Autonomic Neuroscience-Basic & Clinical最新文献

To identify autonomic neuropathy (AN) phenotypes, we used principal component analysis on data from participants (N = 209) who underwent standardized autonomic testing including quantitative sudomotor axon reflex testing, and heart rate and blood pressure at rest and during tilt, Valsalva, and standardized deep breathing. The analysis identified seven clusters: 1) normal, 2) hyperadrenergic features without AN, 3) mild AN with hyperadrenergic features, 4) moderate AN, 5) mild AN with hypoadrenergic features, 6) borderline AN with hypoadrenergic features, 7) mild balanced deficits across parasympathetic, sympathetic and sudomotor domains. These findings demonstrate a complex relationship between adrenergic and other aspects of autonomic function.

Introduction

ICU patients with SARS-CoV-2-related pneumonia are at risk to develop a central dysautonomia which can contribute to mortality and respiratory failure. The pupillary size and its reactivity to light are controlled by the autonomic nervous system. Pupillometry parameters (PP) allow to predict outcomes in various acute brain injuries. We aim at assessing the most predictive PP of in-hospital mortality and the need for invasive mechanical ventilation (IV).

Material and methods

We led a prospective, two centers, observational study. We recruited adult patients admitted to ICU for a severe SARS-CoV-2 related pneumonia between April and August 2020. The pupillometry was performed at admission including the measurement of baseline pupillary diameter (PD), PD variations (PDV), pupillary constriction velocity (PCV) and latency (PDL).

Results

Fifty patients, 90 % males, aged 66 (60–70) years were included. Seven (14 %) patients died in hospital. The baseline PD (4.1 mm [3.5; 4.8] vs 2.6 mm [2.4; 4.0], P = 0.009), PDV (33 % [27; 39] vs 25 % [15; 36], P = 0.03) and PCV (3.5 mm.s⁻¹ [2.8; 4.4] vs 2.0 mm.s⁻¹ [1.9; 3.8], P = 0.02) were significantly lower in patients who will die. A PD value <2.75 mm was the most predictive parameter of in-hospital mortality, with an AUC = 0.81, CI 95 % [0.63; 0.99]. Twenty-four (48 %) patients required IV. PD and PDV were significantly lower in patients who were intubated (3.5 mm [2.8; 4.4] vs 4.2 mm [3.9; 5.2], P = 0.03; 28 % [25; 36 %] vs 35 % [32; 40], P = 0.049, respectively).

Conclusions

A reduced baseline PD is associated with bad outcomes in COVID-19 patients admitted in ICU. It is likely to reflect a brainstem autonomic dysfunction.

Nausea is a common clinical symptom, poorly managed with anti-emetic drugs. To identify potential brain regions which may be therapeutic targets we systematically reviewed brain imaging in subjects reporting nausea. The systematic review followed PRISMA statements with methodological quality (MINORS) and risk of bias (ROBINS-I) assessed. Irrespective of the nauseagenic stimulus the common (but not only) cortical structures activated were the inferior frontal gyrus (IFG), the anterior cingulate cortex (ACC) and the anterior insula (AIns) with some evidence for lateralization (Left-IFG, Right-AIns, Right-ACC). Basal ganglia structures (e.g., putamen) were also consistently activated. Inactivation was rarely reported but occurred mainly in the cerebellum and occipital lobe. During nausea, functional connectivity increased, mainly between the posterior and mid- cingulate cortex. Limitations include, a paucity of studies and stimuli, subject demographics, inconsistent definition and measurement of nausea. Structures implicated in nausea are discussed in the context of knowledge of central pathways for interoception, emotion and autonomic control. Comparisons are made between nausea and other aversive sensations as multimodal aversive conscious experiences.

Brown adipose tissue (BAT) contributes to energy homeostasis via nonshivering thermogenesis. The BAT is densely innervated by the sympathetic nervous system (SNS) and activity of pre-autonomic neurons modulates the sympathetic outflow. Leptin, an adipocyte hormone, alters energy homeostasis and thermogenesis of BAT via several neuronal circuits; however, the cellular effects of leptin on interscapular BAT (iBAT)-related neurons in the hypothalamus remain to be determined. In this study, we used pseudorabies virus (PRV) to identify iBAT-related neurons in the paraventricular nucleus (PVN) of the hypothalamus and test the hypothesis that iBAT-related PVN neurons are modulated by leptin. Inoculation of iBAT with PRV in leptin receptor reporter mice (Lepr:EGFP) demonstrated that a population of iBAT-related PVN neurons expresses Lepr receptors. Our electrophysiological findings revealed that leptin application caused hyperpolarization in some of iBAT-related PVN neurons. Bath application of leptin also modulated excitatory and inhibitory neurotransmission to most of iBAT-related PVN neurons. Using channel rhodopsin assisted circuit mapping we found that GABAergic and glutamatergic Lepr-expressing neurons in the dorsomedial hypothalamus/dorsal hypothalamic area (dDMH/DHA) project to PVN neurons; however, connected iBAT-related PVN neurons receive exclusively inhibitory signals from Lepr-expressing dDMH/DHA neurons.

Background

Hypertension is a widespread disease that, if persistent, increases the risks of coronary heart disease mortality and morbidity. Slow breathing is a recommended blood pressure-lowering strategy though the mechanisms mediating its effects are unknown.

Objective

This review aims to evaluate autonomic and vascular function as potential mediators driving BP adaptive responses with slow breathing.

Methods

We searched EBSCO host, Web of Science, Cochrane Central Register of Controlled Trials, and PubMed using key words for optimized search results.

Results

Nineteen studies were included in this review (11 device-guided; 8 non-device-guided breathing). Though some studies showed increased vagally mediated components of heart rate variability during slow breathing, results from acute and long-term studies were incongruent. Increases in baroreflex sensitivity (BRS) following a single device-guided slow breathing bout were noted in normotensive and hypertensive adults. Long-term (4 weeks to 3 months) effects of slow breathing on BRS were absent. Device-guided breathing resulted in immediate reductions in muscle sympathetic nerve activity (MSNA) in normo- and hyper-tensive adults though results from long-term studies yielded inconsistent findings. Non-device-guided slow breathing posed acute and chronic effects on vascular function with reductions in arterial stiffness in adults with type I diabetes and increases in microvascular endothelial function in adults with irritable bowel syndrome. Non-device guided breathing also reduced pro-inflammatory cytokines in healthy and hypertensive adults in acute and chronic studies. No adverse effects or non-adherence to treatment were noted in these trials.

Conclusion

Device-guided slow breathing is a feasible and effective modality in improving BRS, HRV, and arterial stiffness though its long-term effects are obscure. Though less evidence exists supporting the efficacy of non-device-guided slow breathing, acute and chronic studies demonstrate improvements in vascular function and inflammatory cytokines. More studies are needed to further explore the long-term effects of slow breathing in general and non-device-guided breathing in particular.

The immunohistochemical localization of proteins for synaptic release was examined in smooth muscle-associated sensory nerve endings using whole-mount preparations of the rat trachea. Plant-like smooth muscle-associated nerve endings with immunoreactivity for Na⁺-K⁺-ATPase, α₃-subunit were identified in the trachealis muscle. VGLUT1, synapsin1, t-SNARE proteins (SNAP25 and syntaxin1), v-SNARE proteins (VAMP1 and VAMP2), and a presynaptic active zone-related protein (piccolo) were detected in the terminal parts of these endings. These results suggest that smooth muscle-associated nerve endings secrete glutamate to modulate sensorimotor functions in the lung deflation reflex.

Purpose

To determine if the menstrual cycle and oral contraceptives (OC) influence responses to acute orthostatic stress and if these factors are clinically relevant to the diagnosis of initial orthostatic hypotension (iOH).

Methods

Young, healthy women were recruited, including OC users (n = 12) and non-users (NOC; n = 9). Women were tested during the low hormone (LH; placebo pills; days 2–5 natural cycle) and high hormone (HH; active dose; days 18–24 natural cycle) menstrual phases. Changes in mean arterial pressure, cardiac output, heart rate, the 30:15 heart rate ratio and cerebrovascular resistance indices within 30 s of standing were examined.

Results

There were no effects of OC or menstrual cycle on hemodynamic responses during standing (all p>0.05). In the LH phase, OC users had a greater fall in mean middle cerebral artery blood velocity (MCA_V) compared to NOC (p<0.05). However, this was reversed in the HH phase, where OC users had a reduced fall in mean MCA_V (p<0.05). Interestingly, 8 women (OC and NOC) had drops in systolic/diastolic blood pressure meeting the criteria for iOH, and 7 of those 8 women displayed this drop in a single phase of the menstrual cycle.

Conclusion

Our results indicate that chronic versus acute OC use (i.e., long-term use observed via LH phase versus short-term use observed via HH phase) have opposing effects on cerebral blood velocity during standing. Further, our results highlight that multiple assessments across the cycle may be necessary to accurately diagnose iOH, as most women met the diagnostic criteria during a single menstrual phase.

Background

Heart rate variability (HRV) may provide an estimation of the autonomous nervous system (ANS) integrity in critically ill patients. Disturbances of cerebral autoregulation (CAR) may share common pathways of ANS dysfunction.

Aim

To explore whether changes in HRV and CAR index correlate in critically ill septic patients.

Methods

Prospectively collected data on septic adult (> 18 years) patients admitted into a mixed Intensive Care between February 2016 and August 2019 with a recorded transcranial doppler CAR assessment. CAR was assessed calculating the Pearson's correlation coefficient (i.e. mean flow index, Mxa) between the left middle cerebral artery flow velocity (FV), insonated with a 2-MHz probe, and invasive blood pressure (BP) signal, both recorded simultaneously through a Doppler Box (DWL, Germany). MATLAB software was used for CAR assessment using a validated script; a Mxa >0.3 was considered as impaired CAR. HRV was assessed during the same time period using a specific software (Kubios HRV 3.2.0) and analyzed in both time-domain and frequency domain methods. Correlation between HRV-derived variables and Mxa were assessed using the Spearman's coefficient.

Results

A total of 141 septic patients was studied; median Mxa was 0.35 [0.13–0.60], with 77 (54.6 %) patients having an impaired CAR. Mxa had a significant although weak correlation with HRV time domain (SDNN, r = 0.17, p = 0.04; RMSSD, r = 0.18, p = 0.03; NN50, r = 0.23, p = 0.006; pNN50, r = 0.23, p = 0.007), frequency domain (FFT-HF, r = 0.21; p = 0.01; AR-HF, r = 0.19; p = 0.02), and non-linear domain (SD1, r = 0.18, p = 0.03) parameters. Impaired CAR patients had also all of these HRV-derived parameters higher than those with intact CAR.

Conclusions

In this exploratory study, a potential association of ANS dysfunction and impaired CAR during sepsis was observed.

Background and objective

Postural Orthostatic Tachycardia Syndrome (POTS) is a chronic health condition affecting mostly women of childbearing age, and significantly impacting their health and quality of life. It is currently poorly understood with no approved licensed treatments. The aim of this systematic review was to contextualize the symptom burden of POTS, and review factors associated with this burden that may guide future treatments. The specific questions were (1) How does symptom burden in POTS compare to the burden in other long term conditions (LTCs), (2) Which factors are associated with POTS symptom burden, and (3) Which interventions show promise in reducing symptom burden in POTS.

Databases and data treatment

Electronic databases (CENTRAL, MEDLINE, EMBASE, CINAHL, PsycINFO, Web of Science, APA PsycArticles, OpenGrey) were searched from inception to January 2022 for observational studies reporting on the association between any biological, psychological or social factors and symptom burden, and randomized controlled trials reporting on interventions for symptom burden in adults with POTS. Two reviewers independently conducted eligibility screening, data extraction and quality assessment. A narrative synthesis was undertaken.

Results/Conclusion

5159 entries were screened for eligibility. Twenty-nine studies were included (1372 participants with POTS of a total sample size of 2314, 17 High-, 12 Medium-quality), seventeen were observational and twelve were randomized controlled experimental and intervention trials. Overall methodological quality of the evidence was medium-high but heterogeneity was high and sample sizes modest, allowing moderately robust conclusions. Orthostatic symptom burden was higher in POTS than other LTCs. Serum activity against adrenergic α1 receptors, physical functioning, depression, catastrophizing, prolonged cognitive stress testing and anxiety were significantly associated with symptom burden in medium-high quality studies. Preliminary medium-high quality evidence from predominantly proof-of-concept (n = 11) studies and one 3-month 2 × 2 factorial design trial suggest that compression garments, propranolol, pyridostigmine, desmopressin, and bisoprolol may hold promise in reducing symptom burden. Directions for future research include investigating associated factors over time, the development of complex interventions which address both biological and psychosocial factors associated with symptom burden, and effectiveness trials of these interventions.

Significance

POTS symptom burden is high, particularly in relation to orthostatic intolerance when compared to other long-term conditions (LTCs). Despite this burden, there are no effectiveness randomized controlled trials of treatment to reduce symptoms in POTS. This review provides a starting point to understanding researched biological and psychosocial factor