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International Journal of Cardiology Oct 2019Insular cortex (IC) ischemic strokes are associated with increased risk of cardiac arrhythmias. We have previously hypothesized that the anatomical substrate for...
BACKGROUND
Insular cortex (IC) ischemic strokes are associated with increased risk of cardiac arrhythmias. We have previously hypothesized that the anatomical substrate for post-stroke neurogenic arrhythmias comprises stroke-induced left atrium (LA) coronary microvascular endothelial dysfunction (CMED), and myocardial inflammatory infiltration (MII) leading to myocardial fibrosis. We investigated whether selectively induced IC ischemic stroke in rats results in histopathological changes in the LA.
METHODS
Insular ischemic stroke was induced in 6-month old male Wistar rats via unilateral stereotaxic injection of endothelin-1 into the left or right IC. The control group consisted of rats injected with saline. We histologically examined the LA 28 days after stroke for CMED, MII, and fibrosis. We performed linear regression analyses to assess correlation between the 3 histopathological outcomes. We compared these findings in the distal LA and the LA-pulmonary vein border (LA-PV border), a region of rich autonomic innervation.
RESULTS
Right and left IC stroke led to CMED, MII, and fibrosis in the LA. MII was significantly correlated with CMED and fibrosis. The LA-PV border had significantly greater MII and fibrosis than the distal LA. There were no differences in coronary microvascular and myocardial changes between left and right IC strokes.
CONCLUSIONS
Left and right insular ischemic strokes resulted in CMED, MII, and fibrosis, the pathological hallmark of arrhythmogenic LA tissue. Since these changes were greater within the LA-PV border than in the distal LA tissue, the role of preganglionic fibers at the ganglionated plexi as part of neurogenic arrhythmogenesis warrants further investigation.
Topics: Animals; Atrial Function, Left; Brain Ischemia; Cerebral Cortex; Endothelium, Vascular; Fibrosis; Male; Microvessels; Myocarditis; Myocardium; Rats; Rats, Wistar; Stroke
PubMed: 31196685
DOI: 10.1016/j.ijcard.2019.06.004 -
Frontiers in Physiology 2018Nitric oxide (NO) is a diffusible gas and has multifarious effects on both pre- and postsynaptic events. As a consequence of complex excitatory and inhibitory...
Nitric oxide (NO) is a diffusible gas and has multifarious effects on both pre- and postsynaptic events. As a consequence of complex excitatory and inhibitory integrations, NO effects on neuronal activities are heterogeneous. Using preparations of neonatal rats that retain the splanchnic sympathetic nerves and the thoracic spinal cord as an experimental model, we report here that either enhancement or attenuation of NO production in the neonatal rat spinal cords could increase, decrease, or not change the spontaneous firing behaviors recorded from splanchnic sympathetic single fibers. To elucidate the mathematical features of NO-mediated heterogeneous responses, the ratios of changes in firing were plotted against their original firing rates. In log-log plots, a linear data distribution demonstrated that NO-mediated heterogeneity in sympathetic firing responses was well described by a power function. Selective antagonists were applied to test if glycinergic, GABAergic, glutamatergic, and cholinergic neurotransmission in the spinal cord are involved in NO-mediated power-law firing modulations (plFM). NO-mediated plFM diminished in the presence of mecamylamine (an open-channel blocker of nicotinic cholinergic receptors), indicating that endogenous nicotinic receptor activities were essential for plFM. Applications of strychnine (a glycine receptor blocker), gabazine (a GABA receptor blocker), or kynurenate (a broad-spectrum ionotropic glutamate receptor blocker) also caused plFM. However, strychnine- or kynurenate-induced plFM was diminished by L-NAME (an NO synthase inhibitor) pretreatments, indicating that the involvements of glycine or ionotropic glutamate receptor activities in plFM were secondary to NO signaling. To recapitulate the arithmetic natures of the plFM, the plFM were simulated by firing changes in two components: a step increment and a fractional reduction of their basal firing activities. Ionotropic glutamate receptor activities were found to participate in plFM by both components. In contrast, GABA receptor activities are involved in the component of fractional reduction only. These findings suggest that NO orchestrates a repertoire of excitatory and inhibitory neurotransmissions, incurs a shunting effect on postsynaptic membrane properties, and thus, alters sympathetic firing in a manner of plFM. We propose that the plFM mediated by NO forms a basic scheme of differential controls for heterogeneous sympathetic regulation of visceral functions.
PubMed: 29559921
DOI: 10.3389/fphys.2018.00163 -
Veterinary Ophthalmology Jan 2015To investigate whether idiopathic Horner's syndrome (HS) in Golden Retrievers is an exclusively preganglionic disorder based on denervation hypersensitivity...
OBJECTIVE
To investigate whether idiopathic Horner's syndrome (HS) in Golden Retrievers is an exclusively preganglionic disorder based on denervation hypersensitivity pharmacological testing with phenylephrine.
ANIMALS STUDIED
Medical records of dogs presented with HS between 2000 and 2012. Dogs presented with additional ocular or systemic signs were excluded.
PROCEDURES
Clinical data examined included age, sex, duration of clinical signs, ancillary diagnostic test results, and time to mydriasis on topical ocular application of 1% phenylephrine. Lesions were diagnosed as postganglionic (mydriasis within 20 min) or preganglionic (mydriasis between 20 and 45 min).
RESULTS
Medical records of 21 dogs of nine different breeds were included. An etiopathogenesis for Horner's syndrome was determined in five dogs, none of which were Golden Retrievers. All diagnoses correlated with pharmacological lesion localization. Ten Golden Retrievers were included (eight male and two female) with a mean age of 8.5 years (range: 4-13). Lesion localization was diagnosed as postganglionic in eight (mean: 10 min [range: 6-18]) and preganglionic in two Golden Retrievers (20 and 24 min). All cases were unilateral and had completely resolved within 15 weeks (range: 11-20). Recurrence was not reported in any of the patients.
CONCLUSIONS
Idiopathic postganglionic HS was diagnosed in eight of 10 Golden Retrievers contradicting previous reports of a purely preganglionic localization. Etiopathogenesis of canine idiopathic HS remains to be determined; nevertheless, a vascular etiology cannot be excluded. Future studies using magnetic resonance angiography may aid in clarifying the pathogenesis.
Topics: Animals; Autonomic Fibers, Preganglionic; Blepharoptosis; Dog Diseases; Dogs; Female; Horner Syndrome; Male; Miosis; Phenylephrine; Species Specificity; Sympathetic Fibers, Postganglionic; Sympathomimetics
PubMed: 24028692
DOI: 10.1111/vop.12096 -
Eksperimental'naia I Klinicheskaia... 2016The study of mechanisms of regulation of biliary tract motility by divisions of autonomic nervous system (ANS).
AIM
The study of mechanisms of regulation of biliary tract motility by divisions of autonomic nervous system (ANS).
MATERIAL AND METHODS
Experiments were carried out on rabbits, chinchillas weighing 3.5-4 kg using gentle methods of treatment of experimental animals. Electromotor activity of electromotor (EMA) of the gallbladder and sphincter of Oddi was recorded. Irritation of the nerve produces an electrical pulse duration of 2 ms, the amplitude of 1.5-15 V, frequency of 10 Hz.
RESULTS
The mechanism of vagal inhibition of sphincter of Oddi motility and unidirectional stimulatory influence of ANS divisions on the motility of the gallbladder and sphincter of Oddi was studied. It was established that in the mechanism of vagal inhibition of sphincter of Oddi motility involved intramural adrenergic neurons synaptically connected with preganglionic parasympathetic fibers. At the stimulatory effect of vagus on biliary tract motility serotonergic intramural neurons are involved transmitting excitation to serotonin receptors of effector tissue.
Topics: Animals; Autonomic Nervous System; Electric Stimulation; Gallbladder; Gallbladder Emptying; Rabbits; Sphincter of Oddi
PubMed: 30284425
DOI: No ID Found -
Neuroscience Jul 2017Corticotropin-releasing hormone release is the final common pathway of stress-associated neuroendocrine responses. This study tested how corticotropin-releasing hormone...
Corticotropin-releasing hormone modulates airway vagal preganglionic neurons of Sprague-Dawley rats at multiple synaptic sites via activation of its type 1 receptors: Implications for stress-associated airway vagal excitation.
Corticotropin-releasing hormone release is the final common pathway of stress-associated neuroendocrine responses. This study tested how corticotropin-releasing hormone modulates airway vagal preganglionic neurons. Airway vagal preganglionic neurons in neonatal rats were retrogradely labeled with fluorescent dye and identified in medullary slices, and their responses to corticotropin-releasing hormone (200nmolL) were examined using whole-cell patch clamp. The results show that under current clamp, corticotropin-releasing hormone (200nmolL) depolarized airway vagal preganglionic neurons and significantly increased the rate of their spontaneous firing. Under voltage clamp, corticotropin-releasing hormone caused a tonic inward current and significantly facilitated the spontaneous glutamatergic and GABAergic inputs of these neurons. Corticotropin-releasing hormone had no impact on the spontaneous glycinergic inputs of these neurons. In the preexistence of tetrodotoxin (1μmolL), corticotropin-releasing hormone had no impact on the miniature excitatory or inhibitory postsynaptic currents, but still induced a tonic inward current and significantly increased the input resistance. The responses induced by corticotropin-releasing hormone were prevented by Antalarmin hydrochloride (50μmolL), an antagonist of type 1 corticotropin-releasing hormone receptors, but insensitive to Astressin 2B (200nmolL), an antagonist of type 2 corticotropin-releasing hormone receptors. These results suggest that corticotropin-releasing hormone excites airway vagal preganglionic neurons via activation of its type 1 receptors at multiple sites, which includes a direct postsynaptic excitatory action and presynaptic facilitation of both glutamatergic and GABAergic inputs. In stress, corticotropin-releasing hormone might be able to activate the airway vagal nerves and, consequently, participate in induction or exacerbation of airway disorders.
Topics: 6-Cyano-7-nitroquinoxaline-2,3-dione; Animals; Animals, Newborn; Autonomic Fibers, Preganglionic; Bicuculline; Corticotropin-Releasing Hormone; Excitatory Amino Acid Antagonists; Excitatory Postsynaptic Potentials; Female; GABA-A Receptor Antagonists; Male; Medulla Oblongata; Neurons; Peptide Fragments; Peptides, Cyclic; Pyrimidines; Pyrroles; Rats; Rats, Sprague-Dawley; Receptors, Corticotropin-Releasing Hormone; Sodium Channel Blockers; Synapses; Tetrodotoxin; Vagus Nerve
PubMed: 28499969
DOI: 10.1016/j.neuroscience.2017.04.049 -
JACC. Clinical Electrophysiology Sep 2017This study sought to examine the efficacy of low-level vagus nerve stimulation (LLVNS) in suppressing post-operative atrial fibrillation (POAF) and inflammatory... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVES
This study sought to examine the efficacy of low-level vagus nerve stimulation (LLVNS) in suppressing post-operative atrial fibrillation (POAF) and inflammatory cytokines in patients undergoing cardiac surgery.
BACKGROUND
POAF often complicates cardiac surgery.
METHODS
Patients undergoing cardiac surgery were randomized to active or sham LLVNS. In all patients, a bipolar wire was sutured to the vagus nerve pre-ganglionic fibers alongside the lateral aspect of the superior vena cava. High-frequency (20 Hz) stimulation, 50% below the threshold for slowing the heart rate, was delivered for 72 h in the LLVNS group. The development of POAF was monitored continuously during the entire hospital stay by use of telemetry. Blood was collected on arrival in the intensive care unit and at 24 and 72 h for measurement of inflammatory cytokines. Patients were followed up within 1 month after cardiac surgery.
RESULTS
A total of 54 patients were randomized to either active LLVNS (n = 26) or sham control (n = 28). The baseline characteristics of the patients were balanced in the 2 groups. POAF occurred in 3 patients (12%) in the LLVNS group and 10 patients (36%) in the control group (hazard ratio: 0.28; 95% confidence interval: 0.10 to 0.85; p = 0.027). None of the patients developed any complications as a result of wire placement. At 72 h, serum tumor necrosis factor-α and interleukin-6 levels were significantly lower in the LLVNS group than in the control group.
CONCLUSIONS
These data suggest that LLVNS suppresses POAF and attenuates inflammation in patients undergoing cardiac surgery. Further studies are warranted.
Topics: Adult; Aged; Atrial Fibrillation; Cytokines; Female; Humans; Inflammation; Interleukin-6; Male; Middle Aged; Postoperative Complications; Prospective Studies; Thoracic Surgery; Tumor Necrosis Factor-alpha; Vagus Nerve; Vagus Nerve Stimulation
PubMed: 29759717
DOI: 10.1016/j.jacep.2017.02.019 -
Journal of Neurophysiology Apr 2019Cholinergic vagal nerves projecting from neurons in the brain stem nucleus ambiguus (NAm) play a predominant role in cardiac parasympathetic pacemaking control. Central...
Cholinergic vagal nerves projecting from neurons in the brain stem nucleus ambiguus (NAm) play a predominant role in cardiac parasympathetic pacemaking control. Central adrenergic signaling modulates the tone of this vagal output; however, the exact excitability mechanisms are not fully understood. We investigated responses of NAm neurons to adrenergic agonists using in vitro mouse brain stem slices. Preganglionic NAm neurons were identified by ChAT-tdTomato fluorescence in young adult transgenic mice, and their cardiac projection was confirmed by retrograde dye tracing. Juxtacellular recordings detected sparse or absent spontaneous action potentials (AP) in NAm neurons. However, bath application of epinephrine or norepinephrine strongly and reversibly activated most NAm neurons regardless of their basal firing rate. Epinephrine was more potent than norepinephrine, and this activation largely depends on α-adrenoceptors. Interestingly, adrenergic activation of NAm neurons does not require an ionotropic synaptic mechanism, because postsynaptic excitatory or inhibitory receptor blockade did not occlude the excitatory effect, and bath-applied adrenergic agonists did not alter excitatory or inhibitory synaptic transmission. Instead, adrenergic agonists significantly elevated intrinsic membrane excitability to facilitate generation of recurrent action potentials. T-type calcium current and hyperpolarization-activated current are involved in this excitation pattern, although not required for spontaneous AP induction by epinephrine. In contrast, pharmacological blockade of persistent sodium current significantly inhibited the adrenergic effects. Our results demonstrate that central adrenergic signaling enhances the intrinsic excitability of NAm neurons and that persistent sodium current is required for this effect. This central balancing mechanism may counteract excessive peripheral cardiac excitation during increased sympathetic tone. NEW & NOTEWORTHY Cardiac preganglionic cholinergic neurons in the nucleus ambiguus (NAm) are responsible for slowing cardiac pacemaking. This study identified that adrenergic agonists can induce rhythmic action potentials in otherwise quiescent cholinergic NAm preganglionic neurons in brain stem slice preparation. The modulatory influence of adrenaline on central parasympathetic outflow may contribute to both physiological and deleterious cardiovascular regulation.
Topics: Action Potentials; Adrenergic Agonists; Animals; Autonomic Fibers, Preganglionic; Calcium Channels, T-Type; Epinephrine; Female; Heart; Male; Medulla Oblongata; Mice; Norepinephrine; Periodicity; Sodium Channels; Synaptic Potentials
PubMed: 30699052
DOI: 10.1152/jn.00761.2018 -
Frontiers in Neuroanatomy 2016Preganglionic parasympathetic neurons of the ventromedial part of the superior salivatory nucleus (SSN) mediate vasodilation of orbital and choroidal blood vessels, via...
Preganglionic parasympathetic neurons of the ventromedial part of the superior salivatory nucleus (SSN) mediate vasodilation of orbital and choroidal blood vessels, via their projection to the nitrergic pterygopalatine ganglion (PPG) neurons that innervate these vessels. We recently showed that the baroresponsive part of the nucleus of the solitary tract (NTS) innervates choroidal control parasympathetic preganglionic neurons of SSN in rats. As this projection provides a means by which blood pressure (BP) signals may modulate choroidal blood flow (ChBF), we investigated if activation of baroresponsive NTS evokes ChBF increases in rat eye, using Laser Doppler Flowmetry (LDF) to measure ChBF transclerally. We found that electrical activation of ipsilateral baroresponsive NTS and its efferent fiber pathway to choroidal SSN increased mean ChBF by about 40-80% above baseline, depending on current level. The ChBF responses obtained with stimulation of baroresponsive NTS were driven by increases in both choroidal blood volume (ChBVol; i.e., vasodilation) and choroidal blood velocity (ChBVel; possibly due to orbital vessel dilation). Stimulation of baroresponsive NTS, by contrast, yielded no significant mean increases in systemic arterial blood pressure (ABP). We further found that the increases in ChBF with NTS stimulation were significantly reduced by administration of the neuronal nitric oxide (NO) synthase inhibitor N-propyl-l-arginine (NPA), thus implicating nitrergic PPG terminals in the NTS-elicited ChBF increases. Our results show that the NTS neurons projecting to choroidal SSN do mediate increase in ChBF, and thus suggest a role of baroresponsive NTS in the BP-dependent regulation of ChBF.
PubMed: 27774055
DOI: 10.3389/fnana.2016.00094 -
Neurology Aug 2019
Topics: Autonomic Dysreflexia; Autonomic Fibers, Preganglionic; Humans; Interneurons; Male; Spinal Cord; Spinal Cord Injuries; Sympathetic Nervous System
PubMed: 31308152
DOI: 10.1212/WNL.0000000000007973 -
PloS One 2017In Mexico, although the majority of births are attended in hospitals, reports have emerged of obstetric violence, use of unsafe practices, and failure to employ... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
In Mexico, although the majority of births are attended in hospitals, reports have emerged of obstetric violence, use of unsafe practices, and failure to employ evidence-based practices (EBP). Recent attention has refocused global efforts towards provision of quality care that is both patient-centered and evidence-based. Scaling up of local interventions should rely on strong evidence of effectiveness.
OBJECTIVE
To perform a secondary analysis to evaluate the impact of a simulation and team-training program (PRONTO) on the performance of EBP in normal births.
METHODS
A pair-matched cluster randomized controlled trial of the intervention was designed to measure the impact of the program (PRONTO intervention) on a sample of 24 hospitals (12 hospitals received the PRONTO training and 12 served as controls) in the states of Chiapas, Guerrero, and Mexico. We estimated the impact of receiving the intervention on the probability of birth practices performance in a sample of 641 observed births of which 318 occurred in the treated hospitals and 323 occurred in control hospitals. Data was collected at 4 time points (baseline, 4th, 8th and 12th months after the training). Women were blinded to treatment allocation but observers and providers were not. Estimates were obtained by fitting difference-in-differences logistic regression models considering confounding variables. The trial is registered at clinicaltrials.gov: # NCT01477554.
RESULTS
Significant changes were found following the intervention. At 4 months post-intervention an increase of 20 percentage points (p.p.) for complete Active Management of Third Stage of Labor (AMTSL) (p = 0.044), and 16 p.p. increase for Skin-to-Skin Contact (p = 0.067); at 12 months a 25 p.p. increase of the 1st step of AMTSL (p = 0.026) and a 42 p.p. increase of Delayed Cord Clamping (p = 0.004); at 4 months a 30 (p = 0.001) and at 8 months a 22 (p = 0.010) p.p. decrease for Uterine Sweeping.
CONCLUSIONS
The intervention has an impact on adopting EBP at birth, contributing to an increased quality of care. Long lasting impacts on these practices are possible if there were to be a widespread adoption of the training techniques including simulation, team-training and facilitated discussions regarding routine care.
Topics: Autonomic Fibers, Preganglionic; Delivery, Obstetric; Emergency Medical Services; Evidence-Based Practice; Health Personnel; Hospitals; Humans; Intensive Care, Neonatal; Mexico; Patient Care Team; Quality Improvement
PubMed: 28319122
DOI: 10.1371/journal.pone.0172623