardiovascular autonomic function. Thirty male patients were included in the study. They were investigated during acute alcohol withdrawal syndrome and 24h later during clomethiazole treatment and compared to healthy controls. Parameters of pupillary light reflex of both eyes as well as heart rate variability, blood pressure variability and baroreflex sensitivity (BRS) were studied. We observed significantly reduced sympathetic (small diameter, e.g., left eye: 5.00 in patients vs. 5.91 mm in controls) and vagal modulation (e.g., prolonged latencies, left eye: 0.28 vs. 0.26 ms) regarding both pupils during acute alcohol withdrawal syndrome. Cardiovascular parameters showed reduced vagal modulation (e.g., b-slope of BRS: 7. 57 vs. 13.59 ms/mm Hg) and mixed results for sympathetic influence. After 24h, autonomic dysfunction improved significantly, both for the pupils (e.g., left diameter: 5.38 mm) and the heart (e.g., b-slope of BRS: 9.34 ms/mm Hg). While parameters obtained from the pupil correlated with cardiac autonomic function (e.g, BRS and left diameter: r=0.564) in healthy controls, no such pattern was observed in patients. Results obtained from the pupil during acute alcohol withdrawal do not simply mirror autonomic dysfunction regarding the heart. Pupillary and cardiovascular changes after 24h indicate state dependencies of the results. The findings are discussed with respect to autonomic mechanisms and potentially involved brain regions. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Quantifying Effects of Pharmacological Blockers of Cardiac Autonomous Control Using Variability Parameters.

PubMed

Miyabara, Renata; Berg, Karsten; Kraemer, Jan F; Baltatu, Ovidiu C; Wessel, Niels; Campos, Luciana A

2017-01-01

Objective: The aim of this study was to identify the most sensitive heart rate and blood pressure variability (HRV and BPV) parameters from a given set of well-known methods for the quantification of cardiovascular autonomic function after several autonomic blockades. Methods: Cardiovascular sympathetic and parasympathetic functions were studied in freely moving rats following peripheral muscarinic (methylatropine), β1-adrenergic (metoprolol), muscarinic + β1-adrenergic, α1-adrenergic (prazosin), and ganglionic (hexamethonium) blockades. Time domain, frequency domain and symbolic dynamics measures for each of HRV and BPV were classified through paired Wilcoxon test for all autonomic drugs separately. In order to select those variables that have a high relevance to, and stable influence on our target measurements (HRV, BPV) we used Fisher's Method to combine the p -value of multiple tests. Results: This analysis led to the following best set of cardiovascular variability parameters: The mean normal beat-to-beat-interval/value (HRV/BPV: meanNN), the coefficient of variation (cvNN = standard deviation over meanNN) and the root mean square differences of successive (RMSSD) of the time domain analysis. In frequency domain analysis the very-low-frequency (VLF) component was selected. From symbolic dynamics Shannon entropy of the word distribution (FWSHANNON) as well as POLVAR3, the non-linear parameter to detect intermittently decreased variability, showed the best ability to discriminate between the different autonomic blockades. Conclusion: Throughout a complex comparative analysis of HRV and BPV measures altered by a set of autonomic drugs, we identified the most sensitive set of informative cardiovascular variability indexes able to pick up the modifications imposed by the autonomic challenges. These indexes may help to increase our understanding of cardiovascular sympathetic and parasympathetic functions in translational studies of experimental diseases.

Exercise training starting at weaning age preserves cardiac pacemaker function in adulthood of diet-induced obese rats.

PubMed

Carvalho de Lima, Daniel; Guimarães, Juliana Bohnen; Rodovalho, Gisele Vieira; Silveira, Simonton Andrade; Haibara, Andrea Siqueira; Coimbra, Cândido Celso

2014-08-01

Peripheral sympathetic overdrive in young obese subjects contributes to further aggravation of insulin resistance, diabetes, and hypertension, thus inducing worsening clinical conditions in adulthood. Exercise training has been considered a strategy to repair obesity autonomic dysfunction, thereby reducing the cardiometabolic risk. Therefore, the aim of this study was to assess the effect of early exercise training, starting immediately after weaning, on cardiac autonomic control in diet-induced obese rats. Male Wistar rats (weaning) were divided into four groups: (i) a control group (n = 6); (ii) an exercise-trained control group (n = 6); (iii) a diet-induced obesity group (n = 6); and (iv) an exercise-trained diet-induced obesity group (n = 6). The development of obesity was induced by 9 weeks of palatable diet intake, and the training program was implemented in a motor-driven treadmill (5 times per week) during the same period. After this period, animals were submitted to vein and artery catheter implantation to assess cardiac autonomic balance by methylatropine (3 mg/kg) and propranolol (4 mg/kg) administration. Exercise training increased running performance in both groups (p < 0.05). Exercise training also prevented the increased resting heart rate in obese rats, which seemed to be related to cardiac pacemaker activity preservation (p < 0.05). Additionally, the training program preserved the pressure and bradycardia responses to autonomic blockade in obese rats (p < 0.05). An exercise program beginning at weaning age prevents cardiovascular dysfunction in obese rats, indicating that exercise training may be used as a nonpharmacological therapeutic strategy for the treatment of cardiometabolic diseases.

Pulse Wave Velocity Predicts Response to Renal Denervation in Isolated Systolic Hypertension.

PubMed

Fengler, Karl; Rommel, Karl-Philipp; Hoellriegel, Robert; Blazek, Stephan; Besler, Christian; Desch, Steffen; Schuler, Gerhard; Linke, Axel; Lurz, Philipp

2017-05-17

Renal sympathetic denervation seems to be less effective as a treatment for hypertension in patients with isolated systolic hypertension, a condition associated with elevated central arterial stiffness. Because isolated systolic hypertension can also be caused by wave reflection or increased cardiac output, a more differentiated approach might improve patient preselection for renal sympathetic denervation. We sought to evaluate the additional predictive value of invasive pulse wave velocity for response to renal sympathetic denervation in patients with combined versus isolated systolic hypertension. Patients scheduled for renal sympathetic denervation underwent additional invasive measurement of pulse wave velocity and pulse pressure before denervation. Blood pressure was assessed via ambulatory measurement at baseline and after 3 months. In total 109 patients (40 patients with isolated systolic hypertension) were included in our analysis. After 3 months, blood pressure reduction was more pronounced among patients with combined hypertension compared with patients with isolated systolic hypertension (systolic 24-hour average 9.3±10.5 versus 5.0±11.5 mm Hg, P =0.046). However, when stratifying patients with isolated systolic hypertension by invasive pulse wave velocity, patients in the lowest tertile of pulse wave velocity had comparable blood pressure reduction (12.1±12.6 mm Hg, P =0.006) despite lower baseline blood pressure than patients with combined hypertension (systolic 24-hour average 154.8±12.5 mm Hg in combined hypertension versus 141.2±8.1, 148.4±10.9, and 150.5±12.7 mm Hg, respectively, by tertiles of pulse wave velocity, P =0.002). Extended assessment of arterial stiffness can help improve patient preselection for renal sympathetic denervation and identify a subgroup of isolated systolic hypertension patients who benefit from sympathetic modulation. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Brain-Heart Interaction: Cardiac Complications After Stroke.

PubMed

Chen, Zhili; Venkat, Poornima; Seyfried, Don; Chopp, Michael; Yan, Tao; Chen, Jieli

2017-08-04

Neurocardiology is an emerging specialty that addresses the interaction between the brain and the heart, that is, the effects of cardiac injury on the brain and the effects of brain injury on the heart. This review article focuses on cardiac dysfunction in the setting of stroke such as ischemic stroke, brain hemorrhage, and subarachnoid hemorrhage. The majority of post-stroke deaths are attributed to neurological damage, and cardiovascular complications are the second leading cause of post-stroke mortality. Accumulating clinical and experimental evidence suggests a causal relationship between brain damage and heart dysfunction. Thus, it is important to determine whether cardiac dysfunction is triggered by stroke, is an unrelated complication, or is the underlying cause of stroke. Stroke-induced cardiac damage may lead to fatality or potentially lifelong cardiac problems (such as heart failure), or to mild and recoverable damage such as neurogenic stress cardiomyopathy and Takotsubo cardiomyopathy. The role of location and lateralization of brain lesions after stroke in brain-heart interaction; clinical biomarkers and manifestations of cardiac complications; and underlying mechanisms of brain-heart interaction after stroke, such as the hypothalamic-pituitary-adrenal axis; catecholamine surge; sympathetic and parasympathetic regulation; microvesicles; microRNAs; gut microbiome, immunoresponse, and systemic inflammation, are discussed. © 2017 American Heart Association, Inc.

Sympathetic Response and Outcomes Following Renal Denervation in Patients With Chronic Heart Failure: 12-Month Outcomes From the Symplicity HF Feasibility Study.

PubMed

Hopper, Ingrid; Gronda, Edoardo; Hoppe, Uta C; Rundqvist, Bengt; Marwick, Thomas H; Shetty, Sharad; Hayward, Christopher; Lambert, Thomas; Hering, Dagmara; Esler, Murray; Schlaich, Markus; Walton, Antony; Airoldi, Flavio; Brandt, Mathias C; Cohen, Sidney A; Reiters, Pascalle; Krum, Henry

2017-09-01

Heart failure (HF) is associated with chronic sympathetic activation. Renal denervation (RDN) aims to reduce sympathetic activity by ablating the renal sympathetic nerves. We investigated the effect of RDN in patients with chronic HF and concurrent renal dysfunction in a prospective, multicenter, single-arm feasibility study. Thirty-nine patients with chronic systolic HF (left ventricular ejection fraction [LVEF] <40%, New York Heart Association class II-III,) and renal impairment (estimated glomerular filtration rate [eGFR; assessed with the use of the Modification of Diet in Renal Disease equation] < 75 mL • min -1  • 1.73 m -2 ) on stable medical therapy were enrolled. Mean age was 65 ± 11 years; 62% had ischemic HF. The average number of ablations per patient was 13 ± 3. No protocol-defined safety events were associated with the procedure. One subject experienced a renal artery occlusion that was possibly related to the denervation procedure. Statistically significant reductions in N-terminal pro-B-type natriuretic peptide (NT-proBNP; 1530 ± 1228 vs 1428 ± 1844 ng/mL; P = .006) and 120-minute glucose tolerance test (11.2 ± 5.1 vs 9.9 ± 3.6; P = .026) were seen at 12 months, but there was no significant change in LVEF (28 ± 9% vs 29 ± 11%; P= .536), 6-minute walk test (384 ± 96 vs 391 ± 97 m; P= .584), or eGFR (52.6 ± 15.3 vs 52.3 ± 18.5 mL • min -1  • 1.73 m -2 ; P= .700). RDN was associated with reductions in NT-proBNP and 120-minute glucose tolerance test in HF patients 12 months after RDN treatment. There was no deterioration in other indices of cardiac and renal function in this small feasibility study. Copyright © 2017 Elsevier Inc. All rights reserved.

Muscle sympathetic nerve responses to passive and active one-legged cycling: insights into the contributions of central command.

PubMed

Doherty, Connor J; Incognito, Anthony V; Notay, Karambir; Burns, Matthew J; Slysz, Joshua T; Seed, Jeremy D; Nardone, Massimo; Burr, Jamie F; Millar, Philip J

2018-01-01

The contribution of central command to the peripheral vasoconstrictor response during exercise has been investigated using primarily handgrip exercise. The purpose of the present study was to compare muscle sympathetic nerve activity (MSNA) responses during passive (involuntary) and active (voluntary) zero-load cycling to gain insights into the effects of central command on sympathetic outflow during dynamic exercise. Hemodynamic measurements and contralateral leg MSNA (microneurography) data were collected in 18 young healthy participants at rest and during 2 min of passive and active zero-load one-legged cycling. Arterial baroreflex control of MSNA burst occurrence and burst area were calculated separately in the time domain. Blood pressure and stroke volume increased during exercise ( P < 0.0001) but were not different between passive and active cycling ( P > 0.05). In contrast, heart rate, cardiac output, and total vascular conductance were greater during the first and second minute of active cycling ( P < 0.001). MSNA burst frequency and incidence decreased during passive and active cycling ( P < 0.0001), but no differences were detected between exercise modes ( P > 0.05). Reductions in total MSNA were attenuated during the first ( P < 0.0001) and second ( P = 0.0004) minute of active compared with passive cycling, in concert with increased MSNA burst amplitude ( P = 0.02 and P = 0.005, respectively). The sensitivity of arterial baroreflex control of MSNA burst occurrence was lower during active than passive cycling ( P = 0.01), while control of MSNA burst strength was unchanged ( P > 0.05). These results suggest that central feedforward mechanisms are involved primarily in modulating the strength, but not the occurrence, of a sympathetic burst during low-intensity dynamic leg exercise. NEW & NOTEWORTHY Muscle sympathetic nerve activity burst frequency decreased equally during passive and active cycling, but reductions in total muscle sympathetic nerve activity were attenuated during active cycling. These results suggest that central command primarily regulates the strength, not the occurrence, of a muscle sympathetic burst during low-intensity dynamic leg exercise.

Renal neural mechanisms in salt-sensitive hypertension.

PubMed

DiBona, G F

1995-01-01

Genetic forms of salt (NaCl)-sensitive hypertension are characterized by increased renal sympathetic nerve activity responses to environmental stimuli. The increases in renal sympathetic nerve activity produce marked changes in renal function with renal vasoconstriction and sodium and water retention which can contribute to the initiation, development and maintenance of hypertension. In genetic forms of NaCl-sensitive hypertension, increased dietary NaCl intake produces alterations in norepinephrine kinetics with decreased concentrations of norepinephrine in regions of the anterior hypothalamus which are critical for the regulation of peripheral sympathetic nerve activity. This local central decrease in tonic alpha 2 adrenoceptor sympathoinhibitory input leads to increased peripheral (renal) sympathetic nerve activity and hypertension. Similarly, with increased dietary NaCl intake, patients with NaCl-sensitive hypertension develop increased arterial pressure, renal vasoconstriction, increased glomerular capillary pressure and increased urinary albumin excretion. Thus, increased dietary NaCl intake can, via central nervous system actions, produce increases in renal sympathetic nerve activity whose renal functional effects contribute to the pathophysiology of hypertension.

Pneumatic antishock garment inflation activates the human sympathetic nervous system by abdominal compression.

PubMed

Garvin, Nathan M; Levine, Benjamin D; Raven, Peter B; Pawelczyk, James A

2014-01-01

Pneumatic antishock garments (PASG) have been proposed to exert their blood pressure-raising effect mechanically, i.e. by increasing venous return and vascular resistance of the lower body. We tested whether, alternatively, PASG inflation activates the sympathetic nervous system. Five men and four women wore PASG while mean arterial pressure (MAP), muscle sympathetic nerve activity (MSNA), heart rate and stroke volume were measured. One leg bladder (LEG) and the abdominal bladder (ABD) of the trousers were inflated individually and in combination (ABD+LEG), at 60 or 90 mmHg for 3 min. By the end of 3 min of inflation, conditions that included the ABD region caused significant increases in MAP in a dose-dependent fashion (7 ± 2, 8 ± 3, 14 ± 4 and 13 ± 5 mmHg for ABD60, ABD+LEG60, ABD90 and ABD+LEG90, respectively, P < 0.05). Likewise, inflation that included ABD caused significant increases in total MSNA compared with control values [306 ± 70, 426 ± 98 and 247 ± 79 units for ABD60, ABD90 and ABD+LEG90, respectively, P < 0.05 (units = burst frequency × burst amplitude]. There were no changes in MAP or MSNA in the LEG-alone conditions. The ABD inflation also caused a significant decrease in stroke volume (-11 ± 3 and -10 ± 3 ml per beat in ABD90 and ABD+LEG90, respectively, P < 0.05) with no change in cardiac output. Neither cardiopulmonary receptor deactivation nor mechanical effects can account for a slowly developing rise in both sympathetic activity and blood pressure during ABD inflation. Rather, these data provide direct evidence that PASG inflation activates the sympathetic nervous system secondarily to abdominal, but not leg, compression.

Renal hemodynamic effects of activation of specific renal sympathetic nerve fiber groups.

PubMed

DiBona, G F; Sawin, L L

1999-02-01

To examine the effect of activation of a unique population of renal sympathetic nerve fibers on renal blood flow (RBF) dynamics, anesthetized rats were instrumented with a renal sympathetic nerve activity (RSNA) recording electrode and an electromagnetic flow probe on the ipsilateral renal artery. Peripheral thermal receptor stimulation (external heat) was used to activate a unique population of renal sympathetic nerve fibers and to increase total RSNA. Total RSNA was reflexly increased to the same degree with somatic receptor stimulation (tail compression). Arterial pressure and heart rate were increased by both stimuli. Total RSNA was increased to the same degree by both stimuli but external heat produced a greater renal vasoconstrictor response than tail compression. Whereas both stimuli increased spectral density power of RSNA at both cardiac and respiratory frequencies, modulation of RBF variability by fluctuations of RSNA was small at these frequencies, with values for the normalized transfer gain being approximately 0.1 at >0.5 Hz. During tail compression coherent oscillations of RSNA and RBF were found at 0.3-0.4 Hz with normalized transfer gain of 0.33 +/- 0.02. During external heat coherent oscillations of RSNA and RBF were found at both 0.2 and 0.3-0.4 Hz with normalized transfer gains of 0. 63 +/- 0.05 at 0.2 Hz and 0.53 +/- 0.04 to 0.36 +/- 0.02 at 0.3-0.4 Hz. Renal denervation eliminated the oscillations in RBF at both 0.2 and 0.3-0.4 Hz. These findings indicate that despite similar increases in total RSNA, external heat results in a greater renal vasoconstrictor response than tail compression due to the activation of a unique population of renal sympathetic nerve fibers with different frequency-response characteristics of the renal vasculature.

The association of birth weight and infant growth with childhood autonomic nervous system activity and its mediating effects on energy-balance-related behaviours-the ABCD study.

PubMed

van Deutekom, Arend W; Chinapaw, Mai Jm; Gademan, Maaike Gj; Twisk, Jos Wr; Gemke, Reinoud Jbj; Vrijkotte, Tanja Gm

2016-08-01

The purpose of this study was to examine the association of birth weight and infant growth with childhood autonomic nervous system (ANS) activity and to assess whether ANS activity mediates the associations of birth weight and infant growth with energy-balance-related behaviours, including energy intake, satiety response, physical activity and screen time. In 2089 children, we prospectively collected birth weight, infant growth defined as conditional weight and height gain between birth and 12 months and-at 5 years-indices of cardiac ANS activity and parent-reported energy-balance-related behaviours. A mediation analysis was conducted, based on MacKinnon's multivariate extension of the product-of-coefficients strategy. Birth weight and infant height gain were inversely associated with sympathetic, but not parasympathetic, activity at age 5. Infant weight gain was not associated with childhood ANS activity. Infant weight gain was predictive of increased childhood screen time and infant height gain of diminished childhood energy intake, but sympathetic activity did not mediate these associations. Low-birth-weight children have higher sympathetic activity, which is considered a risk factor for cardiovascular disease. Height gain in infancy seems to be beneficial for childhood sympathetic activity. However, sympathetic activity was no mediator of the associations of infant growth with childhood energy-balance-related behaviours. As individual differences in ANS activity predict increased risk of cardiovascular disease, these differences may offer insight into the early-life origins of chronic diseases and provide further basis for public health strategies to optimize birth weight and infant growth. © The Author 2016; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.

Sleep electroencephalography and heart rate variability interdependence amongst healthy subjects and insomnia/schizophrenia patients.

PubMed

Chaparro-Vargas, Ramiro; Schilling, Claudia; Schredl, Michael; Cvetkovic, Dean

2016-01-01

The quantification of interdependencies within autonomic nervous system has gained increasing importance to characterise healthy and psychiatric disordered subjects. The present work introduces a biosignal processing approach, suggesting a computational resource to estimate coherent or synchronised interactions as an eventual supportive aid in the diagnosis of primary insomnia and schizophrenia pathologies. By deploying linear, nonlinear and statistical methods upon 25 electroencephalographic and electrocardiographic overnight sleep recordings, the assessment of cross-correlation, wavelet coherence and [Formula: see text]:[Formula: see text] phase synchronisation is focused on tracking discerning features amongst the clinical cohorts. Our results indicate that certain neuronal oscillations interact with cardiac power bands in distinctive ways responding to standardised sleep stages and patient groups, which promotes the hypothesis of subtle functional dynamics between neuronal assembles and (para)sympathetic activity subject to pathophysiological conditions.

Temperament affects sympathetic nervous function in a normal population.

PubMed

Kim, Bora; Lee, Jae-Hon; Kang, Eun-Ho; Yu, Bum-Hee

2012-09-01

Although specific temperaments have been known to be related to autonomic nervous function in some psychiatric disorders, there are few studies that have examined the relationship between temperaments and autonomic nervous function in a normal population. In this study, we examined the effect of temperament on the sympathetic nervous function in a normal population. Sixty eight healthy subjects participated in the present study. Temperament was assessed using the Korean version of the Cloninger Temperament and Character Inventory (TCI). Autonomic nervous function was determined by measuring skin temperature in a resting state, which was recorded for 5 minutes from the palmar surface of the left 5th digit using a thermistor secured with a Velcro® band. Pearson's correlation analysis and multiple linear regression were used to examine the relationship between temperament and skin temperature. A higher harm avoidance score was correlated with a lower skin temperature (i.e. an increased sympathetic tone; r=-0.343, p=0.004) whereas a higher persistence score was correlated with a higher skin temperature (r=0.433, p=0.001). Hierarchical linear regression analysis revealed that harm avoidance was able to predict the variance of skin temperature independently, with a variance of 7.1% after controlling for sex, blood pressure and state anxiety and persistence was the factor predicting the variance of skin temperature with a variance of 5.0%. These results suggest that high harm avoidance is related to an increased sympathetic nervous function whereas high persistence is related to decreased sympathetic nervous function in a normal population.

Temperament Affects Sympathetic Nervous Function in a Normal Population

PubMed Central

Kim, Bora; Lee, Jae-Hon; Kang, Eun-Ho

2012-01-01

Objective Although specific temperaments have been known to be related to autonomic nervous function in some psychiatric disorders, there are few studies that have examined the relationship between temperaments and autonomic nervous function in a normal population. In this study, we examined the effect of temperament on the sympathetic nervous function in a normal population. Methods Sixty eight healthy subjects participated in the present study. Temperament was assessed using the Korean version of the Cloninger Temperament and Character Inventory (TCI). Autonomic nervous function was determined by measuring skin temperature in a resting state, which was recorded for 5 minutes from the palmar surface of the left 5th digit using a thermistor secured with a Velcro® band. Pearson's correlation analysis and multiple linear regression were used to examine the relationship between temperament and skin temperature. Results A higher harm avoidance score was correlated with a lower skin temperature (i.e. an increased sympathetic tone; r=-0.343, p=0.004) whereas a higher persistence score was correlated with a higher skin temperature (r=0.433, p=0.001). Hierarchical linear regression analysis revealed that harm avoidance was able to predict the variance of skin temperature independently, with a variance of 7.1% after controlling for sex, blood pressure and state anxiety and persistence was the factor predicting the variance of skin temperature with a variance of 5.0%. Conclusion These results suggest that high harm avoidance is related to an increased sympathetic nervous function whereas high persistence is related to decreased sympathetic nervous function in a normal population. PMID:22993530

Sympathetic neural control of the kidney in hypertension.

PubMed

DiBona, G F

1992-01-01

Efferent renal sympathetic nerve activity is elevated in human essential hypertension as well as in several forms of experimental hypertension in animals. In addition, bilateral complete renal denervation delays the development and/or attenuates the magnitude of the hypertension in several different forms of experimental hypertension in animals. Efferent renal sympathetic nerve activity is known to have dose-dependent effects on renal blood flow, the glomerular filtration rate, renal tubular sodium and water reabsorption, and the renin secretion rate, which are capable of contributing, singly or in combination, to the development, maintenance, and exacerbation of the hypertensive state. Of the many factors known to influence the central nervous system integrative regulation of efferent renal sympathetic nerve activity, two environmental factors, a high dietary sodium intake and environmental stress, are capable of significant interaction. This resultant increase in efferent renal sympathetic nerve activity and subsequent renal functional alterations can participate in the hypertensive process. This is especially evident in the presence of an underlying genetic predisposition to the development of hypertension. Thus, interactions between environmental and genetic influences can produce alterations in the sympathetic neural control of renal function that play an important role in hypertension.

Cardiovascular consequences of bed rest: effect on maximal oxygen uptake

NASA Technical Reports Server (NTRS)

Convertino, V. A.

1997-01-01

Maximal oxygen uptake (VO2max) is reduced in healthy individuals confined to bed rest, suggesting it is independent of any disease state. The magnitude of reduction in VO2max is dependent on duration of bed rest and the initial level of aerobic fitness (VO2max), but it appears to be independent of age or gender. Bed rest induces an elevated maximal heart rate which, in turn, is associated with decreased cardiac vagal tone, increased sympathetic catecholamine secretion, and greater cardiac beta-receptor sensitivity. Despite the elevation in heart rate, VO2max is reduced primarily from decreased maximal stroke volume and cardiac output. An elevated ejection fraction during exercise following bed rest suggests that the lower stroke volume is not caused by ventricular dysfunction but is primarily the result of decreased venous return associated with lower circulating blood volume, reduced central venous pressure, and higher venous compliance in the lower extremities. VO2max, stroke volume, and cardiac output are further compromised by exercise in the upright posture. The contribution of hypovolemia to reduced cardiac output during exercise following bed rest is supported by the close relationship between the relative magnitude (% delta) and time course of change in blood volume and VO2max during bed rest, and also by the fact that retention of plasma volume is associated with maintenance of VO2max after bed rest. Arteriovenous oxygen difference during maximal exercise is not altered by bed rest, suggesting that peripheral mechanisms may not contribute significantly to the decreased VO2max. However reduction in baseline and maximal muscle blood flow, red blood cell volume, and capillarization in working muscles represent peripheral mechanisms that may contribute to limited oxygen delivery and, subsequently, lowered VO2max. Thus, alterations in cardiac and vascular functions induced by prolonged confinement to bed rest contribute to diminution of maximal oxygen uptake and reserve capacity to perform physical work.

Alterations in electrodermal activity and cardiac parasympathetic tone during hypnosis.

PubMed

Kekecs, Zoltán; Szekely, Anna; Varga, Katalin

2016-02-01

Exploring autonomic nervous system (ANS) changes during hypnosis is critical for understanding the nature and extent of the hypnotic phenomenon and for identifying the mechanisms underlying the effects of hypnosis in different medical conditions. To assess ANS changes during hypnosis, electrodermal activity and pulse rate variability (PRV) were measured in 121 young adults. Participants either received hypnotic induction (hypnosis condition) or listened to music (control condition), and both groups were exposed to test suggestions. Blocks of silence and experimental sound stimuli were presented at baseline, after induction, and after de-induction. Skin conductance level (SCL) and high frequency (HF) power of PRV measured at each phase were compared between groups. Hypnosis decreased SCL compared to the control condition; however, there were no group differences in HF power. Furthermore, hypnotic suggestibility did not moderate ANS changes in the hypnosis group. These findings indicate that hypnosis reduces tonic sympathetic nervous system activity, which might explain why hypnosis is effective in the treatment of disorders with strong sympathetic nervous system involvement, such as rheumatoid arthritis, hot flashes, hypertension, and chronic pain. Further studies with different control conditions are required to examine the specificity of the sympathetic effects of hypnosis. © 2015 Society for Psychophysiological Research.

Symptoms of anxiety and mood disturbance alter cardiac and peripheral autonomic control in patients with metabolic syndrome.

PubMed

Toschi-Dias, Edgar; Trombetta, Ivani C; da Silva, Valdo José Dias; Maki-Nunes, Cristiane; Alves, Maria Janieire N N; Angelo, Luciana F; Cepeda, Felipe X; Martinez, Daniel G; Negrão, Carlos Eduardo; Rondon, Maria Urbana P B

2013-03-01

Previous investigations show that metabolic syndrome (MetSyn) causes sympathetic hyperactivation. Symptoms of anxiety and mood disturbance (AMd) provoke sympatho-vagal imbalance. We hypothesized that AMd would alter even further the autonomic function in patients with MetSyn. Twenty-six never-treated patients with MetSyn (ATP-III) were allocated to two groups, according to the levels of anxiety and mood disturbance: (1) with AMd (MetSyn + AMd, n = 15), and (2) without AMd (MetSyn, n = 11). Ten healthy control subjects were also studied (C, n = 10). AMd was determined using quantitative questionnaires. Muscle sympathetic nerve activity (MSNA, microneurography), blood pressure (oscillometric beat-to-beat basis), and heart rate (ECG) were measured during a baseline 10-min period. Spectral analysis of RR interval and systolic arterial pressure were analyzed, and the power of low (LF) and high (HF) frequency bands were determined. Sympatho-vagal balance was obtained by LF/HF ratio. Spontaneous baroreflex sensitivity (BRS) was evaluated by calculation of α-index. MSNA was greater in patients with MetSyn + AMd compared with MetSyn and C. Patients with MetSyn + AMd showed higher LF and lower HF power compared with MetSyn and C. In addition, LF/HF balance was higher in MetSyn + AMd than in MetSyn and C groups. BRS was decreased in MetSyn + AMd compared with MetSyn and C groups. Anxiety and mood disturbance alter autonomic function in patients with MetSyn. This autonomic dysfunction may contribute to the increased cardiovascular risk observed in patients with mood alterations.

Prognostic value of cardiac sympathetic nerve activity evaluated by [123I]m-iodobenzylguanidine imaging in patients with ST-segment elevation myocardial infarction.

PubMed

Kasama, Shu; Toyama, Takuji; Sumino, Hiroyuki; Kumakura, Hisao; Takayama, Yoshiaki; Minami, Kazutomo; Ichikawa, Shuichi; Matsumoto, Naoya; Sato, Yuichi; Kurabayashi, Masahiko

2011-01-01

Many studies have shown that cardiac sympathetic nerve activity evaluated by [(123)I]m-iodobenzylguanidine ([(123)I]MIBG) scintigraphic study during a stable period is useful for determining the prognosis of patients with chronic heart failure. To examine whether results of this imaging method performed 3 weeks after the onset of ST-segment elevation myocardial infarction (STEMI) are a reliable prognostic marker for patients with STEMI. The study analysed findings for 213 consecutive patients with STEMI undergoing [(123)I]MIBG scintigraphy. The left ventricular (LV) end-diastolic and end-systolic volume and LV ejection fraction (EF) were determined by left ventriculography or echocardiography 3 weeks after the onset of STEMI. The delayed total defect score, heart-to-mediastinum ratio and washout rate (WR) were also determined from [(123)I]MIBG scintigraphy at the same time. Of the 213 patients, 46 experienced major adverse cardiac events (MACE) during the study. The median follow-up period was 982 days. Patients were divided into an event-free group (n = 167; 78.4%) and a MACE group (n = 46; 21.6%). The LV and [(123)I]MIBG scintigraphic parameters in the event-free group were better than those in the MACE group. Multivariate Cox regression analyses revealed that WR was a significant predictor of MACE along with oral nicorandil (ATP-sensitive potassium channel opener) treatment and undergoing percutaneous coronary intervention. On Kaplan-Meier analysis, the event-free rate of patients with a WR<40% was significantly higher than that in patients with a WR ≥ 40% (p<0.001). Even when confined to patients with LVEF>45%, WR was a predictor of MACE, pump failure death, cardiac death and progression of heart failure in patients with STEMI. WR evaluated by [(123)I]MIBG scintigraphy 3 weeks after the onset of STEMI is a significant predictor of MACE in patients with STEMI, independent of LVEF.

Higher exercise intensity delays postexercise recovery of impedance-derived cardiac sympathetic activity.

PubMed

Michael, Scott; Jay, Ollie; Graham, Kenneth S; Davis, Glen M

2017-08-01

Systolic time intervals (STIs) provide noninvasive insights into cardiac sympathetic neural activity (cSNA). As the effect of exercise intensity on postexercise STI recovery is unclear, this study investigated the STI recovery profile after different exercise intensities. Eleven healthy males cycled for 8 min at 3 separate intensities: LOW (40%-45%), MOD (75%-80%), and HIGH (90%-95%) of heart-rate (HR) reserve. Bio-impedance cardiography was used to assess STIs - primarily pre-ejection period (PEP; inversely correlated with cSNA), as well as left ventricular ejection time (LVET) and PEP:LVET - during 10 min seated recovery immediately postexercise. Heart-rate variability (HRV), i.e., natural-logarithm of root mean square of successive differences (Ln-RMSSD), was calculated as an index of cardiac parasympathetic neural activity (cPNA). Higher preceding exercise intensity elicited a slower recovery of HR and Ln-RMSSD (p < 0.001), and these measures did not return to baseline by 10 min following any intensity (p ≤ 0.009). Recovery of STIs was also slower following higher intensity exercise (p ≤ 0.002). By 30 s postexercise, higher preceding intensity resulted in a lower PEP (98 ± 14 ms, 75 ± 6 ms, 66 ± 5 ms for LOW, MOD, and HIGH, respectively, p < 0.001). PEP recovered to baseline (143 ± 11 ms) by 5 min following LOW (139 ± 13 ms, p = 0.590) and by 10 min following MOD (145 ± 17 ms, p = 0.602), but was still suppressed at 10 min following HIGH (123 ± 21 ms, p = 0.012). Higher preceding exercise intensity attenuated the recovery of indices for cSNA (from STIs) and cPNA (from HRV) in a graded dose-response fashion. While exercise intensity must be considered, acute recovery may be a valuable period during which to concurrently monitor these noninvasive indices, to identify potentially abnormal cardiac autonomic responses.

Neural control of the kidney: functionally specific renal sympathetic nerve fibers.

PubMed

DiBona, G F

2000-11-01

The sympathetic nervous system provides differentiated regulation of the functions of various organs. This differentiated regulation occurs via mechanisms that operate at multiple sites within the classic reflex arc: peripherally at the level of afferent input stimuli to various reflex pathways, centrally at the level of interconnections between various central neuron pools, and peripherally at the level of efferent fibers targeted to various effectors within the organ. In the kidney, increased renal sympathetic nerve activity regulates the functions of the intrarenal effectors: the tubules, the blood vessels, and the juxtaglomerular granular cells. This enables a physiologically appropriate coordination between the circulatory, filtration, reabsorptive, excretory, and renin secretory contributions to overall renal function. Anatomically, each of these effectors has a dual pattern of innervation consisting of a specific and selective innervation by unmyelinated slowly conducting C-type renal sympathetic nerve fibers in addition to an innervation that is shared among all the effectors. This arrangement permits the maximum flexibility in the coordination of physiologically appropriate responses of the tubules, the blood vessels, and the juxtaglomerular granular cells to a variety of homeostatic requirements.

Functionally specific renal sympathetic nerve fibers: role in cardiovascular regulation.

PubMed

DiBona, G F

2001-06-01

The sympathetic nervous system provides differentiated regulation of the functions of various organs. This differentiated regulation occurs through mechanisms that operate at multiple sites within the classic reflex arc: peripherally at the level of afferent input stimuli to various reflex pathways, centrally at the level of interconnections between various central neuron pools, and peripherally at the level of efferent fibers targeted to various effectors within the organ. In the kidney, increased renal sympathetic nerve activity regulates the functions of the intrarenal effectors: the tubules, the blood vessels, and the juxtaglomerular granular cells. This enables a physiologically appropriate coordination between the circulatory, filtration, reabsorptive, excretory, and renin secretory contributions to overall renal function. Anatomically, each of these effectors has a dual pattern of innervation consisting of a specific and selective innervation by unmyelinated slowly conducting C-type renal sympathetic nerve fibers and an innervation that is shared among all the effectors. This arrangement facilitates maximum flexibility in the coordination of the tubules, the blood vessels, and the juxtaglomerular granular cells so as to produce physiologically appropriate responses to a variety of homeostatic requirements.

Electric injury, Part II: Specific injuries.

PubMed

Fish, R M

2000-01-01

Electric injury can cause disruption of cardiac rhythm and breathing, burns, fractures, dislocations, rhabdomyolysis, eye and ear injury, oral and gastrointestinal injury, vascular damage, disseminated intravascular coagulation, peripheral and spinal cord injury, and Reflex Sympathetic Dystrophy. Secondary trauma from falls, fires, flying debris, and inhalation injury can complicate the clinical picture. Diagnostic and treatment considerations for electric injuries are described in this article, which is the second part of a three-part series on electric injuries.

Altered Connexin 43 and Connexin 45 protein expression in the heart as a function of social and environmental stress in the prairie vole.

PubMed

Grippo, Angela J; Moffitt, Julia A; Henry, Matthew K; Firkins, Rachel; Senkler, Jonathan; McNeal, Neal; Wardwell, Joshua; Scotti, Melissa-Ann L; Dotson, Ashley; Schultz, Rachel

2015-01-01

Exposure to social and environmental stressors may influence behavior as well as autonomic and cardiovascular regulation, potentially leading to depressive disorders and cardiac dysfunction including elevated sympathetic drive, reduced parasympathetic function, and ventricular arrhythmias. The cellular mechanisms that underlie these interactions are not well understood. One mechanism may involve alterations in the expression of Connexin43 (Cx43) and Connexin45 (Cx45), gap junction proteins in the heart that play an important role in ensuring efficient cell-to-cell coupling and the maintenance of cardiac rhythmicity. The present study investigated the hypothesis that long-term social isolation, combined with mild environmental stressors, would produce both depressive behaviors and altered Cx43 and Cx45 expression in the left ventricle of prairie voles - a socially monogamous rodent model. Adult, female prairie voles were exposed to either social isolation (n = 22) or control (paired, n = 23) conditions (4 weeks), alone or in combination with chronic mild stress (CMS) (1 week). Social isolation, versus paired control conditions, produced significantly (p < 0.05) increased depressive behaviors in a 5-min forced swim test, and CMS exacerbated (p < 0.05) these behaviors. Social isolation (alone) reduced (p < 0.05) total Cx43 expression in the left ventricle; whereas CMS (but not isolation) increased (p < 0.05) total Cx45 expression and reduced (p < 0.05) the Cx43/Cx45 ratio, measured via Western blot analysis. The present findings provide insight into potential cellular mechanisms underlying altered cardiac rhythmicity associated with social and environmental stress in the prairie vole.

Nonlinearities of heart rate variability in animal models of impaired cardiac control: contribution of different time scales.

PubMed

Silva, Luiz Eduardo Virgilio; Lataro, Renata Maria; Castania, Jaci Airton; Silva, Carlos Alberto Aguiar; Salgado, Helio Cesar; Fazan, Rubens; Porta, Alberto

2017-08-01

Heart rate variability (HRV) has been extensively explored by traditional linear approaches (e.g., spectral analysis); however, several studies have pointed to the presence of nonlinear features in HRV, suggesting that linear tools might fail to account for the complexity of the HRV dynamics. Even though the prevalent notion is that HRV is nonlinear, the actual presence of nonlinear features is rarely verified. In this study, the presence of nonlinear dynamics was checked as a function of time scales in three experimental models of rats with different impairment of the cardiac control: namely, rats with heart failure (HF), spontaneously hypertensive rats (SHRs), and sinoaortic denervated (SAD) rats. Multiscale entropy (MSE) and refined MSE (RMSE) were chosen as the discriminating statistic for the surrogate test utilized to detect nonlinearity. Nonlinear dynamics is less present in HF animals at both short and long time scales compared with controls. A similar finding was found in SHR only at short time scales. SAD increased the presence of nonlinear dynamics exclusively at short time scales. Those findings suggest that a working baroreflex contributes to linearize HRV and to reduce the likelihood to observe nonlinear components of the cardiac control at short time scales. In addition, an increased sympathetic modulation seems to be a source of nonlinear dynamics at long time scales. Testing nonlinear dynamics as a function of the time scales can provide a characterization of the cardiac control complementary to more traditional markers in time, frequency, and information domains. NEW & NOTEWORTHY Although heart rate variability (HRV) dynamics is widely assumed to be nonlinear, nonlinearity tests are rarely used to check this hypothesis. By adopting multiscale entropy (MSE) and refined MSE (RMSE) as the discriminating statistic for the nonlinearity test, we show that nonlinear dynamics varies with time scale and the type of cardiac dysfunction. Moreover, as complexity metrics and nonlinearities provide complementary information, we strongly recommend using the test for nonlinearity as an additional index to characterize HRV. Copyright © 2017 the American Physiological Society.

Local renin-angiotensin system contributes to hyperthyroidism-induced cardiac hypertrophy.

PubMed

Kobori, H; Ichihara, A; Miyashita, Y; Hayashi, M; Saruta, T

1999-01-01

We have reported previously that thyroid hormone activates the circulating and tissue renin-angiotensin systems without involving the sympathetic nervous system, which contributes to cardiac hypertrophy in hyperthyroidism. This study examined whether the circulating or tissue renin-angiotensin system plays the principal role in hyperthyroidism-induced cardiac hypertrophy. The circulating renin-angiotensin system in Sprague-Dawley rats was fixed by chronic angiotensin II infusion (40 ng/min, 28 days) via mini-osmotic pumps. Daily i.p. injection of thyroxine (0.1 mg/kg per day, 28 days) was used to mimic hyperthyroidism. Serum free tri-iodothyronine, plasma renin activity, plasma angiotensin II, cardiac renin and cardiac angiotensin II were measured with RIAs. The cardiac expression of renin mRNA was evaluated by semiquantitative reverse transcriptase-polymerase chain reaction. Plasma renin activity and plasma angiotensin II were kept constant in the angiotensin II and angiotensin II+thyroxine groups (0.12+/-0.03 and 0.15+/-0.03 microgram/h per liter, 126+/-5 and 130+/-5 ng/l respectively) (means+/-s.e.m.). Despite stabilization of the circulating renin-angiotensin system, thyroid hormone induced cardiac hypertrophy (5.0+/-0.5 vs 3.5+/-0.1 mg/g) in conjunction with the increases in cardiac expression of renin mRNA, cardiac renin and cardiac angiotensin II (74+/-2 vs 48+/-2%, 6.5+/-0.8 vs 3.8+/-0.4 ng/h per g, 231+/-30 vs 149+/-2 pg/g respectively). These results indicate that the local renin-angiotensin system plays the primary role in the development of hyperthyroidism-induced cardiac hypertrophy.

Morphology of subcortical brain nuclei is associated with autonomic function in healthy humans.

PubMed

Ruffle, James K; Coen, Steven J; Giampietro, Vincent; Williams, Steven C R; Apkarian, A Vania; Farmer, Adam D; Aziz, Qasim

2018-01-01

The autonomic nervous system (ANS) is a brain body interface which serves to maintain homeostasis by influencing a plethora of physiological processes, including metabolism, cardiorespiratory regulation and nociception. Accumulating evidence suggests that ANS function is disturbed in numerous prevalent clinical disorders, including irritable bowel syndrome and fibromyalgia. While the brain is a central hub for regulating autonomic function, the association between resting autonomic activity and subcortical morphology has not been comprehensively studied and thus was our aim. In 27 healthy subjects [14 male and 13 female; mean age 30 years (range 22-53 years)], we quantified resting ANS function using validated indices of cardiac sympathetic index (CSI) and parasympathetic cardiac vagal tone (CVT). High resolution structural magnetic resonance imaging scans were acquired, and differences in subcortical nuclei shape, that is, 'deformation', contingent on resting ANS activity were investigated. CSI positively correlated with outward deformation of the brainstem, right nucleus accumbens, right amygdala and bilateral pallidum (all thresholded to corrected P < 0.05). In contrast, parasympathetic CVT negatively correlated with inward deformation of the right amygdala and pallidum (all thresholded to corrected P < 0.05). Left and right putamen volume positively correlated with CVT (r = 0.62, P = 0.0047 and r = 0.59, P = 0.008, respectively), as did the brainstem (r = 0.46, P = 0.049). These data provide novel evidence that resting autonomic state is associated with differences in the shape and volume of subcortical nuclei. Thus, subcortical morphological brain differences in various disorders may partly be attributable to perturbation in autonomic function. Further work is warranted to investigate these findings in clinical populations. Hum Brain Mapp 39:381-392, 2018. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

A Review of Neurogenic Stunned Myocardium

PubMed Central

Wongrakpanich, Supakanya; Agrawal, Akanksha; Yadlapati, Sujani; Kishlyansky, Marina; Figueredo, Vincent

2017-01-01

Neurologic stunned myocardium (NSM) is a phenomenon where neurologic events give rise to cardiac abnormalities. Neurologic events like stroke and seizures cause sympathetic storm and autonomic dysregulation that result in myocardial injury. The clinical presentation can involve troponin elevation, left ventricular dysfunction, and ECG changes. These findings are similar to Takotsubo cardiomyopathy and acute coronary syndrome. It is difficult to distinguish NSM from acute coronary syndrome based on clinical presentation alone. Because of this difficulty, a patient with NSM who is at high risk for coronary heart disease may undergo cardiac catheterization to rule out coronary artery disease. The objective of this review of literature is to enhance physician's awareness of NSM and its features to help tailor management according to the patient's clinical profile. PMID:28875040

Binge Ethanol and MDMA Combination Exacerbates Toxic Cardiac Effects by Inducing Cellular Stress

PubMed Central

Navarro-Zaragoza, Javier; Ros-Simó, Clara; Milanés, María-Victoria; Valverde, Olga; Laorden, María-Luisa

2015-01-01

Binge drinking is a common pattern of ethanol consumption among young people. Binge drinkers are especially susceptible to brain damage when other substances are co-administered, in particular 3,4 methylendioxymethamphetamine (MDMA). The aim of the present work was to study the mechanisms implicated in the adaptive changes observed after administration of these drugs of abuse. So, we have evaluated the cardiac sympathetic activity and the expression and activation of heat shock protein 27 (HSP27), after voluntary binge ethanol consumption, alone and in combination with MDMA. Both parameters are markers of stressful situations and they could be modified inducing several alterations in different systems. Adolescent mice received MDMA, ethanol or both (ethanol plus MDMA). Drinking in the dark (DID) procedure was used as a model of binge. Noradrenaline (NA) turnover, tyrosine hydroxylase (TH), TH phosphorylated at serine 31 and HSP27 expression and its phosphorylation at serine 82 were evaluated in adolescent mice 48 h, 72 h, and 7 days after treatments in the left ventricle. NA and normetanephrine (NMN) were determined by high-performance liquid chromatography (HPLC); TH and HSP27 expression and phosphorylation were measured by quantitative blot immunollabeling using specific antibodies. Ethanol and MDMA co-administration increased NA turnover and TH expression and phosphorylation versus the consumption of each one of these drugs. In parallel with the described modifications in the cardiac sympathetic activity, our results showed that binge ethanol+MDMA exposure is associated with an increase in HSP27 expression and phosphorylation in the left ventricle, supporting the idea that the combination of both drugs exacerbates the cellular stress induced by ethanol or MDMA alone. PMID:26509576

Modulation of cardiac autonomic tone in non-hypotensive hypovolemia during blood donation.

PubMed

Yadav, Kavita; Singh, Akanksha; Jaryal, Ashok Kumar; Coshic, Poonam; Chatterjee, Kabita; Deepak, K K

2017-08-01

Non-hypotensive hypovolemia, observed during mild haemorrhage or blood donation leads to reflex readjustment of the cardiac autonomic tone. In the present study, the cardiac autonomic tone was quantified using heart rate and blood pressure variability during and after non-hypotensive hypovolemia of blood donation. 86 voluntary healthy male blood donors were recruited for the study (age 35 ± 9 years; weight 78 ± 12 kg; height 174 ± 6 cms). Continuous lead II ECG and beat-to-beat blood pressure was recorded before, during and after blood donation followed by offline time and frequency domain analysis of HRV and BPV. The overall heart rate variability (SDNN and total power) did not change during or after blood donation. However, there was a decrease in indices that represent the parasympathetic component (pNN50 %, SDSD and HF) while an increase was observed in sympathetic component (LF) along with an increase in sympathovagal balance (LF:HF ratio) during blood donation. These changes were sustained for the period immediately following blood donation. No fall of blood pressure was observed during the period of study. The blood pressure variability showed an increase in the SDNN, CoV and RMSSD time domain measures in the post donation period. These results suggest that mild hypovolemia produced by blood donation is non-hypotensive but is associated with significant changes in the autonomic tone. The increased blood pressure variability and heart rate changes that are seen only in the later part of donation period could be because of the progressive hypovolemia associated parasympathetic withdrawal and sympathetic activation that manifest during the course of blood donation.

Central command does not suppress baroreflex control of cardiac sympathetic nerve activity at the onset of spontaneous motor activity in the decerebrate cat.

PubMed

Matsukawa, Kanji; Ishii, Kei; Asahara, Ryota; Idesako, Mitsuhiro

2016-10-01

Our laboratory has reported that central command blunts the sensitivity of the aortic baroreceptor-heart rate (HR) reflex at the onset of voluntary static exercise in animals. We have examined whether baroreflex control of cardiac sympathetic nerve activity (CSNA) and/or cardiovagal baroreflex sensitivity are altered at the onset of spontaneously occurring motor behavior, which was monitored with tibial nerve activity in paralyzed, decerebrate cats. CSNA exhibited a peak increase (126 ± 17%) immediately after exercise onset, followed by increases in HR and mean arterial pressure (MAP). With development of the pressor response, CSNA and HR decreased near baseline, although spontaneous motor activity was not terminated. Atropine methyl nitrate (0.1-0.2 mg/kg iv) with little central influence delayed the initial increase in HR but did not alter the response magnitudes of HR and CSNA, while atropine augmented the pressor response. The baroreflex-induced decreases in CSNA and HR elicited by brief occlusion of the abdominal aorta were challenged at the onset of spontaneous motor activity. Spontaneous motor activity blunted the baroreflex reduction in HR by aortic occlusion but did not alter the baroreflex inhibition of CSNA. Similarly, atropine abolished the baroreflex reduction in HR but did not influence the baroreflex inhibition of CSNA. Thus it is likely that central command increases CSNA and decreases cardiac vagal outflow at the onset of spontaneous motor activity while preserving baroreflex control of CSNA. Accordingly, central command must attenuate cardiovagal baroreflex sensitivity against an excess rise in MAP as estimated from the effect of muscarinic blockade. Copyright © 2016 the American Physiological Society.

Physical training associated with Enalapril but not to Losartan, results in better cardiovascular autonomic effects.

PubMed

Maida, Karina Delgado; Gastaldi, Ada Clarice; de Paula Facioli, Tabata; de Araújo, João Eduardo; de Souza, Hugo Celso Dutra

2017-03-01

We investigated the cardiovascular autonomic effects of physical training associated with Enalapril or Losartan pharmacological treatments in spontaneously hypertensive rats (SHR). SHRs, 18weeks of age (N=48) was assigned to either sedentary (N=24) and trained (N=24; aerobic training by swimming for 10wk). Each group was subdivided in 3 subgroups (N=8) vehicle (control); Enalapril (10mg·kg -1 ·d -1 ); and Losartan (5mg·kg -1 ·d -1 ). All animals received a 10-week treatment in drinking water. In the last week of the treatments, the animals had their femoral artery and vein cannulated for blood pressure recording and drug injection, respectively. The autonomic assessment was performed by means of different approaches: double cardiac autonomic block with atropine and propranolol, spectral analysis of heart rate variability (HRV) and systolic arterial pressure (SAPV) and assessment of baroreflex sensitivity (BRS). The groups treated with Enalapril, sedentary and trained, showed more significant decrease in blood pressure when compared to the other groups. Autonomic evaluation showed that the sedentary group treated with Enalapril or Losartan had similar results, characterized by decreased effect of sympathetic tone and/or increased effect of cardiac vagal tone associated with improved BRS. Isolated physical training attenuated only the effect of sympathetic tone. The association of physical training with Enalapril showed the best results, characterized by the predominance of vagal tone in cardiac autonomic balance, increased HRV, reduced SAPV and increased BRS. Enalapril and Losartan promoted similar beneficial cardiovascular autonomic effects in sedentary animals, while only the association of physical training with Enalapril potentiated these effects. Copyright © 2017 Elsevier B.V. All rights reserved.

Symbolic dynamics of heart rate variability - a promising tool to investigate cardiac sympathovagal control in attention deficit/hyperactivity disorder (ADHD)?

PubMed

Tonhajzerova, Ingrid; Farsky, Ivan; Mestanik, Michal; Visnovcova, Zuzana; Mestanikova, Andrea; Hrtanek, Igor; Ondrejka, Igor

2016-06-01

We aimed to evaluate complex cardiac sympathovagal control in attention deficit/hyperactivity disorder (ADHD) by using heart rate variability (HRV) nonlinear analysis - symbolic dynamics. We examined 29 boys with untreated ADHD and 25 healthy boys (age 8-13 years). ADHD symptoms were evaluated by ADHD-RS-IV scale. ECG was recorded in 3 positions: baseline supine position, orthostasis, and clinostasis. Symbolic dynamics indices were used for the assessment of complex cardiac sympathovagal regulation: normalised complexity index (NCI), normalised unpredictability index (NUPI), and pattern classification measures (0V%, 1V%, 2LV%, 2UV%). The results showed that HRV complexity was significantly reduced at rest (NUPI) and during standing position (NCI, NUPI) in ADHD group compared to controls. Cardiac-linked sympathetic index 0V% was significantly higher during all posture positions and cardiovagal index 2LV% was significantly lower to standing in boys suffering from ADHD. Importantly, ADHD symptom inattention positively correlated with 0V%, and negatively correlated with NCI, NUPI. Concluding, symbolic dynamics revealed impaired complex neurocardiac control characterised by potential cardiac beta-adrenergic overactivity and vagal deficiency at rest and to posture changes in boys suffering from ADHD that is correlated with inattention. We suggest that symbolic dynamics indices could represent promising cardiac biomarkers in ADHD.

Cardiac vagal flexibility and accurate personality impressions: Examining a physiological correlate of the good judge.

PubMed

Human, Lauren J; Mendes, Wendy Berry

2018-02-23

Research has long sought to identify which individuals are best at accurately perceiving others' personalities or are good judges, yet consistent predictors of this ability have been difficult to find. In the current studies, we revisit this question by examining a novel physiological correlate of social sensitivity, cardiac vagal flexibility, which reflects dynamic modulation of cardiac vagal control. We examined whether greater cardiac vagal flexibility was associated with forming more accurate personality impressions, defined as viewing targets more in line with their distinctive self-reported profile of traits, in two studies, including a thin-slice video perceptions study (N = 109) and a dyadic interaction study (N = 175). Across studies, we found that individuals higher in vagal flexibility formed significantly more accurate first impressions of others' more observable personality traits (e.g., extraversion, creativity, warmth). These associations held while including a range of relevant covariates, including cardiac vagal tone, sympathetic activation, and gender. In sum, social sensitivity as indexed by cardiac vagal flexibility is linked to forming more accurate impressions of others' observable traits, shedding light on a characteristic that may help to identify the elusive good judge and providing insight into its neurobiological underpinnings. © 2018 Wiley Periodicals, Inc.

Netrin-1 controls sympathetic arterial innervation.

PubMed

Brunet, Isabelle; Gordon, Emma; Han, Jinah; Cristofaro, Brunella; Broqueres-You, Dong; Liu, Chun; Bouvrée, Karine; Zhang, Jiasheng; del Toro, Raquel; Mathivet, Thomas; Larrivée, Bruno; Jagu, Julia; Pibouin-Fragner, Laurence; Pardanaud, Luc; Machado, Maria J C; Kennedy, Timothy E; Zhuang, Zhen; Simons, Michael; Levy, Bernard I; Tessier-Lavigne, Marc; Grenz, Almut; Eltzschig, Holger; Eichmann, Anne

2014-07-01

Autonomic sympathetic nerves innervate peripheral resistance arteries, thereby regulating vascular tone and controlling blood supply to organs. Despite the fundamental importance of blood flow control, how sympathetic arterial innervation develops remains largely unknown. Here, we identified the axon guidance cue netrin-1 as an essential factor required for development of arterial innervation in mice. Netrin-1 was produced by arterial smooth muscle cells (SMCs) at the onset of innervation, and arterial innervation required the interaction of netrin-1 with its receptor, deleted in colorectal cancer (DCC), on sympathetic growth cones. Function-blocking approaches, including cell type-specific deletion of the genes encoding Ntn1 in SMCs and Dcc in sympathetic neurons, led to severe and selective reduction of sympathetic innervation and to defective vasoconstriction in resistance arteries. These findings indicate that netrin-1 and DCC are critical for the control of arterial innervation and blood flow regulation in peripheral organs.

Netrin-1 controls sympathetic arterial innervation

PubMed Central

Brunet, Isabelle; Gordon, Emma; Han, Jinah; Cristofaro, Brunella; Broqueres-You, Dong; Liu, Chun; Bouvrée, Karine; Zhang, Jiasheng; del Toro, Raquel; Mathivet, Thomas; Larrivée, Bruno; Jagu, Julia; Pibouin-Fragner, Laurence; Pardanaud, Luc; Machado, Maria J.C.; Kennedy, Timothy E.; Zhuang, Zhen; Simons, Michael; Levy, Bernard I.; Tessier-Lavigne, Marc; Grenz, Almut; Eltzschig, Holger; Eichmann, Anne

2014-01-01

Autonomic sympathetic nerves innervate peripheral resistance arteries, thereby regulating vascular tone and controlling blood supply to organs. Despite the fundamental importance of blood flow control, how sympathetic arterial innervation develops remains largely unknown. Here, we identified the axon guidance cue netrin-1 as an essential factor required for development of arterial innervation in mice. Netrin-1 was produced by arterial smooth muscle cells (SMCs) at the onset of innervation, and arterial innervation required the interaction of netrin-1 with its receptor, deleted in colorectal cancer (DCC), on sympathetic growth cones. Function-blocking approaches, including cell type–specific deletion of the genes encoding Ntn1 in SMCs and Dcc in sympathetic neurons, led to severe and selective reduction of sympathetic innervation and to defective vasoconstriction in resistance arteries. These findings indicate that netrin-1 and DCC are critical for the control of arterial innervation and blood flow regulation in peripheral organs. PMID:24937433

Leptin regulation of bone resorption by the sympathetic nervous system and CART.

PubMed

Elefteriou, Florent; Ahn, Jong Deok; Takeda, Shu; Starbuck, Michael; Yang, Xiangli; Liu, Xiuyun; Kondo, Hisataka; Richards, William G; Bannon, Tony W; Noda, Masaki; Clement, Karine; Vaisse, Christian; Karsenty, Gerard

2005-03-24

Bone remodelling, the mechanism by which vertebrates regulate bone mass, comprises two phases, namely resorption by osteoclasts and formation by osteoblasts; osteoblasts are multifunctional cells also controlling osteoclast differentiation. Sympathetic signalling via beta2-adrenergic receptors (Adrb2) present on osteoblasts controls bone formation downstream of leptin. Here we show, by analysing Adrb2-deficient mice, that the sympathetic nervous system favours bone resorption by increasing expression in osteoblast progenitor cells of the osteoclast differentiation factor Rankl. This sympathetic function requires phosphorylation (by protein kinase A) of ATF4, a cell-specific CREB-related transcription factor essential for osteoblast differentiation and function. That bone resorption cannot increase in gonadectomized Adrb2-deficient mice highlights the biological importance of this regulation, but also contrasts sharply with the increase in bone resorption characterizing another hypogonadic mouse with low sympathetic tone, the ob/ob mouse. This discrepancy is explained, in part, by the fact that CART ('cocaine amphetamine regulated transcript'), a neuropeptide whose expression is controlled by leptin and nearly abolished in ob/ob mice, inhibits bone resorption by modulating Rankl expression. Our study establishes that leptin-regulated neural pathways control both aspects of bone remodelling, and demonstrates that integrity of sympathetic signalling is necessary for the increase in bone resorption caused by gonadal failure.

Sympatho-renal axis in chronic disease.

PubMed

Sobotka, Paul A; Mahfoud, Felix; Schlaich, Markus P; Hoppe, Uta C; Böhm, Michael; Krum, Henry

2011-12-01

Essential hypertension, insulin resistance, heart failure, congestion, diuretic resistance, and functional renal disease are all characterized by excessive central sympathetic drive. The contribution of the kidney's somatic afferent nerves, as an underlying cause of elevated central sympathetic drive, and the consequences of excessive efferent sympathetic signals to the kidney itself, as well as other organs, identify the renal sympathetic nerves as a uniquely logical therapeutic target for diseases linked by excessive central sympathetic drive. Clinical studies of renal denervation in patients with resistant hypertension using an endovascular radiofrequency ablation methodology have exposed the sympathetic link between these conditions. Renal denervation could be expected to simultaneously affect blood pressure, insulin resistance, sleep disorders, congestion in heart failure, cardiorenal syndrome and diuretic resistance. The striking epidemiologic evidence for coexistence of these disorders suggests common causal pathways. Chronic activation of the sympathetic nervous system has been associated with components of the metabolic syndrome, such as blood pressure elevation, obesity, dyslipidemia, and impaired fasting glucose with hyperinsulinemia. Over 50% of patients with essential hypertension are hyperinsulinemic, regardless of whether they are untreated or in a stable program of treatment. Insulin resistance is related to sympathetic drive via a bidirectional mechanism. In this manuscript, we review the data that suggests that selective impairment of renal somatic afferent and sympathetic efferent nerves in patients with resistant hypertension both reduces markers of central sympathetic drive and favorably impacts diseases linked through central sympathetics-insulin resistance, heart failure, congestion, diuretic resistance, and cardiorenal disorders.

Hibernating myocardium results in partial sympathetic denervation and nerve sprouting.

PubMed

Fernandez, Stanley F; Ovchinnikov, Vladislav; Canty, John M; Fallavollita, James A

2013-01-15

Hibernating myocardium due to chronic repetitive ischemia is associated with regional sympathetic nerve dysfunction and spontaneous arrhythmic death in the absence of infarction. Although inhomogeneity in regional sympathetic innervation is an acknowledged substrate for sudden death, the mechanism(s) responsible for these abnormalities in viable, dysfunctional myocardium (i.e., neural stunning vs. sympathetic denervation) and their association with nerve sprouting are unknown. Accordingly, markers of sympathetic nerve function and nerve sprouting were assessed in subendocardial tissue collected from chronically instrumented pigs with hibernating myocardium (n = 18) as well as sham-instrumented controls (n = 7). Hibernating myocardium exhibited evidence of partial sympathetic denervation compared with the normally perfused region and sham controls, with corresponding regional reductions in tyrosine hydroxylase protein (-32%, P < 0.001), norepinephrine uptake transport protein (-25%, P = 0.01), and tissue norepinephrine content (-45%, P < 0.001). Partial denervation induced nerve sprouting with regional increases in nerve growth factor precursor protein (31%, P = 0.01) and growth associated protein-43 (38%, P < 0.05). All of the changes in sympathetic nerve markers were similar in animals that developed sudden death (n = 9) compared with electively terminated pigs with hibernating myocardium (n = 9). In conclusion, sympathetic nerve dysfunction in hibernating myocardium is most consistent with partial sympathetic denervation and is associated with regional nerve sprouting. The extent of sympathetic remodeling is similar in animals that develop sudden death compared with survivors; this suggests that sympathetic remodeling in hibernating myocardium is not an independent trigger for sudden death. Nevertheless, sympathetic remodeling likely contributes to electrical instability in combination with other factors.

Hibernating myocardium results in partial sympathetic denervation and nerve sprouting

PubMed Central

Fernandez, Stanley F.; Ovchinnikov, Vladislav; Canty, John M.

2013-01-01

Hibernating myocardium due to chronic repetitive ischemia is associated with regional sympathetic nerve dysfunction and spontaneous arrhythmic death in the absence of infarction. Although inhomogeneity in regional sympathetic innervation is an acknowledged substrate for sudden death, the mechanism(s) responsible for these abnormalities in viable, dysfunctional myocardium (i.e., neural stunning vs. sympathetic denervation) and their association with nerve sprouting are unknown. Accordingly, markers of sympathetic nerve function and nerve sprouting were assessed in subendocardial tissue collected from chronically instrumented pigs with hibernating myocardium (n = 18) as well as sham-instrumented controls (n = 7). Hibernating myocardium exhibited evidence of partial sympathetic denervation compared with the normally perfused region and sham controls, with corresponding regional reductions in tyrosine hydroxylase protein (−32%, P < 0.001), norepinephrine uptake transport protein (−25%, P = 0.01), and tissue norepinephrine content (−45%, P < 0.001). Partial denervation induced nerve sprouting with regional increases in nerve growth factor precursor protein (31%, P = 0.01) and growth associated protein-43 (38%, P < 0.05). All of the changes in sympathetic nerve markers were similar in animals that developed sudden death (n = 9) compared with electively terminated pigs with hibernating myocardium (n = 9). In conclusion, sympathetic nerve dysfunction in hibernating myocardium is most consistent with partial sympathetic denervation and is associated with regional nerve sprouting. The extent of sympathetic remodeling is similar in animals that develop sudden death compared with survivors; this suggests that sympathetic remodeling in hibernating myocardium is not an independent trigger for sudden death. Nevertheless, sympathetic remodeling likely contributes to electrical instability in combination with other factors. PMID:23125211

Developmental changes in expression of GABAA receptor-channels in rat intrinsic cardiac ganglion neurones

PubMed Central

Fischer, Harald; Harper, Alexander A; Anderson, Colin R; Adams, David J

2005-01-01

The effects of γ-aminobutyric acid (GABA) on the electrophysiological properties of intracardiac neurones were investigated in the intracardiac ganglion plexus in situ and in dissociated neurones from neonatal, juvenile and adult rat hearts. Focal application of GABA evoked a depolarizing, excitatory response in both intact and dissociated intracardiac ganglion neurones. Under voltage clamp, both GABA and muscimol elicited inward currents at −60 mV in a concentration-dependent manner. The fast, desensitizing currents were mimicked by the GABAA receptor agonists muscimol and taurine, and inhibited by the GABAA receptor antagonists, bicuculline and picrotoxin. The GABAA0 antagonist (1,2,5,6-tetrahydropyridin-4-yl)methyl phosphonic acid (TPMPA), had no effect on GABA-induced currents, suggesting that GABAA receptor-channels mediate the response. The GABA-evoked current amplitude recorded from dissociated neurones was age dependent whereby the peak current density measured at −100 mV was ∼ 20 times higher for intracardiac neurones obtained from neonatal rats (P2–5) compared with adult rats (P45–49). The decrease in GABA sensitivity occurred during the first two postnatal weeks and coincides with maturation of the sympathetic innervation of the rat heart. Immunohistochemical staining using antibodies against GABA demonstrate the presence of GABA in the intracardiac ganglion plexus of the neonatal rat heart. Taken together, these results suggest that GABA and taurine may act as modulators of neurotransmission and cardiac function in the developing mammalian intrinsic cardiac nervous system. PMID:15731187

Strength Training Does Not Affect Vagal-cardiac Control or Cardiovagal Baroreflex Sensitivity in Young Healthy Subjects

DTIC Science & Technology

2005-03-01

shown to help control or lower arterial blood pressure (Carter JR et al. 2003; Kelley and Kelley 2000), and has been recommended as therapy for...as determined by a physician during a routine physical examination. The experimental protocol was approved by the Human Research Committee of Michigan...car diovagal and sympathetic responses to Valsalva’s maneuver. Med Sci Sports Exerc 34:928 935 Ekblom B, Kilbom ASA, Soltysiak J (1973) Physical

Effects of inspiratory impedance on the carotid-cardiac baroreflex response in humans.

DTIC Science & Technology

2004-08-01

seems con- traindicated, it is similar to the concurrent elevation in HR and arterial blood pressure responses observed dur- ing physical exercise.Two...expect withdrawal of vagal activity and no significant change in sympathetic activity with heart rate below 100 bpm during physical exercise [31]. To... quadriplegics . Am J Physiol Regulatory Integrative Comp Physiol 260: R576–R580 7. Convertino VA, Doerr DF, Eckberg DL, Fritsch JM, Vernikos-Danellis J

Polyvagal Theory and Developmental Psychopathology: Emotion Dysregulation and Conduct Problems from Preschool to Adolescence

PubMed Central

Beauchaine, Theodore P.; Gatzke-Kopp, Lisa; Mead, Hilary K.

2007-01-01

In science, theories lend coherence to vast amounts of descriptive information. However, current diagnostic approaches in psychopathology are primarily atheoretical, emphasizing description over etiological mechanisms. We describe the importance of Polyvagal Theory toward understanding the etiology of emotion dysregulation, a hallmark of psychopathology. When combined with theories of social reinforcement and motivation, Polyvagal Theory specifies etiological mechanisms through which distinct patterns of psychopathology emerge. In this paper, we summarize three studies evaluating autonomic nervous system functioning in children with conduct problems, ages 4-18. At all age ranges, these children exhibit attenuated sympathetic nervous system responses to reward, suggesting deficiencies in approach motivation. By middle school, this reward insensitivity is met with inadequate vagal modulation of cardiac output, suggesting additional deficiencies in emotion regulation. We propose a biosocial developmental model of conduct problems in which inherited impulsivity is amplified through social reinforcement of emotional lability. Implications for early intervention are discussed. PMID:17045726

Polyvagal Theory and developmental psychopathology: emotion dysregulation and conduct problems from preschool to adolescence.

PubMed

Beauchaine, Theodore P; Gatzke-Kopp, Lisa; Mead, Hilary K

2007-02-01

In science, theories lend coherence to vast amounts of descriptive information. However, current diagnostic approaches in psychopathology are primarily atheoretical, emphasizing description over etiological mechanisms. We describe the importance of Polyvagal Theory toward understanding the etiology of emotion dysregulation, a hallmark of psychopathology. When combined with theories of social reinforcement and motivation, Polyvagal Theory specifies etiological mechanisms through which distinct patterns of psychopathology emerge. In this paper, we summarize three studies evaluating autonomic nervous system functioning in children with conduct problems, ages 4-18. At all age ranges, these children exhibit attenuated sympathetic nervous system responses to reward, suggesting deficiencies in approach motivation. By middle school, this reward insensitivity is met with inadequate vagal modulation of cardiac output, suggesting additional deficiencies in emotion regulation. We propose a biosocial developmental model of conduct problems in which inherited impulsivity is amplified through social reinforcement of emotional lability. Implications for early intervention are discussed.

Dominant hemisphere lateralization of cortical parasympathetic control as revealed by frontotemporal dementia

PubMed Central

Guo, Christine C.; Sturm, Virginia E.; Zhou, Juan; Gennatas, Efstathios D.; Trujillo, Andrew J.; Hua, Alice Y.; Crawford, Richard; Stables, Lara; Kramer, Joel H.; Rankin, Katherine; Levenson, Robert W.; Rosen, Howard J.; Miller, Bruce L.; Seeley, William W.

2016-01-01

The brain continuously influences and perceives the physiological condition of the body. Related cortical representations have been proposed to shape emotional experience and guide behavior. Although previous studies have identified brain regions recruited during autonomic processing, neurological lesion studies have yet to delineate the regions critical for maintaining autonomic outflow. Even greater controversy surrounds hemispheric lateralization along the parasympathetic–sympathetic axis. The behavioral variant of frontotemporal dementia (bvFTD), featuring progressive and often asymmetric degeneration that includes the frontoinsular and cingulate cortices, provides a unique lesion model for elucidating brain structures that control autonomic tone. Here, we show that bvFTD is associated with reduced baseline cardiac vagal tone and that this reduction correlates with left-lateralized functional and structural frontoinsular and cingulate cortex deficits and with reduced agreeableness. Our results suggest that networked brain regions in the dominant hemisphere are critical for maintaining an adaptive level of baseline parasympathetic outflow. PMID:27071080

A thermosensory pathway that controls body temperature

PubMed Central

Nakamura, Kazuhiro; Morrison, Shaun F.

2008-01-01

Defending body temperature against environmental thermal challenges is one of the most fundamental homeostatic functions governed by the nervous system. Here we show a novel somatosensory pathway, which essentially constitutes the afferent arm of the thermoregulatory reflex triggered by cutaneous sensation of environmental temperature changes. Using rat in vivo electrophysiological and anatomical approaches, we revealed that lateral parabrachial neurons play a pivotal role in this pathway by glutamatergically transmitting cutaneous thermosensory signals received from spinal somatosensory neurons directly to the thermoregulatory command center, preoptic area. This feedforward pathway mediates not only sympathetic and shivering thermogenic responses but also metabolic and cardiac responses to skin cooling challenges. Notably, this ‘thermoregulatory afferent’ pathway exists in parallel with the spinothalamocortical somatosensory pathway mediating temperature perception. These findings make an important contribution to our understanding of both the somatosensory system and thermal homeostasis—two mechanisms fundamental to the nervous system and to our survival. PMID:18084288

Pathophysiologic Mechanisms in Heart Failure: Role of the Sympathetic Nervous System.

PubMed

Antoine, Steve; Vaidya, Gaurang; Imam, Haider; Villarreal, Daniel

2017-01-01

The syndrome of heart failure involves complex pathophysiologic mechanisms and is associated with extremely high-morbidity, mortality and economic costs. This growing global epidemic has diverse etiologies and is fundamentally characterized by dyshomeostasis between heart and kidneys, leading to development and progression of the cardiorenal syndrome. Excessive and sustained sympathoexcitation has emerged as a single prominent factor involved in the structural and functional dysfunction of multiple organ systems during this disease. Studies in experimental models of heart failure indicate that ablation of the renal nerves may help restore renal sodium and water equilibrium as well as the attenuation of adverse cardiac remodeling. With the recent development of minimally invasive endovascular renal denervation in humans, it is anticipated that this technology would become a novel and important paradigm shift in the management of heart failure. Copyright © 2017. Published by Elsevier Inc.

A thermosensory pathway that controls body temperature.

PubMed

Nakamura, Kazuhiro; Morrison, Shaun F

2008-01-01

Defending body temperature against environmental thermal challenges is one of the most fundamental homeostatic functions that are governed by the nervous system. Here we describe a somatosensory pathway that essentially constitutes the afferent arm of the thermoregulatory reflex that is triggered by cutaneous sensation of environmental temperature changes. Using in vivo electrophysiological and anatomical approaches in the rat, we found that lateral parabrachial neurons are pivotal in this pathway by glutamatergically transmitting cutaneous thermosensory signals received from spinal somatosensory neurons directly to the thermoregulatory command center, the preoptic area. This feedforward pathway mediates not only sympathetic and shivering thermogenic responses but also metabolic and cardiac responses to skin cooling challenges. Notably, this 'thermoregulatory afferent' pathway exists in parallel with the spinothalamocortical somatosensory pathway that mediates temperature perception. These findings make an important contribution to our understanding of both the somatosensory system and thermal homeostasis -- two mechanisms that are fundamental to the nervous system and to our survival.

Functional neuroanatomy of the central noradrenergic system.

PubMed

Szabadi, Elemer

2013-08-01

The central noradrenergic neurone, like the peripheral sympathetic neurone, is characterized by a diffusely arborizing terminal axonal network. The central neurones aggregate in distinct brainstem nuclei, of which the locus coeruleus (LC) is the most prominent. LC neurones project widely to most areas of the neuraxis, where they mediate dual effects: neuronal excitation by α₁-adrenoceptors and inhibition by α₂-adrenoceptors. The LC plays an important role in physiological regulatory networks. In the sleep/arousal network the LC promotes wakefulness, via excitatory projections to the cerebral cortex and other wakefulness-promoting nuclei, and inhibitory projections to sleep-promoting nuclei. The LC, together with other pontine noradrenergic nuclei, modulates autonomic functions by excitatory projections to preganglionic sympathetic, and inhibitory projections to preganglionic parasympathetic neurones. The LC also modulates the acute effects of light on physiological functions ('photomodulation'): stimulation of arousal and sympathetic activity by light via the LC opposes the inhibitory effects of light mediated by the ventrolateral preoptic nucleus on arousal and by the paraventricular nucleus on sympathetic activity. Photostimulation of arousal by light via the LC may enable diurnal animals to function during daytime. LC neurones degenerate early and progressively in Parkinson's disease and Alzheimer's disease, leading to cognitive impairment, depression and sleep disturbance.

Baroreflex activation therapy for the treatment of heart failure with a reduced ejection fraction: safety and efficacy in patients with and without cardiac resynchronization therapy.

PubMed

Zile, Michael R; Abraham, William T; Weaver, Fred A; Butter, Christian; Ducharme, Anique; Halbach, Marcel; Klug, Didier; Lovett, Eric G; Müller-Ehmsen, Jochen; Schafer, Jill E; Senni, Michele; Swarup, Vijay; Wachter, Rolf; Little, William C

2015-10-01

Increased sympathetic and decreased parasympathetic activity contribute to heart failure (HF) symptoms and disease progression. Carotid baroreceptor stimulation (baroreflex activation therapy, BAT) results in centrally mediated reduction of sympathetic and increase in parasympathetic activity. Because patients treated with cardiac resynchronization therapy (CRT) may have less sympathetic/parasympathetic imbalance, we hypothesized that there would be differences in the response to BAT in patients with CRT vs. those without CRT. New York Heart Association (NYHA) Class III patients with an ejection fraction (EF) ≤35% were randomized (1 : 1) to ongoing guideline-directed medical and device therapy (GDMT, control) or ongoing GDMT plus BAT. Safety endpoint was system-/procedure-related major adverse neurological and cardiovascular events (MANCE). Efficacy endpoints were Minnesota Living with Heart Failure Quality of Life (QoL), 6-min hall walk distance (6MHWD), N-terminal pro-brain natriuretic peptide (NT-proBNP), left ventricular ejection fraction (LVEF), and HF hospitalization rate. In this sample, 146 patients were randomized (70 control; 76 BAT) and were 140 activated (45 with CRT and 95 without CRT). MANCE-free rate at 6 months was 100% in CRT and 96% in no-CRT group. At 6 months, in the no-CRT group, QoL score, 6MHWD, LVEF, NT-proBNP and HF hospitalizations were significantly improved in BAT patients compared with controls. Changes in efficacy endpoints in the CRT group favoured BAT; however, the improvements were less than in the no-CRT group and were not statistically different from control. BAT is safe and significantly improved QoL, exercise capacity, NTpro-BNP, EF, and rate of HF hospitalizations in GDMT-treated NYHA Class III HF patients. These effects were most pronounced in patients not treated with CRT. © 2015 The Authors European Journal of Heart Failure © 2015 European Society of Cardiology.

Mechanisms of acute myocardial infarction study (MAMIS).

PubMed

Singh, Ram B; Pella, Daniel; Neki, Nirankar S; Chandel, J P; Rastogi, Saurabh; Mori, Heideki; Otsuka, Kuniaki; Gupta, Pankaj

2004-10-01

Acute myocardial infarction (AMI) is a highly dynamic event, which is associated with marked neuroendocrinological dysfunction in addition to cardiac damage. The immediate trigger for AMI is not precisely known. Studies conducted by Lown, Braunwald, Halberg, Otsuka and our group have demonstrated a marked increase in sympathetic activity, oxidative stress, and magnesium and potassium deficiency during AMI. Clinical studies have reported an increased incidence of AMI, sudden death and ischemia during first quarter of the day when there is a rapid withdrawal of vagal activity and increase in sympathetic tone. In one case-control study of 202 patients with AMI, there was a significant (P < 0.02) increase in cardiac events in the second quarter of the day compared to other quarters, respectively (16.8%, 41.0%, 13.8%, 28.2% per quarter). This characteristic remained prevalent in both men and women and among patients with and without known AMI (n = 52), diabetes (n = 53) or hypertension (n = 75). Triggers of AMI were noted among 162 (82.2%) of the patients. Neuropsychological mechanisms were observed as follows: emotional stress (45.5%), sleep deprivation (27.7%), cold climate (29.2%), hot climate (24.7%), large meals (47.5%) and physical exertion (31.2%). These triggering factors are known to enhance sympathetic activity and decrease vagal tone, resulting in an increased secretion of plasma cortisol, noradrenaline, aldosterone, angiotension-converting enzyme (ACE), interleukin (IL)-1, -2, -6, -18, and tumor necrosis factor-alpha (TNF-alpha), all of which are are proinflammatory agents. There is also a deficiency in the serum levels of vitamin A, E, and C and magnesium, potassium, melatonin, and IL-10 (an anti-inflammatory agent). In our study, we found a decrease in magnesium, potassium, vitamin A, E, C and beta carotene combined with an increase in thiobarbituric acid-reactive substances (TBARS), MDA and diene conjugates, TNF-alpha and IL-6, all of which are indicators of oxidative damage and proinflammatory activity, respectively.

A Non-Dimensional Analysis of Cardiovascular Response to Cold Stress. Part I. Identification of the Physical Parameters that Govern the Thermoregulatory Function of the Cardiovascular System.

DTIC Science & Technology

1983-09-01

together with an increased ventricular distensibility , tend to raise the end - 66 - diastolic volume. Again, however, :he inadequace emptying tends to... Distensibility (Sympathetic Increase, Para- sympathetic Decrease); (xi) Atrial contraction (end diastolic volume), (enhanced by sympathetic stimulation...Relationships For Striated Skeletal Muscle; Part III, Mechanics and Energetics of Muscular Contraction," Virginia Polytechnic Institute and State

Peripheral chemoreceptors and cardiorespiratory coupling: a link to sympatho-excitation.

PubMed

Zoccal, Daniel B

2015-02-01

What is the topic of this review? Chronic intermittent hypoxia (CIH), as observed in patients with obstructive sleep apnoea, is associated with the development of sympathetically mediated arterial hypertension. Nevertheless, the mechanisms underpinning the augmented sympathetic outflow in CIH still remain under investigation. What advances does it highlight? In this report, I present experimental evidence supporting the hypothesis that changes in the function of the respiratory network and coupling with the sympathetic nervous system may be considered as a novel and relevant mechanism for the increase in baseline sympathetic outflow in animals submitted to CIH. Chronic intermittent hypoxia (CIH) has been identified as a relevant risk factor for the development of enhanced sympathetic outflow and arterial hypertension. Several studies have highlighted the importance of peripheral chemoreceptors for the cardiovascular changes elicited by CIH. However, the effects of CIH on the central mechanisms regulating sympathetic outflow are not fully elucidated. Our research group has explored the hypothesis that the enhanced sympathetic drive following CIH exposure is, at least in part, dependent on alterations in the respiratory network and its interaction with the sympathetic nervous system. In this report, I discuss the changes in the discharge profile of baseline sympathetic activity in rats exposed to CIH, their association with the generation of active expiration and the interactions between expiratory and sympathetic neurones after CIH conditioning. Together, these findings are consistent with the theory that mechanisms of central respiratory-sympathetic coupling are a novel factor in the development of neurogenic hypertension. © 2014 The Authors. Experimental Physiology © 2014 The Physiological Society.

Eppur Si Muove: The Dynamic Nature of Physiological Control of Renal Blood Flow by the Renal Sympathetic Nerves

PubMed Central

Schiller, Alicia M.; Pellegrino, Peter Ricci; Zucker, Irving H.

2016-01-01

Tubuloglomerular feedback and the myogenic response are widely appreciated as important regulators of renal blood flow, but the role of the sympathetic nervous system in physiological renal blood flow control remains controversial. Where classic studies using static measures of renal blood flow failed, dynamic approaches have succeeded in demonstrating sympathetic control of renal blood flow under normal physiological conditions. This review focuses on transfer function analysis of renal pressure-flow, which leverages the physical relationship between blood pressure and flow to assess the underlying vascular control mechanisms. Studies using this approach indicate that the renal nerves are important in the rapid regulation of the renal vasculature. Animals with intact renal innervation show a sympathetic signature in the frequency range associated with sympathetic vasomotion that is eliminated by renal denervation. In conscious rabbits, this sympathetic signature exerts vasoconstrictive, baroreflex control of renal vascular conductance, matching well with the rhythmic, baroreflex-influenced control of renal sympathetic nerve activity and complementing findings from other studies employing dynamic approaches to study renal sympathetic vascular control. In this light, classic studies reporting that nerve stimulation and renal denervation do not affect static measures of renal blood flow provide evidence for the strength of renal autoregulation rather than evidence against physiological renal sympathetic control of renal blood flow. Thus, alongside tubuloglomerular feedback and the myogenic response, renal sympathetic outflow should be considered an important physiological regulator of renal blood flow. Clinically, renal sympathetic vasomotion may be important for solving the problems facing the field of therapeutic renal denervation. PMID:27514571

Eppur Si Muove: The dynamic nature of physiological control of renal blood flow by the renal sympathetic nerves.

PubMed

Schiller, Alicia M; Pellegrino, Peter Ricci; Zucker, Irving H

2017-05-01

Tubuloglomerular feedback and the myogenic response are widely appreciated as important regulators of renal blood flow, but the role of the sympathetic nervous system in physiological renal blood flow control remains controversial. Where classic studies using static measures of renal blood flow failed, dynamic approaches have succeeded in demonstrating sympathetic control of renal blood flow under normal physiological conditions. This review focuses on transfer function analysis of renal pressure-flow, which leverages the physical relationship between blood pressure and flow to assess the underlying vascular control mechanisms. Studies using this approach indicate that the renal nerves are important in the rapid regulation of the renal vasculature. Animals with intact renal innervation show a sympathetic signature in the frequency range associated with sympathetic vasomotion that is eliminated by renal denervation. In conscious rabbits, this sympathetic signature exerts vasoconstrictive, baroreflex control of renal vascular conductance, matching well with the rhythmic, baroreflex-influenced control of renal sympathetic nerve activity and complementing findings from other studies employing dynamic approaches to study renal sympathetic vascular control. In this light, classic studies reporting that nerve stimulation and renal denervation do not affect static measures of renal blood flow provide evidence for the strength of renal autoregulation rather than evidence against physiological renal sympathetic control of renal blood flow. Thus, alongside tubuloglomerular feedback and the myogenic response, renal sympathetic outflow should be considered an important physiological regulator of renal blood flow. Clinically, renal sympathetic vasomotion may be important for solving the problems facing the field of therapeutic renal denervation. Copyright © 2016 Elsevier B.V. All rights reserved.

Contributions of MSNA and stroke volume to orthostatic intolerance following bed rest

NASA Technical Reports Server (NTRS)

Shoemaker, J. K.; Hogeman, C. S.; Sinoway, L. I.

1999-01-01

We examined whether the altered orthostatic tolerance following 14 days of head-down tilt bed rest (HDBR) was related to inadequate sympathetic outflow or to excessive reductions in cardiac output during a 10- to 15-min head-up tilt (HUT) test. Heart rate, blood pressure (BP, Finapres), muscle sympathetic nerve activity (MSNA, microneurography), and stroke volume blood velocity (SVV, Doppler ultrasound) were assessed during supine 30 degrees (5 min) and 60 degrees (5-10 min) HUT positions in 15 individuals who successfully completed the pre-HDBR test without evidence of orthostatic intolerance. Subjects were classified as being orthostatically tolerant (OT, n = 9) or intolerant (OI, n = 6) following the post-HDBR test. MSNA, BP, and SVV during supine and HUT postures were not altered in the OT group. Hypotension during 60 degrees HUT in the post-bed rest test for the OI group (P < 0.05) was associated with a blunted increase in MSNA (P < 0.05). SVV was reduced following HDBR in the OI group (main effect of HDBR, P < 0.02). The data support the hypothesis that bed rest-induced orthostatic intolerance is related to an inadequate increase in sympathetic discharge that cannot compensate for a greater postural reduction in stroke volume.

Pharmacological analysis of the cardiac sympatho-inhibitory actions of moxonidine and agmatine in pithed spontaneously hypertensive rats.

PubMed

Cobos-Puc, Luis E; Sánchez-López, Araceli; Centurión, David

2016-11-15

This study shows that in spontaneously hypertensive rats (SHR) of 14-weeks-old, the sympathetically-induced, but not noradrenaline-induced tachycardic response are higher than age-matched Wistar normotensive rats. Furthermore, in SHR the sympathetically-induced tachycardic response was: (1) unaffected by moxonidine (3μg/kgmin); (2) partially inhibited by B-HT 933 (30μg/kgmin), both at the lowest doses; and (3) completely inhibited by the highest doses of B-HT 933 (100μg/kgmin), moxonidine (10μg/kgmin) or agmatine (1000 and 3000μg/kgmin) while the noradrenaline-induced tachycardic responses remained unaffected by the above compounds, except by 3000μg/kgmin agmatine. In SHR, 300μg/kg rauwolscine failed to block the sympatho-inhibition to 100μg/kgmin B-HT 933 or 10μg/kgmin moxonidine, but 1000μg/kg rauwolscine abolished, partially antagonized, and did not modify the sympatho-inhibition to the highest doses of B-HT 933, moxonidine, and agmatine, respectively, 3000μg/kg AGN 192403 or 300μg/kg BU224 given alone had no effect in the moxonidine- or agmatine-induced sympatho-inhibition, and the combination rauwolscine plus AGN 192403 but not plus BU224, abolished the sympatho-inhibition to the highest doses of moxonidine and agmatine. In conclusion, the sympathetically-induced tachycardic responses in SHR are inhibited by moxonidine and agmatine. The inhibition of moxonidine is mainly mediated by prejunctional α 2 -adrenoceptors and to a lesser extent by I 1 -imidazoline receptors, while the inhibition of agmatine is mediated by prejunctional α 2 -adrenoceptors and I 1 -imidazoline receptors at the same extent. Notwithstanding, the inhibitory function of α 2 -adrenoceptors seems to be altered in SHR compared with Wistar normotensive rats. Copyright © 2016 Elsevier B.V. All rights reserved.

Local renin–angiotensin system contributes to hyperthyroidism-induced cardiac hypertrophy

PubMed Central

Kobori, H; Ichihara, A; Miyashita, Y; Hayashi, M; Saruta, T

2008-01-01

We have reported previously that thyroid hormone activates the circulating and tissue renin–angiotensin systems without involving the sympathetic nervous system, which contributes to cardiac hypertrophy in hyperthyroidism. This study examined whether the circulating or tissue renin–angiotensin system plays the principal role in hyperthyroidism-induced cardiac hypertrophy. The circulating renin–angiotensin system in Sprague–Dawley rats was fixed by chronic angiotensin II infusion (40 ng/ min, 28 days) via mini-osmotic pumps. Daily i.p. injection of thyroxine (0·1 mg/kg per day, 28 days) was used to mimic hyperthyroidism. Serum free tri-iodothyronine, plasma renin activity, plasma angiotensin II, cardiac renin and cardiac angiotensin II were measured with RIAs. The cardiac expression of renin mRNA was evaluated by semiquantitative reverse transcriptase-polymerase chain reaction. Plasma renin activity and plasma angiotensin II were kept constant in the angiotensin II and angiotensin II+thyroxine groups (0·12 ± 0·03 and 0·15 ± 0·03 μg/h per liter, 126 ± 5 and 130 ± 5 ng/l respectively) (means ± s.e.m.). Despite stabilization of the circulating renin–angiotensin system, thyroid hormone induced cardiac hypertrophy (5·0 ± 0·5 vs 3·5 ± 0·1 mg/g) in conjunction with the increases in cardiac expression of renin mRNA, cardiac renin and cardiac angiotensin II (74 ± 2 vs 48 ± 2%, 6·5 ± 0·8 vs 3·8 ± 0·4 ng/h per g, 231 ± 30 vs 149 ± 2 pg/g respectively). These results indicate that the local renin–angiotensin system plays the primary role in the development of hyperthyroidism-induced cardiac hypertrophy. PMID:9854175

Social stress contagion in rats: Behavioural, autonomic and neuroendocrine correlates.

PubMed

Carnevali, Luca; Montano, Nicola; Statello, Rosario; Coudé, Gino; Vacondio, Federica; Rivara, Silvia; Ferrari, Pier Francesco; Sgoifo, Andrea

2017-08-01

The negative emotional consequences associated with life stress exposure in an individual can affect the emotional state of social partners. In this study, we describe an experimental rat model of social stress contagion and its effects on social behaviour and cardiac autonomic and neuroendocrine functions. Adult male Wistar rats were pair-housed and one animal (designated as "demonstrator" (DEM)) was submitted to either social defeat stress (STR) by an aggressive male Wild-type rat in a separate room or just exposed to an unfamiliar empty cage (control condition, CTR), once a day for 4 consecutive days. We evaluated the influence of cohabitation with a STR DEM on behavioural, cardiac autonomic and neuroendocrine outcomes in the cagemate (defined "observer" (OBS)). After repeated social stress, STR DEM rats showed clear signs of social avoidance when tested in a new social context compared to CTR DEM rats. Interestingly, also their cagemate STR OBSs showed higher levels of social avoidance compared to CTR OBSs. Moreover, STR OBS rats exhibited a higher heart rate and a larger shift of cardiac autonomic balance toward sympathetic prevalence (as indexed by heart rate variability analysis) immediately after the first reunification with their STR DEMs, compared to the control condition. This heightened cardiac autonomic responsiveness habituated over time. Finally, STR OBSs showed elevated plasma corticosterone levels at the end of the experimental protocol compared to CTR OBSs. These findings demonstrate that cohabitation with a DEM rat, which has experienced repeated social defeat stress, substantially disrupts social behaviour and induces short-lasting cardiac autonomic activation and hypothalamic-pituitary-adrenal axis hyperactivity in the OBS rat, thus suggesting emotional state-matching between the OBS and the DEM rats. We conclude that this rodent model may be further exploited for investigating the neurobiological bases of negative affective sharing between social partners under chronic social stress conditions. Copyright © 2017 Elsevier Ltd. All rights reserved.

Serotonin and Serotonin Transporters in the Adrenal Medulla: A Potential Hub for Modulation of the Sympathetic Stress Response.

PubMed

Brindley, Rebecca L; Bauer, Mary Beth; Blakely, Randy D; Currie, Kevin P M

2017-05-17

Serotonin (5-HT) is an important neurotransmitter in the central nervous system where it modulates circuits involved in mood, cognition, movement, arousal, and autonomic function. The 5-HT transporter (SERT; SLC6A4) is a key regulator of 5-HT signaling, and genetic variations in SERT are associated with various disorders including depression, anxiety, and autism. This review focuses on the role of SERT in the sympathetic nervous system. Autonomic/sympathetic dysfunction is evident in patients with depression, anxiety, and other diseases linked to serotonergic signaling. Experimentally, loss of SERT function (SERT knockout mice or chronic pharmacological block) has been reported to augment the sympathetic stress response. Alterations to serotonergic signaling in the CNS and thus central drive to the peripheral sympathetic nervous system are presumed to underlie this augmentation. Although less widely recognized, SERT is robustly expressed in chromaffin cells of the adrenal medulla, the neuroendocrine arm of the sympathetic nervous system. Adrenal chromaffin cells do not synthesize 5-HT but accumulate small amounts by SERT-mediated uptake. Recent evidence demonstrated that 5-HT 1A receptors inhibit catecholamine secretion from adrenal chromaffin cells via an atypical mechanism that does not involve modulation of cellular excitability or voltage-gated Ca 2+ channels. This raises the possibility that the adrenal medulla is a previously unrecognized peripheral hub for serotonergic control of the sympathetic stress response. As a framework for future investigation, a model is proposed in which stress-evoked adrenal catecholamine secretion is fine-tuned by SERT-modulated autocrine 5-HT signaling.

Differentiation in the angiotensin II receptor 1 blocker class on autonomic function.

PubMed

Krum, H

2001-09-01

Autonomic function is disordered in cardiovascular disease states such as chronic heart failure (CHF) and hypertension. Interactions between the renin-angiotensin-aldosterone system (RAAS) and the sympathetic nervous system (SNS) may potentially occur at a number of sites. These include central sites (eg, rostral ventrolateral medulla), at the level of baroreflex control, and at the sympathetic prejunctional angiotensin II receptor 1 (AT(1)) receptor, which is facilitatory for norepinephrine release from the sympathetic nerve terminal. Therefore, drugs that block the RAAS may be expected to improve autonomic dysfunction in cardiovascular disease states. In order to test the hypothesis that RAAS inhibition directly reduces SNS activity, a pithed rat model of sympathetic stimulation has been established. In this model, an increase in frequency of stimulation results in a pressor response that is sympathetically mediated and highly reproducible. This pressor response is enhanced in the presence of angiotensin II and is reduced in the presence of nonselective AIIRAs that block both AT(1) and AT(2) receptor subtypes (eg, saralasin). AT(1)-selective antagonists have also been studied in this model, at pharmacologically relevant doses. In one such study, only the AT(1) blocker eprosartan reduced sympathetically stimulated increases in blood pressure, whereas comparable doses of losartan, valsartan, and irbesartan did not. The reason(s) for the differences between eprosartan and other agents of this class on sympathetic modulation are not clear, but may relate to the chemical structure of the drug (a non- biphenyl tetrazole structure that is chemically distinct from the structure of other AIIRAs), receptor binding characteristics (competitive), or unique effects on presynaptic AT(1) receptors.

Agmatine suppresses peripheral sympathetic tone by inhibiting N-type Ca(2+) channel activity via imidazoline I2 receptor activation.

PubMed

Kim, Young-Hwan; Jeong, Ji-Hyun; Ahn, Duck-Sun; Chung, Seungsoo

2016-08-26

Agmatine, a putative endogenous ligand of imidazoline receptors, suppresses cardiovascular function by inhibiting peripheral sympathetic tone. However, the molecular identity of imidazoline receptor subtypes and its cellular mechanism underlying the agmatine-induced sympathetic suppression remains unknown. Meanwhile, N-type Ca(2+) channels are important for the regulation of NA release in the peripheral sympathetic nervous system. Therefore, it is possible that agmatine suppresses NA release in peripheral sympathetic nerve terminals by inhibiting Ca(2+) influx through N-type Ca(2+) channels. We tested this hypothesis by investigating agmatine effect on electrical field stimulation (EFS)-evoked contraction and NA release in endothelium-denuded rat superior mesenteric arterial strips. We also investigated the effect of agmatine on the N-type Ca(2+) current in superior cervical ganglion (SCG) neurons in rats. Our study demonstrates that agmatine suppresses peripheral sympathetic outflow via the imidazoline I2 receptor in rat mesenteric arteries. In addition, the agmatine-induced suppression of peripheral vascular sympathetic tone is mediated by modulating voltage-dependent N-type Ca(2+) channels in sympathetic nerve terminals. These results suggest a potential cellular mechanism for the agmatine-induced suppression of peripheral sympathetic tone. Furthermore, they provide basic and theoretical information regarding the development of new agents to treat hypertension. Copyright © 2016 Elsevier Inc. All rights reserved.

Effect of renal denervation on dynamic autoregulation of renal blood flow.

PubMed

DiBona, Gerald F; Sawin, Linda L

2004-06-01

Vasoconstrictor intensities of renal sympathetic nerve stimulation elevate the renal arterial pressure threshold for steady-state stepwise autoregulation of renal blood flow. This study examined the tonic effect of basal renal sympathetic nerve activity on dynamic autoregulation of renal blood flow in rats with normal (Sprague-Dawley and Wistar-Kyoto) and increased levels of renal sympathetic nerve activity (congestive heart failure and spontaneously hypertensive rats). Steady-state values of arterial pressure and renal blood flow before and after acute renal denervation were subjected to transfer function analysis. Renal denervation increased basal renal blood flow in congestive heart failure (+35 +/- 3%) and spontaneously hypertensive rats (+21 +/- 3%) but not in Sprague-Dawley and Wistar-Kyoto rats. Renal denervation significantly decreased transfer function gain (i.e., improved autoregulation of renal blood flow) and increased coherence only in spontaneously hypertensive rats. Thus vasoconstrictor intensities of renal sympathetic nerve activity impaired the dynamic autoregulatory adjustments of the renal vasculature to oscillations in arterial pressure. Renal denervation increased renal blood flow variability in spontaneously hypertensive rats and congestive heart failure rats. The contribution of vasoconstrictor intensities of basal renal sympathetic nerve activity to limiting renal blood flow variability may be important in the stabilization of glomerular filtration rate.

Gravitational force and the cardiovascular system

NASA Technical Reports Server (NTRS)

Pendergast, D. R.; Olszowka, A. J.; Rokitka, M. A.; Farhi, L. E.

1991-01-01

Ground-based simulation studies have been conducted to clarify the problems of the cardiovascular adaptation to alterations in gravitational force. Simulated microgravity experiments resulted in increases in cardiac stretch, urine flow, and sodium excretion, which were accompanied by lower plasma renin, aldosterone, and ADH. There appears to be a decrease in plasma volume as well as in sympathetic tone after 2-3 days of 0 Gz. Complete adjustment to 0 Gz is found within 8 h without a decrease in plasma volume, when subjects are allowed to dehydrate mildly.

Cardiorespiratory effects of inelastic chest wall restriction.

PubMed

Miller, Jordan D; Beck, Kenneth C; Joyner, Michael J; Brice, A Glenn; Johnson, Bruce D

2002-06-01

We examined the effects of chest wall restriction (CWR) on cardiorespiratory function at rest and during exercise in healthy subjects in an attempt to approximate the cardiorespiratory interactions observed in clinical conditions that result in restrictive lung and/or chest wall changes and a reduced intrathoracic space. Canvas straps were applied around the thorax and abdomen so that vital capacity was reduced by >35%. Data were acquired at rest and during cycle ergometry at 25 and 45% of peak workloads. CWR elicited significant increases in the flow-resistive work performed on the lung (160%) and the gastric pressure-time integral (>400%) at the higher workload, but it resulted in a decrease in the elastic work performed on the lung (56%) compared with control conditions. With CWR, heart rate increased and stroke volume (SV) fell, resulting in >10% fall in cardiac output at rest and during exercise at matched workloads (P < 0.05). Blood pressure and catecholamines were significantly elevated during CWR exercise conditions (P < 0.05). We conclude that CWR significantly impairs SV during exercise and that a compensatory increase in heart rate does not prevent a significant reduction in cardiac output. O(2) consumption appears to be maintained via increased extraction and a redistribution of blood flow via sympathetic activation.

Heart rate and blood pressure variabilities in salt-sensitive hypertension.

PubMed

Piccirillo, G; Bucca, C; Durante, M; Santagada, E; Munizzi, M R; Cacciafesta, M; Marigliano, V

1996-12-01

In salt-sensitive hypertension, a high sodium intake causes plasma catecholamines to rise and pulmonary baroreceptor plasticity to fall. In salt-sensitive and salt-resistant hypertensive subjects during low and high sodium intakes, we studied autonomic nervous system activity by power spectral analysis of heart rate and arterial pressure variabilities and baroreceptor sensitivity. In all subjects, high sodium intake significantly enhanced the low-frequency power of heart rate and arterial pressures at rest and after sympathetic stress. It also increased heart rate and arterial pressure variabilities. During high sodium intake, salt-sensitive hypertensive subjects had significantly higher low-frequency powers of systolic arterial pressure (7.5 mm Hg2, P < .05) and of heart rate at rest (59.2 +/- 2.4 normalized units [NU], P < .001) than salt-resistant subjects (6.6 +/- 0.3 mm Hg2, 55.0 +/- 3.2 NU) and normotensive control subjects (5.1 +/- 0.5 mm Hg2, 41.6 +/- 2.9 NU). In salt-sensitive subjects, low sodium intake significantly reduced low-frequency normalized units (P < .001) and the ratio of low- to high-power frequency (P < .001). High-sodium intake significantly increased baroreflex sensitivity in control subjects (from 10.0 +/- 0.7 to 17.5 +/- 0.7 ms/mm Hg, P < .001) and salt-resistant subjects (from 6.9 +/- 0.7 to 13.9 +/- 0.9, P < .05) but not in salt-sensitive subjects (7.4 +/- 0.3 to 7.9 +/- 0.4). In conclusion, a high sodium intake markedly enhances cardiac sympathetic activity in salt-sensitive and salt-resistant hypertension. In contrast, although reduced sodium intake lowers arterial pressure and sympathetic activity, it does so only in salt-sensitive subjects. Hence, in salt-resistant subjects, neither arterial pressure nor sympathetic activity depends on salt intake. During a high sodium intake in normotensive subjects and salt-resistant hypertensive subjects, increased sympathetic activity is probably compensated by enhanced baroreflex sensitivity.

Actions of rilmenidine on neurogenic hypertension in BPH/2J genetically hypertensive mice.

PubMed

Jackson, Kristy L; Palma-Rigo, Kesia; Nguyen-Huu, Thu-Phuc; Davern, Pamela J; Head, Geoffrey A

2014-03-01

BPH/2J hypertensive mice have an exaggerated sympathetic contribution to blood pressure (BP). Premotor sympathetic neurons within the rostroventrolateral medulla (RVLM) are a major source of sympathetic vasomotor tone and major site of action of the centrally acting sympatholytic agent, rilmenidine. The relative cardiovascular effect of rilmenidine in BPH/2J versus normotensive BPN/3J mice was used as an indicator of the involvement of the RVLM in the sympathetic contribution to hypertension in BPH/2J mice. BPH/2J and BPN/3J mice were pre-implanted with telemetry devices to measure BP in conscious unrestrained mice. Rilmenidine was administered acutely (n=7-9/group), orally for 14 days, at a wide range of doses (n=5/group), and also infused intracerebroventricularly for 7 days (n=6/group). Acute intraperitoneal rilmenidine induced greater depressor and bradycardic responses in BPH/2J than BPN/3J mice (Pstrain<0.01). Both responses were reduced by atropine pre-treatment, with the remaining hypotensive effect being small and comparable between strains (Pstrain=1.0). This suggests that vagally induced reductions in cardiac output were responsible for the hypotension. Chronic intracerebroventricularly infused rilmenidine reduced BP from baseline marginally in BPH/2J mice during the dark (active) period (-6.5 ± 2 mmHg; P=0.006). Chronic orally administered rilmenidine (1-12 mg/kg per day) also had minimal effect on 24-h BP in both strains (P>0.16). The sympathetic vasomotor inhibitory effect of rilmenidine is minimal in both strains and similar in hypertensive BPH/2J and BPN/3J mice. Thus, hypertension in BPH/2J mice is not likely mediated by greater neuronal activity in the RVLM, and agents such as rilmenidine would be an ineffective treatment for this form of neurogenic hypertension.

Cirrhotic cardiomyopathy: Implications for the perioperative management of liver transplant patients

PubMed Central

Rahman, Suehana; Mallett, Susan V

2015-01-01

Cirrhotic cardiomyopathy is a disease that has only recently been recognised as a definitive clinical entity. In the setting of liver cirrhosis, it is characterized by a blunted inotropic and chronotropic response to stress, impaired diastolic relaxation of the myocardium and prolongation of the QT interval in the absence of other known cardiac disease. A key pathological feature is the persistent over-activation of the sympathetic nervous system in cirrhosis, which leads to down-regulation and dysfunction of the β-adrenergic receptor. Diagnosis can be made using a combination of echocardiography (resting and stress), tissue Doppler imaging, cardiac magnetic resonance imaging, 12-lead electrocardiogram and measurement of biomarkers. There are significant implications of cirrhotic cardiomyopathy in a number of clinical situations in which there is an increased physiological demand, which can lead to acute cardiac decompensation and heart failure. Prior to transplantation there is an increased risk of hepatorenal syndrome, cardiac failure following transjugular intrahepatic portosystemic shunt insertion and increased risk of arrhythmias during acute gastrointestinal bleeding. Liver transplantation presents the greatest physiological challenge with a further risk of acute cardiac decompensation. Peri-operative management should involve appropriate choice of graft and minimization of large fluctuations in preload and afterload. The avoidance of cardiac failure during this period has important prognostic implications, as there is evidence to suggest a long-term resolution of the abnormalities in cirrhotic cardiomyopathy. PMID:25848474

Cardiac mast cell-derived renin promotes local angiotensin formation, norepinephrine release, and arrhythmias in ischemia/reperfusion.

PubMed

Mackins, Christina J; Kano, Seiichiro; Seyedi, Nahid; Schäfer, Ulrich; Reid, Alicia C; Machida, Takuji; Silver, Randi B; Levi, Roberto

2006-04-01

Having identified renin in cardiac mast cells, we assessed whether its release leads to cardiac dysfunction. In Langendorff-perfused guinea pig hearts, mast cell degranulation with compound 48/80 released Ang I-forming activity. This activity was blocked by the selective renin inhibitor BILA2157, indicating that renin was responsible for Ang I formation. Local generation of cardiac Ang II from mast cell-derived renin also elicited norepinephrine release from isolated sympathetic nerve terminals. This action was mediated by Ang II-type 1 (AT1) receptors. In 2 models of ischemia/reperfusion using Langendorff-perfused guinea pig and mouse hearts, a significant coronary spillover of renin and norepinephrine was observed. In both models, this was accompanied by ventricular fibrillation. Mast cell stabilization with cromolyn or lodoxamide markedly reduced active renin overflow and attenuated both norepinephrine release and arrhythmias. Similar cardioprotection was observed in guinea pig hearts treated with BILA2157 or the AT1 receptor antagonist EXP3174. Renin overflow and arrhythmias in ischemia/reperfusion were much less prominent in hearts of mast cell-deficient mice than in control hearts. Thus, mast cell-derived renin is pivotal for activating a cardiac renin-angiotensin system leading to excessive norepinephrine release in ischemia/reperfusion. Mast cell-derived renin may be a useful therapeutic target for hyperadrenergic dysfunctions, such as arrhythmias, sudden cardiac death, myocardial ischemia, and congestive heart failure.

Baroreflex Activation Therapy in Congestive Heart Failure: Novel Findings and Future Insights.

PubMed

Grassi, Guido; Brambilla, GianMaria; Pizzalla, Daniela Prata; Seravalle, Gino

2016-08-01

Congestive heart failure is characterized by hemodynamic and non-hemodynamic abnormalities, the latter including an activation of the sympathetic influences to the heart and peripheral circulation coupled with an impairment of baroreceptor control of autonomic function. Evidence has been provided that both these alterations are hallmark features of the disease with a specific relevance for the disease progression as well as for the development of life-threatening cardiac arrhythmias. In addition, a number of studies have documented in heart failure the adverse prognostic role of the sympathetic and baroreflex alterations, which both are regarded as major independent determinants of cardiovascular morbidity and mortality. This represents the pathophysiological and clinical background for the use of carotid baroreceptor activation therapy in the treatment of congestive heart failure. Promising data collected in experimental animal models of heart failure have supported the recent performance of pilot small-scale clinical studies, aimed at providing initial information in this area. The results of these studies demonstrated the clinical safety and efficacy of the intervention which has been tested in large-scale clinical studies. The present paper will critically review the background and main results of the published studies designed at defining the clinical impact of baroreflex activation therapy in congestive heart failure patients. Emphasis will be given to the strengths and limitations of such studies, which represent the background for the ongoing clinical trials testing the long-term effects of the device in heart failure patients.

Accentuated antagonism in vagal heart rate control mediated through muscarinic potassium channels.

PubMed

Mizuno, Masaki; Kamiya, Atsunori; Kawada, Toru; Miyamoto, Tadayoshi; Shimizu, Shuji; Shishido, Toshiaki; Sugimachi, Masaru

2008-12-01

Although muscarinic K(+) (K(ACh)) channels contribute to a rapid heart rate (HR) response to vagal stimulation, whether background sympathetic tone affects the HR control via the K(ACh)channels remains to be elucidated. In seven anesthetized rabbits with sinoaortic denervation and vagotomy, we estimated the dynamic transfer function of the HR response by using random binary vagal stimulation (0-10 Hz). Tertiapin, a selective K(ACh) channel blocker, decreased the dynamic gain (to 2.3+/- 0.9 beats.min(-1).Hz(-1), from 4.6+/- 1.1, P < 0.01, mean+/- SD) and the corner frequency (to 0.05+/- 0.01 Hz, from 0.26+/- 0.04, P < 0.01). Under 5 Hz tonic cardiac sympathetic stimulation (CSS), tertiapin decreased the dynamic gain (to 3.6+/- 1.0 beats.min(-1).Hz(-1), from 7.3+/- 1.1, P < 0.01) and the corner frequency (to 0.06+/- 0.02 Hz, from 0.23+/- 0.06, P < 0.01). Two-way analysis of variance indicated significant interaction between the tertiapin and CSS effects on the dynamic gain. In contrast, no significant interactions were observed between the tertiapin and CSS effects on the corner frequency and the lag time. In conclusion, although a cyclic AMP-dependent mechanism has been well established, an accentuated antagonism also occurred in the direct effect of ACh via the K(ACh) channels. The rapidity of the HR response obtained by the K(ACh) channel pathway was robust during the accentuated antagonism.

Differentiation in the effects of the angiotensin II receptor blocker class on autonomic function.

PubMed

Esler, Murray

2002-06-01

Measurement of regional sympathetic activity with nerve recording and noradrenaline spillover isotope dilution techniques demonstrates activation of the sympathetic nerves of the heart, kidneys and skeletal muscle vasculature in younger patients with essential hypertension. Sympathetic overactivity in the renal sympathetic outflow is a prominent pathophysiological feature in obesity-related hypertensives of any age. This increase in sympathetic activity is thought to both initiate and sustain the blood pressure elevation, and, in addition, contributes to adverse cardiovascular events. Sympathetic overactivity seems to particularly influence systolic pressure, by increasing the rate of left ventricular ejection, by reducing arterial compliance through increasing neural arterial tone, and via arteriolar vasoconstriction, by promoting rebound of the reflected arterial wave from the periphery. Inhibition of the renin-angiotensin system in certain circumstances appears to be able to reduce sympathetic nervous activity. Claims have been made for such an action at virtually every site in the sympathetic neuraxis. In reality, renin-angiotensin actions on the sympathetic nervous system are probably much more circumscribed than this, with the case perhaps being strongest for a presynaptic action of angiotensin on sympathetic nerves, to augment noradrenaline release. The ability of angiotensin receptor blockers to antagonize neural presynaptic angiotensin AT1 receptors appears to differ markedly between the individual agents in this drug class. In experimental models, such as the pithed rat, neural presynaptic actions are particularly evident with eprosartan. In a blinded study of crossover design, the effects of eprosartan and losartan on sympathetic nerve firing, measured by microneurography, and whole body noradrenaline spillover to plasma is currently being measured in patients with essential hypertension. A reduction in noradrenaline spillover disproportionate to any possible fall in nerve firing would document the presence of presynaptic antagonism of noradrenaline release.

Retention Kinetics of the 18F-Labeled Sympathetic Nerve PET Tracer LMI1195: Comparison with 11C-Hydroxyephedrine and 123I-MIBG.

PubMed

Werner, Rudolf A; Rischpler, Christoph; Onthank, David; Lapa, Constantin; Robinson, Simon; Samnick, Samuel; Javadi, Mehrbod; Schwaiger, Markus; Nekolla, Stephan G; Higuchi, Takahiro

2015-09-01

(18)F-N-[3-bromo-4-(3-fluoro-propoxy)-benzyl]-guanidine ((18)F-LMI1195) is a new PET tracer designed for noninvasive assessment of sympathetic innervation of the heart. The (18)F label facilitates the imaging advantages of PET over SPECT technology while allowing centralized manufacturing. Highly specific neural uptake of (18)F-LMI1195 has previously been established, but the retention kinetics are not yet fully understood. Healthy New Zealand White rabbits were studied with (18)F-LMI1195 using a small-animal PET system. Dynamic 40-min chest scans were started just before intravenous bolus injection of (18)F-LMI1195. Imaging was performed under norepinephrine transport inhibition with desipramine pretreatment, a 1.5 mg/kg desipramine chase administered 10 min after tracer injection, and saline treatment of controls. As a reference, cardiac uptake of (11)C-hydroxyephedrine and (123)I-metaiodobenzylguanidine ((123)I-MIBG) was examined by PET and planar scintigraphy, respectively. Cardiac uptake of all 3 tracers was inhibited by pretreatment with desipramine. Stable cardiac tracer retention was delineated by dynamic PET in control rabbits for (11)C-hydroxyephedrine (washout rate, 0.42% ± 0.57%/min) and (18)F-LMI1195 (washout rate, 0.058% ± 0.28%/min). A desipramine chase increased (11)C-hydroxyephedrine washout from the heart (2.43% ± 0.15%/min, P < 0.001), whereas (18)F-LMI1195 washout was not influenced (0.059% ± 0.11%/min, not statistically significant). Additionally, a desipramine chase did not change the cardiac (123)I-MIBG uptake (delayed heart-to-mediastinum ratio, 1.99 ± 0.12 (desipramine chase) vs. 2.05 ± 0.16 (controls), not statistically significant). In vivo norepinephrine transporter (NET) blockade with desipramine confirmed specific neural uptake of (18)F-LMI1195, (11)C-hydroxyephedrine, and (123)I-MIBG in rabbit hearts. (11)C-hydroxyephedrine cardiac retention was sensitive to a NET inhibitor chase, indicating a cycle of continuous NET uptake and release at the nerve terminals. In contrast, (18)F-LMI1195 and (123)I-MIBG demonstrated stable storage at the nerve terminal with resistance to a NET inhibitor chase, mimicking physiologic norepinephrine turnover. © 2015 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Chronic infusion of enalaprilat into hypothalamic paraventricular nucleus attenuates angiotensin II-induced hypertension and cardiac hypertrophy by restoring neurotransmitters and cytokines

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kang, Yu-Ming, E-mail: ykang@mail.xjtu.edu.cn; Zhang, Dong-Mei; Yu, Xiao-Jing

The renin–angiotensin system (RAS) in the brain is involved in the pathogenesis of hypertension. We hypothesized that inhibition of angiotensin-converting enzyme (ACE) in the hypothalamic paraventricular nucleus (PVN) attenuates angiotensin II (ANG II)-induced hypertension via restoring neurotransmitters and cytokines. Rats underwent subcutaneous infusions of ANG II or saline and bilateral PVN infusions of ACE inhibitor enalaprilat (ENL, 2.5 μg/h) or vehicle for 4 weeks. ANG II infusion resulted in higher mean arterial pressure and cardiac hypertrophy as indicated by increased whole heart weight/body weight ratio, whole heart weight/tibia length ratio, left ventricular weight/tibia length ratio, and mRNA expressions of cardiacmore » atrial natriuretic peptide and beta-myosin heavy chain. These ANG II-infused rats had higher PVN levels of glutamate, norepinephrine, tyrosine hydroxylase, pro-inflammatory cytokines (PICs) and the chemokine monocyte chemoattractant protein-1, and lower PVN levels of gamma-aminobutyric acid, interleukin (IL)-10 and the 67-kDa isoform of glutamate decarboxylase (GAD67), and higher plasma levels of PICs, norepinephrine and aldosterone, and lower plasma IL-10, and higher renal sympathetic nerve activity. However, PVN treatment with ENL attenuated these changes. PVN microinjection of ANG II induced increases in IL-1β and IL-6, and a decrease in IL-10 in the PVN, and pretreatment with angiotensin II type 1 receptor (AT1-R) antagonist losartan attenuated these changes. These findings suggest that ANG II infusion induces an imbalance between excitatory and inhibitory neurotransmitters and an imbalance between pro- and anti-inflammatory cytokines in the PVN, and PVN inhibition of the RAS restores neurotransmitters and cytokines in the PVN, thereby attenuating ANG II-induced hypertension and cardiac hypertrophy. - Highlights: • Chronic ANG II infusion results in sympathetic hyperactivity and cardiac hypertrophy. • PVN inhibition of ACE attenuates ANG II-induced hypertension and cardiac hypertrophy. • PVN inhibition of ACE attenuates ANG II-induced imbalance of PVN neurotransmitters. • PVN inhibition of ACE attenuates ANG II-induced imbalance of cytokines in the PVN. • PVN blockade of AT1-R attenuates ANG II-induced imbalance of cytokines in the PVN.« less

Statistical coding and decoding of heartbeat intervals.

PubMed

Lucena, Fausto; Barros, Allan Kardec; Príncipe, José C; Ohnishi, Noboru

2011-01-01

The heart integrates neuroregulatory messages into specific bands of frequency, such that the overall amplitude spectrum of the cardiac output reflects the variations of the autonomic nervous system. This modulatory mechanism seems to be well adjusted to the unpredictability of the cardiac demand, maintaining a proper cardiac regulation. A longstanding theory holds that biological organisms facing an ever-changing environment are likely to evolve adaptive mechanisms to extract essential features in order to adjust their behavior. The key question, however, has been to understand how the neural circuitry self-organizes these feature detectors to select behaviorally relevant information. Previous studies in computational perception suggest that a neural population enhances information that is important for survival by minimizing the statistical redundancy of the stimuli. Herein we investigate whether the cardiac system makes use of a redundancy reduction strategy to regulate the cardiac rhythm. Based on a network of neural filters optimized to code heartbeat intervals, we learn a population code that maximizes the information across the neural ensemble. The emerging population code displays filter tuning proprieties whose characteristics explain diverse aspects of the autonomic cardiac regulation, such as the compromise between fast and slow cardiac responses. We show that the filters yield responses that are quantitatively similar to observed heart rate responses during direct sympathetic or parasympathetic nerve stimulation. Our findings suggest that the heart decodes autonomic stimuli according to information theory principles analogous to how perceptual cues are encoded by sensory systems.

Effect of Methamphetamine Dependence on Heart Rate Variability

PubMed Central

Henry, Brook L.; Minassian, Arpi; Perry, William

2010-01-01

Background Methamphetamine (METH) is an increasing popular and highly addictive stimulant associated with autonomic nervous system (ANS) dysfunction, cardiovascular pathology, and neurotoxicity. Heart rate variability (HRV) has been used to assess autonomic function and predict mortality in cardiac disorders and drug intoxication, but has not been characterized in METH use. We recorded HRV in a sample of currently abstinent individuals with a history of METH dependence compared to age- and gender-matched drug-free comparison subjects. Method HRV was assessed using time domain, frequency domain, and nonlinear entropic analyses in 17 previously METH-dependent and 21 drug-free comparison individuals during a 5 minute rest period. Results The METH-dependent group demonstrated significant reduction in HRV, reduced parasympathetic activity, and diminished heartbeat complexity relative to comparison participants. More recent METH use was associated with increased sympathetic tone. Conclusion Chronic METH exposure may be associated with decreased HRV, impaired vagal function, and reduction in heart rate complexity as assessed by multiple methods of analysis. We discuss and review evidence that impaired HRV may be related to the cardiotoxic or neurotoxic effects of prolonged METH use. PMID:21182570

The Difference Between Exercise-Induced Autonomic and Fitness Changes Measured After 12 and 20 Weeks of Medium-to-High Intensity Military Training.

PubMed

Grant, Catharina C; Mongwe, Lot; Janse van Rensburg, Dina C; Fletcher, Lizelle; Wood, Paola S; Terblanche, Etrisia; du Toit, Peet J

2016-09-01

Grant, CC, Mongwe, L, Janse van Rensburg, DC, Fletcher, L, Wood, PS, Terblanche, E, and du Toit, PJ. The difference between exercise-induced autonomic and fitness changes measured after 12 and 20 weeks of medium-to-high intensity military training. J Strength Cond Res 30(9): 2453-2459, 2016-The aim of this study was to compare the physical fitness, based on VO2max and exercise-induced cardiac autonomic changes, measured by heart rate variability (HRV) of 12 weeks with 20 weeks of training in the South African National Defence Force. Recruits (n = 154) participated in a medium-to-high intensity exercise intervention (daily energy expenditure: 8,485 kJ·d). The significant effect on VO2max between weeks 1 and 12 (48.57, SD = 9.25 vs. 53.36, SD = 7.21] did not continue during weeks 12-20 (53.36, SD = 7.21 vs. 53.87, SD = 7.87). No changes in the supine low frequency (LF)/high frequency (HF) (0.48, SD = 0.51 vs. 0.41, SD = 0.64) or the standing LF/HF (4.02, SD = 5.14 vs. 3.91, SD = 5.28), an indicator of autonomic balance and a possible indicator of overtraining syndrome, suggests that overtraining did not take place during weeks 12-20. This was confirmed with further decreases in supine and standing heart rate. However, the power of the vagal-induced variability continued to increase after 12 weeks. Increased vagal influence without concurrent change in autonomic balance may be interpreted as decreased sympathetic cardiac control. It is important to note that although no fitness changes were detected, positive cardiac autonomic conditioning did continue between weeks 12 and 20, as measured by increased vagal-induced HRV and decreased sympathetic influence on cardiac control. Results may be extrapolated to training in the normal population/athletes after a medium-to-high intensity exercise program, as this intervention was a closely monitored and standardized exercise program.

Ghrelin and the cardiovascular system.

PubMed

Tokudome, Takeshi; Kishimoto, Ichiro; Miyazato, Mikiya; Kangawa, Kenj

2014-01-01

Ghrelin is a peptide that was originally isolated from the stomach. It exerts potent growth hormone (GH)-releasing and orexigenic activities. Several studies have highlighted the therapeutic benefits of ghrelin for the treatment of cardiovascular disease. In animal models of chronic heart failure, the administration of ghrelin improved cardiac function and remodeling; these findings were replicated in human patients with heart failure. Moreover, in an animal study, ghrelin administration effectively reduced pulmonary hypertension induced by chronic hypoxia. In addition, repeated administration of ghrelin to cachectic patients with chronic obstructive pulmonary disease had positive effects on overall body function, including muscle wasting, functional capacity and sympathetic activity. The administration of ghrelin early after myocardial infarction (MI) reduced fatal arrhythmia and related mortality. In ghrelin-deficient mice, both exogenous and endogenous ghrelin were protective against fatal arrhythmia and promoted remodeling after MI. Although the mechanisms underlying the effects of ghrelin on the cardiovascular system remain unclear, there are indications that its beneficial effects are mediated through both direct physiological actions, including increased GH levels, improved energy balance and direct actions on cardiovascular cells, and regulation of autonomic nervous system activity. Therefore, ghrelin is a promising novel therapeutic agent for cardiovascular disease. © 2014 S. Karger AG, Basel.

Vascular dysfunctions following spinal cord injury

PubMed Central

Popa, F; Grigorean, VT; Onose, G; Sandu, AM; Popescu, M; Burnei, G; Strambu, V; Sinescu, C

2010-01-01

The aim of this article is to analyze the vascular dysfunctions occurring after spinal cord injury (SCI). Vascular dysfunctions are common complications of SCI. Cardiovascular disturbances are the leading causes of morbidity and mortality in both acute and chronic stages of SCI. Neuroanatomy and physiology of autonomic nervous system, sympathetic and parasympathetic, is reviewed. SCI implies disruption of descendent pathways from central centers to spinal sympathetic neurons, originating in intermediolateral nuclei of T1–L2 cord segments. Loss of supraspinal control over sympathetic nervous system results in reduced overall sympathetic activity below the level of injury and unopposed parasympathetic outflow through intact vagal nerve. SCI associates significant vascular dysfunction. Spinal shock occurs during the acute phase following SCI and it is a transitory suspension of function and reflexes below the level of the injury. Neurogenic shock, part of spinal shock, consists of severe arterial hypotension and bradycardia. Autonomic dysreflexia appears during the chronic phase, after spinal shock resolution, and it is a life–threatening syndrome of massive imbalanced reflex sympathetic discharge occurring in patients with SCI above the splanchnic sympathetic outflow (T5–T6). Arterial hypotension with orthostatic hypotension occurs in both acute and chronic phases. The etiology is multifactorial. We described a few factors influencing the orthostatic hypotension occurrence in SCI: sympathetic nervous system dysfunction, low plasma catecholamine levels, rennin–angiotensin–aldosterone activity, peripheral alpha–adrenoceptor hyperresponsiveness, impaired function of baroreceptors, hyponatremia and low plasmatic volume, cardiovascular deconditioning, morphologic changes in sympathetic neurons, plasticity within spinal circuits, and motor deficit leading to loss of skeletal muscle pumping activity. Additional associated cardiovascular concerns in SCI, such as deep vein thrombosis and long–term risk for coronary heart disease and systemic atherosclerosis are also described. Proper prophylaxis, including non–pharmacologic and pharmacological strategies, diminishes the occurrence of the vascular dysfunction following SCI. Each vascular disturbance requires a specific treatment. PMID:20945818

Influence of computer work under time pressure on cardiac activity.

PubMed

Shi, Ping; Hu, Sijung; Yu, Hongliu

2015-03-01

Computer users are often under stress when required to complete computer work within a required time. Work stress has repeatedly been associated with an increased risk for cardiovascular disease. The present study examined the effects of time pressure workload during computer tasks on cardiac activity in 20 healthy subjects. Heart rate, time domain and frequency domain indices of heart rate variability (HRV) and Poincaré plot parameters were compared among five computer tasks and two rest periods. Faster heart rate and decreased standard deviation of R-R interval were noted in response to computer tasks under time pressure. The Poincaré plot parameters showed significant differences between different levels of time pressure workload during computer tasks, and between computer tasks and the rest periods. In contrast, no significant differences were identified for the frequency domain indices of HRV. The results suggest that the quantitative Poincaré plot analysis used in this study was able to reveal the intrinsic nonlinear nature of the autonomically regulated cardiac rhythm. Specifically, heightened vagal tone occurred during the relaxation computer tasks without time pressure. In contrast, the stressful computer tasks with added time pressure stimulated cardiac sympathetic activity. Copyright © 2015 Elsevier Ltd. All rights reserved.

Blood pressure responses to dietary sodium: Association with autonomic cardiovascular function in normotensive adults.

PubMed

Matthews, Evan L; Brian, Michael S; Edwards, David G; Stocker, Sean D; Wenner, Megan M; Farquhar, William B

2017-12-01

Blood pressure responses to dietary sodium vary widely person-to-person. Salt sensitive rodent models display altered autonomic function, a trait thought to contribute to poor cardiovascular health. Thus, we hypothesized that increased salt sensitivity (SS) in normotensive humans would be associated with increased muscle sympathetic nerve activity (MSNA), decreased high frequency heart rate variability (HF-HRV), and decreased baroreflex sensitivity. Healthy normotensive men and women completed 1week of high (300mmol·day -1 ) and 1week of low (20mmol·day -1 ) dietary sodium (random order) with 24h mean arterial pressure (MAP) assessed on the last day of each diet to assess SS. Participants returned to the lab under habitual sodium conditions for testing. Forty-two participants are presented in this analysis, 19 of which successful MSNA recordings were obtained (n=42: age 39±2yrs., BMI 24.3±0.5kg·(m 2 ) -1 , MAP 83±1mmHg, habitual urine sodium 93±7mmol·24h -1 ; n=19: MSNA burst frequency 20±2 bursts·min -1 ). The variables of interest were linearly regressed over the magnitude of SS. Higher SS was associated with increased MSNA (burst frequency: r=0.469, p=0.041), decreased HF-HRV (r=-0.349, p=0.046), and increased LF/HF-HRV (r=0.363, p=0.034). SS was not associated with sympathetic or cardiac baroreflex sensitivity (p>0.05). Multiple regression analysis accounting for age found that age, not SS, independently predicted HF-HRV (age adjusted no longer significant; p=0.369) and LF/HF-HRV (age adjusted p=0.273). These data suggest that age-related salt sensitivity of blood pressure in response to dietary sodium is associated with altered resting autonomic cardiovascular function. Copyright © 2017 Elsevier B.V. All rights reserved.

Heart rate variability in normal and pathological sleep.

PubMed

Tobaldini, Eleonora; Nobili, Lino; Strada, Silvia; Casali, Karina R; Braghiroli, Alberto; Montano, Nicola

2013-10-16

Sleep is a physiological process involving different biological systems, from molecular to organ level; its integrity is essential for maintaining health and homeostasis in human beings. Although in the past sleep has been considered a state of quiet, experimental and clinical evidences suggest a noteworthy activation of different biological systems during sleep. A key role is played by the autonomic nervous system (ANS), whose modulation regulates cardiovascular functions during sleep onset and different sleep stages. Therefore, an interest on the evaluation of autonomic cardiovascular control in health and disease is growing by means of linear and non-linear heart rate variability (HRV) analyses. The application of classical tools for ANS analysis, such as HRV during physiological sleep, showed that the rapid eye movement (REM) stage is characterized by a likely sympathetic predominance associated with a vagal withdrawal, while the opposite trend is observed during non-REM sleep. More recently, the use of non-linear tools, such as entropy-derived indices, have provided new insight on the cardiac autonomic regulation, revealing for instance changes in the cardiovascular complexity during REM sleep, supporting the hypothesis of a reduced capability of the cardiovascular system to deal with stress challenges. Interestingly, different HRV tools have been applied to characterize autonomic cardiac control in different pathological conditions, from neurological sleep disorders to sleep disordered breathing (SDB). In summary, linear and non-linear analysis of HRV are reliable approaches to assess changes of autonomic cardiac modulation during sleep both in health and diseases. The use of these tools could provide important information of clinical and prognostic relevance.

Sympathetic nervous system and the kidney in hypertension.

PubMed

DiBona, Gerald F

2002-03-01

Long-term control of arterial pressure has been attributed to the kidney by virtue of its ability to couple the regulation of blood volume to the maintenance of sodium and water balance by the mechanisms of pressure natriuresis and diuresis. In the presence of a defect in renal excretory function, hypertension arises as the consequence of the need for an increase in arterial pressure to offset the abnormal pressure natriuresis and diuresis mechanisms, and to maintain sodium and water balance. There is growing evidence that an important cause of the defect in renal excretory function in hypertension is an increase in renal sympathetic nerve activity (RSNA). First, increased RSNA is found in animal models of hypertension and hypertensive humans. Second, renal denervation prevents or alleviates hypertension in virtually all animal models of hypertension. Finally, increased RSNA results in reduced renal excretory function by virtue of effects on the renal vasculature, the tubules, and the juxtaglomerular granular cells. The increase in RSNA is of central nervous system origin, with one of the stimuli being the action of angiotensin II, probably of central origin. By acting on brain stem nuclei that are important in the control of peripheral sympathetic vasomotor tone (e.g. rostral ventrolateral medulla), angiotensin II increases the basal level of RSNA and impairs its arterial baroreflex regulation. Therefore, the renal sympathetic nerves may serve as the link between central sympathetic nervous system regulatory sites and the kidney in contributing to the renal excretory defect in the development of hypertension.

[Role of the sympathetic nervous system in vasovagal syncope and rationale for beta-blockers and norepinephrine transporter inhibitors].

PubMed

Márquez, Manlio F; Gómez-Flores, Jorge Rafael; González-Hermosillo, Jesús A; Ruíz-Siller, Teresita de Jesús; Cárdenas, Manuel

2016-12-29

Vasovagal or neurocardiogenic syncope is a common clinical situation and, as with other entities associated with orthostatic intolerance, the underlying condition is a dysfunction of the autonomic nervous system. This article reviews various aspects of vasovagal syncope, including its relationship with orthostatic intolerance and the role of the autonomic nervous system in it. A brief history of the problem is given, as well as a description of how the names and associated concepts have evolved. The response of the sympathetic system to orthostatic stress, the physiology of the baroreflex system and the neurohumoral changes that occur with standing are analyzed. Evidence is presented of the involvement of the autonomic nervous system, including studies of heart rate variability, microneurography, cardiac innervation, and molecular genetic studies. Finally, we describe different studies on the use of beta-blockers and norepinephrine transporter inhibitors (sibutramine, reboxetine) and the rationality of their use to prevent this type of syncope. Creative Commons

Relationship between size and latency of action potentials in human muscle sympathetic nerve activity.

PubMed

Salmanpour, Aryan; Brown, Lyndon J; Steinback, Craig D; Usselman, Charlotte W; Goswami, Ruma; Shoemaker, J Kevin

2011-06-01

We employed a novel action potential detection and classification technique to study the relationship between the recruitment of sympathetic action potentials (i.e., neurons) and the size of integrated sympathetic bursts in human muscle sympathetic nerve activity (MSNA). Multifiber postganglionic sympathetic nerve activity from the common fibular nerve was collected using microneurography in 10 healthy subjects at rest and during activation of sympathetic outflow using lower body negative pressure (LBNP). Burst occurrence increased with LBNP. Integrated burst strength (size) varied from 0.22 ± 0.07 V at rest to 0.28 ± 0.09 V during LBNP. Sympathetic burst size (i.e., peak height) was directly related to the number of action potentials within a sympathetic burst both at baseline (r = 0.75 ± 0.13; P < 0.001) and LBNP (r = 0.75 ± 0.12; P < 0.001). Also, the amplitude of detected action potentials within sympathetic bursts was directly related to the increased burst size at both baseline (r = 0.59 ± 0.16; P < 0.001) and LBNP (r = 0.61 ± 0.12; P < 0.001). In addition, the number of detected action potentials and the number of distinct action potential clusters within a given sympathetic burst were correlated at baseline (r = 0.7 ± 0.1; P < 0.001) and during LBNP (r = 0.74 ± 0.03; P < 0.001). Furthermore, action potential latency (i.e., an inverse index of neural conduction velocity) was decreased as a function of action potential size at baseline and LBNP. LBNP did not change the number of action potentials and unique clusters per sympathetic burst. It was concluded that there exists a hierarchical pattern of recruitment of additional faster conducting neurons of larger amplitude as the sympathetic bursts become stronger (i.e., larger amplitude bursts). This fundamental pattern was evident at rest and was not altered by the level of baroreceptor unloading applied in this study.

Mood states, sympathetic activity, and in vivo beta-adrenergic receptor function in a normal population.

PubMed

Yu, Bum-Hee; Kang, Eun-Ho; Ziegler, Michael G; Mills, Paul J; Dimsdale, Joel E

2008-01-01

The purpose of this study was to examine the relationship between mood states and beta-adrenergic receptor function in a normal population. We also examined if sympathetic nervous system activity is related to mood states or beta-adrenergic receptor function. Sixty-two participants aged 25-50 years were enrolled in this study. Mood states were assessed using the Profile of Mood States (POMS). Beta-adrenergic receptor function was determined using the chronotropic 25 dose isoproterenol infusion test. Level of sympathetic nervous system activity was estimated from 24-hr urine norepinephrine excretion. Higher tension-anxiety, depression-dejection, and anger-hostility were related to decreased beta-adrenergic receptor sensitivity (i.e., higher chronotropic 25 dose values), but tension-anxiety was the only remaining independent predictor of beta-adrenergic receptor function after controlling for age, gender, ethnicity, and body mass index (BMI). Urinary norepinephrine excretion was unrelated to either mood states or beta-adrenergic receptor function. These findings replicate previous reports that anxiety is related to decreased (i.e., desensitized) beta-adrenergic receptor sensitivity, even after controlling for age, gender, ethnicity, and body mass index.

Brain-Targeted (Pro)Renin Receptor Knockdown attenuates Angiotensin II-Dependent Hypertension

PubMed Central

Li, Wencheng; Peng, Hua; Cao, Theresa; Sato, Ryosuke; McDaniels, Sarah. J.; Kobori, Hiroyuki; Navar, L. Gabriel; Feng, Yumei

2012-01-01

The (pro)renin receptor is a newly discovered member of the brain renin-angiotensin system. To investigate the role of brain (pro)renin receptor in hypertension, adeno-associated virus-mediated (pro)renin receptor shRNA was used to knockdown (pro)renin receptor expression in the brain of non-transgenic normotensive and human renin-angiotensinogen double transgenic hypertensive mice. Blood pressure was monitored using implanted telemetric probes in conscious animals. Real-time PCR and immunostaining were performed to determine (pro)renin receptor, angiotensin II type 1 receptor and vasopressin mRNA levels. Plasma vasopressin levels were determined by Enzyme-Linked Immuno Sorbent Assay. Double transgenic mice exhibited higher blood pressure, elevated cardiac and vascular sympathetic tone, and impaired spontaneous baroreflex sensitivity. Intracerebroventricular delivery of (pro)renin receptor shRNA significantly reduced blood pressure, cardiac and vasomotor sympathetic tone, and improved baroreflex sensitivity compared to the control virus treatment in double transgenic mice. (Pro)renin receptor knockdown significantly reduced angiotensin II type 1 receptor and vasopressin levels in double transgenic mice. These data indicate that (pro)renin receptor knockdown in the brain attenuates angiotensin II-dependent hypertension and is associated with a decrease insympathetic tone and an improvement of the baroreflex sensitivity. In addition, brain-targeted (pro)renin receptor knockdown is associated with down-regulation of angiotensin II type 1 receptor and vasopressin levels. We conclude that central (pro)renin receptor contributes to the pathogenesis of hypertension in human renin-angiotensinogen transgenic mice. PMID:22526255

Behavioral, psycho-physiological and salivary cortisol modifications after short-term alprazolam treatment in patients with recent myocardial infarction.

PubMed

Pruneti, Carlo; Giusti, Mariarosa; Boem, Adriano; Luisi, Michele

2002-01-01

The aim of this study was to determine the behavioral and physiological effects of the central nervous system depressant alprazolam on a group of cardiac patients. Immediately after hospital discharge, the Crown and Crisp Experiential Index (CCEI) was administered, the salivary cortisol was detected and a psycho-physiological profile was recorded in 52 subjects who had suffered from myocardial infarction. Half of the subjects represented the experimental group and the remaining 26 individuals acted as a control group not undergoing treatment. The benzodiazepine alprazolam (0.25 mg) was administered twice daily to the treated group only. With the exception of the administration of the drug, all recruited subjects underwent the same clinical evaluation. The CCEI data of the treated group showed significant decreases for the following scales: free floating anxiety (p < 0.001), phobic anxiety (p < 0.01), somatic complaints (p < 0.05), and depression (p < 0.01). In the same group, with regard to the physiological parameters, the skin conductance response significantly decreased during the baseline phase (p < 0.01), and almost all parameters showed decreased values during mental stress test administration. Cortisol levels also decreased during the recovery phase of the psycho-physiological profile assessment. Alprazolam seems to be able to reduce sympathetic discharge and some stress-related behavioral and physiological responses. This could be of benefit for selected cardiac patients for whom increases in sympathetic tone may constitute a risk factor.

Sequential modulation of cardiac autonomic control induced by cardiopulmonary and arterial baroreflex mechanisms

NASA Technical Reports Server (NTRS)

Furlan, R.; Jacob, G.; Palazzolo, L.; Rimoldi, A.; Diedrich, A.; Harris, P. A.; Porta, A.; Malliani, A.; Mosqueda-Garcia, R.; Robertson, D.

2001-01-01

BACKGROUND: Nonhypotensive lower body negative pressure (LBNP) induces a reflex increase in forearm vascular resistance and muscle sympathetic neural discharge without affecting mean heart rate. We tested the hypothesis that a reflex change of the autonomic modulation of heartbeat might arise during low intensity LBNP without changes of mean heart rate. METHODS AND RESULTS: Ten healthy volunteers underwent plasma catecholamine evaluation and a continuous recording of ECG, finger blood pressure, respiratory activity, and central venous pressure (CVP) during increasing levels of LBNP up to -40 mm Hg. Spectrum and cross-spectrum analyses assessed the changes in the spontaneous variability of R-R interval, respiration, systolic arterial pressure (SAP), and CVP and in the gain (alpha(LF)) of arterial baroreflex control of heart rate. Baroreceptor sensitivity was also evaluated by the SAP/R-R spontaneous sequences technique. LBNP began decreasing significantly: CVP at -10, R-R interval at -20, SAP at -40, and the indexes alpha(LF) and baroreceptor sensitivity at -30 and -20 mm Hg, compared with baseline conditions. Plasma norepinephrine increased significantly at -20 mm Hg. The normalized low-frequency component of R-R variability (LF(R-R)) progressively increased and was significantly higher than in the control condition at -15 mm Hg. CONCLUSIONS: Nonhypotensive LBNP elicits a reflex increase of cardiac sympathetic modulation, as evaluated by LF(R-R), which precedes the changes in the hemodynamics and in the indexes of arterial baroreflex control.

Thoracic Epidural Anesthesia Reduces Right Ventricular Systolic Function With Maintained Ventricular-Pulmonary Coupling.

PubMed

Wink, Jeroen; de Wilde, Rob B P; Wouters, Patrick F; van Dorp, Eveline L A; Veering, Bernadette Th; Versteegh, Michel I M; Aarts, Leon P H J; Steendijk, Paul

2016-10-18

Blockade of cardiac sympathetic fibers by thoracic epidural anesthesia may affect right ventricular function and interfere with the coupling between right ventricular function and right ventricular afterload. Our main objectives were to study the effects of thoracic epidural anesthesia on right ventricular function and ventricular-pulmonary coupling. In 10 patients scheduled for lung resection, right ventricular function and its response to increased afterload, induced by temporary, unilateral clamping of the pulmonary artery, was tested before and after induction of thoracic epidural anesthesia using combined pressure-conductance catheters. Thoracic epidural anesthesia resulted in a significant decrease in right ventricular contractility (ΔESV 25 : +25.5 mL, P=0.0003; ΔEes: -0.025 mm Hg/mL, P=0.04). Stroke work, dP/dt MAX , and ejection fraction showed a similar decrease in systolic function (all P<0.05). A concomitant decrease in effective arterial elastance (ΔEa: -0.094 mm Hg/mL, P=0.004) yielded unchanged ventricular-pulmonary coupling. Cardiac output, systemic vascular resistance, and mean arterial blood pressure were unchanged. Clamping of the pulmonary artery significantly increased afterload (ΔEa: +0.226 mm Hg/mL, P<0.001). In response, right ventricular contractility increased (ΔESV 25 : -26.6 mL, P=0.0002; ΔEes: +0.034 mm Hg/mL, P=0.008), but ventricular-pulmonary coupling decreased (Δ(Ees/Ea) = -0.153, P<0.0001). None of the measured indices showed significant interactive effects, indicating that the effects of increased afterload were the same before and after thoracic epidural anesthesia. Thoracic epidural anesthesia impairs right ventricular contractility but does not inhibit the native positive inotropic response of the right ventricle to increased afterload. Right ventricular-pulmonary arterial coupling was decreased with increased afterload but not affected by the induction of thoracic epidural anesthesia. URL: http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=2844. Unique identifier: NTR2844. © 2016 American Heart Association, Inc.

Functional significance of the pattern of renal sympathetic nerve activation.

PubMed

Dibona, G F; Sawin, L L

1999-08-01

To assess the renal functional significance of the pattern of renal sympathetic nerve activation, computer-generated stimulus patterns (delivered at constant integrated voltage) were applied to the decentralized renal sympathetic nerve bundle and renal hemodynamic and excretory responses determined in anesthetized rats. When delivered at the same integrated voltage, stimulus patterns resembling those observed in in vivo multifiber recordings of renal sympathetic nerve activity (diamond-wave patterns) produced greater renal vasoconstrictor responses than conventional square-wave patterns. Within diamond-wave patterns, increasing integrated voltage by increasing amplitude produced twofold greater renal vasoconstrictor responses than by increasing duration. With similar integrated voltages that were subthreshold for renal vasoconstriction, neither diamond- nor square-wave pattern altered glomerular filtration rate, whereas diamond- but not square-wave pattern reversibly decreased urinary sodium excretion by 25 +/- 3%. At the same number of pulses per second, intermittent stimulation produced faster and greater renal vasoconstriction than continuous stimulation. At the same number of pulses per second, increases in rest period during intermittent stimulation proportionally augmented the renal vasoconstrictor response compared with that observed with continuous stimulation; the maximum augmentation of 55% occurred at a rest period of 500 ms. These results indicate that the pattern of renal sympathetic nerve stimulation (activity) significantly influences the rapidity, magnitude, and selectivity of the renal vascular and tubular responses.

Effects of renal sympathetic denervation on heart rate and atrioventricular conduction in patients with resistant hypertension.

PubMed

Ukena, Christian; Mahfoud, Felix; Spies, Aline; Kindermann, Ingrid; Linz, Dominik; Cremers, Bodo; Laufs, Ulrich; Neuberger, Hans-Ruprecht; Böhm, Michael

2013-09-10

Renal sympathetic denervation (RDN) reduces sympathetic activity and blood pressure (BP) in patients with resistant hypertension. The present study aimed to investigate the effects of RDN on HR and other electrocardiographic parameters. 136 patients aged 62.2 ± 0.8 years (58% male, BP 177 ± 2/93 ± 1 mmHg) with resistant hypertension underwent RDN. BP and a 12-lead electrocardiogram (ECG) were recorded before, 3 months (n=127), and 6 months (n=88) after RDN. After 3 months (3M) and 6 months (6M), systolic BP was reduced by 25.5 ± 2.4 mmHg (p<0.0001) and 28.1 ± 3 mmHg (p<0.0001). HR at baseline was 66.1 ± 1 beats per minute (bpm) and was reduced by 2.6 ± 0.8 bpm after 3 months (p=0.001) and 2.1 ± 1.1 bpm after 6 months (p=0.046). Patients with HR at baseline between 60-71 bpm and ≥ 71 bpm had a reduction of 2.9 ± 7.6 bpm (p=0.008) and 9.0 ± 8.6 bpm (p<0.0001), respectively, whereas in patients with baseline HR<60 bpm HR slightly increased after 3 months (2.7 ± 8.4 bpm; p=0.035). Neither baseline HR nor change of HR correlated with the reduction of systolic BP. The PR interval was prolonged by 11.3 ± 2.5 ms (p<0.0001) and 10.3 ± 2.5 ms (p<0.0001) at 3 and 6 months after RDN, respectively. Renal sympathetic denervation reduced heart rate and the PR interval as indicators of cardiac autonomic activity. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

The chronic infusion of hexamethonium and phenylephrine to effectively clamp sympathetic vasomotor tone. A novel approach.

PubMed

Collister, J P; Osborn, J W

1999-11-01

There are several ways to assess the sympathetic nervous system (i.e. , nerve recording, sympathectomy, etc.), each of which has its own limitations. The present study was conducted to establish a standard, testable chronic ganglionic blockade protocol with a fixed level of adrenergic vasomotor tone. Rats were instrumented with radio telemetry pressure transducers and venous catheters for continuous measurement of arterial pressure and infusion of pharmacologic agents, respectively. After 3 days of control measurements, rats were infused for 9 days with a continuous dose of the ganglionic blocking agent, hexamethonium and the alpha-adrenergic agonist, phenylephrine. In this way, sympathetic tone was effectively "clamped," which maintained a normal level of arterial pressure. Control pressure between hexamethonium + phenylephrine (HEX + PE) treated rats (101+/-2 mm Hg) and saline (VEHICLE) treated rats (101+/-2 mmHg) was not different. By day 9 of the infusion, there was no difference in arterial pressure between groups (VEHICLE: 101+/-3 mm Hg, HEX + PE: 103+/-3 mm Hg) or from the control period, although heart rate was significantly less in HEX + PE rats (VEHICLE: 406+/-9 beats/min vs. HEX + PE: 343+/-6 beats/min). The effectiveness of this technique was validated by measuring cardiac baroreceptor reflex sensitivity, as well as the pressor response to the direct ganglionic stimulating agent, 1, 1-dimethyl-4-phenylpiperazinium iodide (DMPP). Compared to VEHICLE rats, HEX + PE rats showed no tachycardic response to depressor stimuli and an absence of a pressor response to DMPP. We conclude that this protocol is a useful technique to chronically, yet reversibly, block the sympathetic nervous system in experimental settings.

The role of α-adrenergic receptors in mediating beat-by-beat sympathetic vascular transduction in the forearm of resting man

PubMed Central

Fairfax, Seth T; Holwerda, Seth W; Credeur, Daniel P; Zuidema, Mozow Y; Medley, John H; Dyke II, Peter C; Wray, D Walter; Davis, Michael J; Fadel, Paul J

2013-01-01

Sympathetic vascular transduction is commonly understood to act as a basic relay mechanism, but under basal conditions, competing dilatory signals may interact with and alter the ability of sympathetic activity to decrease vascular conductance. Thus, we determined the extent to which spontaneous bursts of muscle sympathetic nerve activity (MSNA) mediate decreases in forearm vascular conductance (FVC) and the contribution of local α-adrenergic receptor-mediated pathways to the observed FVC responses. In 19 young men, MSNA (microneurography), arterial blood pressure and brachial artery blood flow (duplex Doppler ultrasound) were continuously measured during supine rest. These measures were also recorded in seven men during intra-arterial infusions of normal saline, phentolamine (PHEN) and PHEN with angiotensin II (PHEN+ANG). The latter was used to control for increases in resting blood flow with α-adrenergic blockade. Spike-triggered averaging was used to characterize beat-by-beat changes in FVC for 15 cardiac cycles following each MSNA burst and a peak response was calculated. Following MSNA bursts, FVC initially increased by +3.3 ± 0.3% (P= 0.016) and then robustly decreased to a nadir of −5.8 ± 1.6% (P < 0.001). The magnitude of vasoconstriction appeared graded with the number of consecutive MSNA bursts; while individual burst size only had a mild influence. Neither PHEN nor PHEN+ANG infusions affected the initial rise in FVC, but both infusions significantly attenuated the subsequent decrease in FVC (–2.1 ± 0.7% and –0.7 ± 0.8%, respectively; P < 0.001 vs. normal saline). These findings indicate that spontaneous MSNA bursts evoke robust beat-by-beat decreases in FVC that are exclusively mediated via α-adrenergic receptors. PMID:23652594

Levels of craving influence psychological challenge and physiological reactivity.

PubMed

Frings, Daniel; Eskisan, Guleser; Spada, Marcantonio M; Albery, Ian P

2015-01-01

Behavioural and cognitive pathways that lead to the activation and escalation of craving have been studied extensively. Conversely, limited efforts have been directed towards understanding how craving relates to motivational systems and neuroendocrine responses. These can be understood using the biopsychosocial model of challenge and threat. In the current study, forty participants with varying levels of chocolate craving undertook two word searches, with the prospect of winning a piece of chocolate. Amongst those with high levels of craving, participation in this task led to motivational states of challenge relative to those with lower levels. This was reflected by changes in cardiac reactivity driven by differences in sympathetic-adrenal-medullar and hypothalamic-pituitary-adrenal axis activation. This finding suggests that craving can be associated with states of motivational challenge and thus affect cardiac reactivity. Copyright © 2014 Elsevier Ltd. All rights reserved.

Role of angiotensin in renal sympathetic activation in cirrhotic rats.

PubMed

Voigt, M D; Jones, S Y; DiBona, G F

1999-08-01

Central nervous system (CNS) renin-angiotensin activity influences the basal level of renal sympathetic nerve activity (RSNA) and its reflex regulation. The effect of type 1 angiotensin II (ANG II)-receptor antagonist treatment (losartan) on cardiac baroreflex regulation of RSNA and renal sodium handling was examined in rats with cirrhosis due to common bile duct ligation (CBDL). Basal levels of heart rate, mean arterial pressure (MAP), RSNA, and urinary sodium excretion were not affected by intracerebroventricular administration of either losartan or vehicle to CBDL rats. After acute intravenous isotonic saline loading (10% body wt) in vehicle-treated CBDL rats, MAP was unchanged and the decrease in RSNA seen in normal rats did not occur. However, in losartan-treated CBDL rats, there were significant concurrent but transient decreases in MAP (-20 +/- 2 mmHg) and RSNA (-25 +/- 3%). The natriuretic response to acute volume loading in losartan-treated CBDL rats was significantly less than that in vehicle-treated CBDL rats only at those time points where there were significant decreases in MAP. Antagonism of CNS ANG II type 1 receptors augments the renal sympathoinhibitory response to acute volume loading in CBDL. However, the natriuretic response to the acute volume loading is not improved, likely due to the strong antinatriuretic influence of the concomitant marked decrease in MAP (renal perfusion pressure) mediated by widespread sympathetic withdrawal from the systemic vasculature.

Cardiac Autonomic Responses during Exercise and Post-exercise Recovery Using Heart Rate Variability and Systolic Time Intervals-A Review.

PubMed

Michael, Scott; Graham, Kenneth S; Davis, Glen M

2017-01-01

Cardiac parasympathetic activity may be non-invasively investigated using heart rate variability (HRV), although HRV is not widely accepted to reflect sympathetic activity. Instead, cardiac sympathetic activity may be investigated using systolic time intervals (STI), such as the pre-ejection period. Although these autonomic indices are typically measured during rest, the "reactivity hypothesis" suggests that investigating responses to a stressor (e.g., exercise) may be a valuable monitoring approach in clinical and high-performance settings. However, when interpreting these indices it is important to consider how the exercise dose itself (i.e., intensity, duration, and modality) may influence the response. Therefore, the purpose of this investigation was to review the literature regarding how the exercise dosage influences these autonomic indices during exercise and acute post-exercise recovery. There are substantial methodological variations throughout the literature regarding HRV responses to exercise, in terms of exercise protocols and HRV analysis techniques. Exercise intensity is the primary factor influencing HRV, with a greater intensity eliciting a lower HRV during exercise up to moderate-high intensity, with minimal change observed as intensity is increased further. Post-exercise, a greater preceding intensity is associated with a slower HRV recovery, although the dose-response remains unclear. A longer exercise duration has been reported to elicit a lower HRV only during low-moderate intensity and when accompanied by cardiovascular drift, while a small number of studies have reported conflicting results regarding whether a longer duration delays HRV recovery. "Modality" has been defined multiple ways, with limited evidence suggesting exercise of a greater muscle mass and/or energy expenditure may delay HRV recovery. STI responses during exercise and recovery have seldom been reported, although limited data suggests that intensity is a key determining factor. Concurrent monitoring of HRV and STI may be a valuable non-invasive approach to investigate autonomic stress reactivity; however, this integrative approach has not yet been applied with regards to exercise stressors.

Cardiac Autonomic Responses during Exercise and Post-exercise Recovery Using Heart Rate Variability and Systolic Time Intervals—A Review

PubMed Central

Michael, Scott; Graham, Kenneth S.; Davis, Glen M.

2017-01-01

Cardiac parasympathetic activity may be non-invasively investigated using heart rate variability (HRV), although HRV is not widely accepted to reflect sympathetic activity. Instead, cardiac sympathetic activity may be investigated using systolic time intervals (STI), such as the pre-ejection period. Although these autonomic indices are typically measured during rest, the “reactivity hypothesis” suggests that investigating responses to a stressor (e.g., exercise) may be a valuable monitoring approach in clinical and high-performance settings. However, when interpreting these indices it is important to consider how the exercise dose itself (i.e., intensity, duration, and modality) may influence the response. Therefore, the purpose of this investigation was to review the literature regarding how the exercise dosage influences these autonomic indices during exercise and acute post-exercise recovery. There are substantial methodological variations throughout the literature regarding HRV responses to exercise, in terms of exercise protocols and HRV analysis techniques. Exercise intensity is the primary factor influencing HRV, with a greater intensity eliciting a lower HRV during exercise up to moderate-high intensity, with minimal change observed as intensity is increased further. Post-exercise, a greater preceding intensity is associated with a slower HRV recovery, although the dose-response remains unclear. A longer exercise duration has been reported to elicit a lower HRV only during low-moderate intensity and when accompanied by cardiovascular drift, while a small number of studies have reported conflicting results regarding whether a longer duration delays HRV recovery. “Modality” has been defined multiple ways, with limited evidence suggesting exercise of a greater muscle mass and/or energy expenditure may delay HRV recovery. STI responses during exercise and recovery have seldom been reported, although limited data suggests that intensity is a key determining factor. Concurrent monitoring of HRV and STI may be a valuable non-invasive approach to investigate autonomic stress reactivity; however, this integrative approach has not yet been applied with regards to exercise stressors. PMID:28611675

Renal sympathetic denervation increases renal blood volume per cardiac cycle: a serial magnetic resonance imaging study in resistant hypertension.

PubMed

Delacroix, Sinny; Chokka, Ramesh G; Nelson, Adam J; Wong, Dennis T; Sidharta, Samuel; Pederson, Stephen M; Rajwani, Adil; Nimmo, Joanne; Teo, Karen S; Worthley, Stephen G

2017-01-01

Preclinical studies have demonstrated improvements in renal blood flow after renal sympathetic denervation (RSDN); however, such effects are yet to be confirmed in patients with resistant hypertension. Herein, we assessed the effects of RSDN on renal artery blood flow and diameter at multiple time points post-RSDN. Patients (n=11) with systolic blood pressures ≥160 mmHg despite taking three or more antihypertensive medications at maximum tolerated dose were recruited into this single-center, prospective, non-blinded study. Magnetic resonance imaging indices included renal blood flow and renal artery diameters at baseline, 1 month and 6 months. In addition to significant decreases in blood pressures ( p <0.0001), total volume of blood flow per cardiac cycle increased by 20% from 6.9±2 mL at baseline to 8.4±2 mL ( p =0.003) at 1 month and to 8.0±2 mL ( p =0.04) 6 months post-procedure, with no changes in the renal blood flow. There was a significant decrease in renal artery diameters from 7±2 mm at baseline to 6±1 mm ( p =0.03) at 1 month post-procedure. This decrease was associated with increases in maximum velocity of blood flow from 73±20 cm/s at baseline to 78±19 cm/s at 1 month post-procedure. Notably, both parameters reverted to 7±2 mm and 72±18 cm/s, respectively, 6 months after procedure. RSDN improves renal physiology as evidenced by significant improvements in total volume of blood flow per cardiac cycle. Additionally, for the first time, we identified a transient decrease in renal artery diameters immediately after procedure potentially caused by edema and inflammation that reverted to baseline values 6 months post-procedure.