This study aimed to evaluate the feasibility of transcutaneous auricular vagal nerve stimulation (tAVNS) in healthy horses and its effect on heart rate variability (HRV). The study comprised three phases: the selection of mares, their acclimatization to the tAVNS, and the stimulation phase. Stimulation was performed with two electrodes positioned on the right pinna. The settings were 0.5 mA, 250 μs, and 25 Hz for pulse amplitude, pulse width, and pulse frequency, respectively. HRV was analysed before (B1), during (T), and after (B2) the tAVNS. From the 44 mares initially included, only 7 completed the three phases. In these mares, the heart rate (HR) was significantly lower, and frequency domain parameters showed an increased parasympathetic tone in B2 compared with B1. However, in 3/7 mares, the HR was significantly higher during T compared with B1 and B2, compatible with a decreased parasympathetic tone, while in 4/7 mares, the HR was significantly lower and the parasympathetic nervous system index was significantly higher during T and B2 compared with B1. The tAVNS is an economical and easy procedure to perform and has the potential to stimulate vagal activity; however, it was poorly tolerated in the mares included in this study.

BACKGROUND: Osteoarthritis (OA) is a chronic degenerative joint disease causing limited mobility and pain, with no curative treatment available. Recent in vivo studies suggested autonomic alterations during OA progression in patients, yet clinical evidence is scarce. Therefore, autonomic tone was analyzed in OA patients via heart rate variability (HRV) measurements.
METHODS: Time-domain (SDRR, RMSSD, pRR50) and frequency-domain (LF, HF, LF/HF) HRV indices were determined to quantify sympathetic and parasympathetic activities. In addition, perceived stress, WOMAC pain as well as serum catecholamines, cortisol and dehydroepiandrosterone-sulphate (DHEA-S) were analyzed. The impact of the grade of disease (GoD) was evaluated by linear regression analysis and correlations with clinical data were performed.
RESULTS: GoD significantly impacted the autonomic tone in OA patients. All time-domain parameters reflected slightly decreased HRV in early OA patients and significantly reduced HRV in late OA patients. Moreover, frequency-domain analysis revealed decreased HF and LF power in all OA patients, reflecting diminished parasympathetic and sympathetic activities. However, LF/HF ratio was significantly higher in early OA patients compared to late OA patients and implied a clear sympathetic dominance. Furthermore, OA patients perceived significantly higher chronic stress and WOMAC pain levels compared to healthy controls. Serum cortisol and cortisol/DHEA-S ratio significantly increased with GoD and positively correlated with WOMAC pain. In contrast, serum catecholamines only trended to increase with GoD and pain level.
CONCLUSIONS: This prospective study provides compelling evidence of an autonomic dysfunction with indirect sympathetic dominance in early and late knee OA patients for the first time based on HRV analyses and further confirmed by serum stress hormone measurements. Increased sympathetic activity and chronic low-grade inflammation in OA as well as in its major comorbidities reinforce each other and might therefore create a vicious cycle. The observed autonomic alterations coupled with increased stress and pain levels highlight the potential of HRV as a prognostic marker. In addition, modulation of autonomic activity represents an attractive future therapeutic option.

BACKGROUND: Autonomic nervous system (ANS) testing has aided in our ability to evaluate autonomic dysfunction in migraine patients. We reviewed the literature in multiple databases which investigate ANS function in migraine patients and healthy subjects.
METHODS: This systematic review and meta-analysis examined the respective deep breathing, Valsalva manoeuvre, orthostatic and isometric challenge results, using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and Meta-analyses of Observational Studies in Epidemiology (MOOSE) statements.
RESULTS: Seven articles met all inclusion criteria. Fixed-effects meta-analysis showed migraine patients (n = 424), collectively, had lower interictal autonomic test results compared with healthy controls (n = 268). In detail, this was true for the standardized mean difference (g) of deep breathing (g= -0.32; 95% confidence interval (CI) -0.48, -0.16), orthostatic challenge (g= -0.28; 95% CI -0.44, -0.13) and isometric challenge (g= -0.55; 95% CI -0.71, -0.39) and for the difference of means (MD) of the Valsalva ratio (MD = -0.17; 95% CI -0.23, -0.10).
CONCLUSIONS: Interictal ANS dysfunction can be identified in migraine patients when compared to healthy controls. These findings indicate the importance to evaluate ANS function in migraine patients - especially, as migraine-specific prophylactic therapies (such as anti-calcitonin gene-related peptide (CGRP) antibodies) may affect the function of the ANS.

OBJECTIVE: This study aimed to assess the course of changes in choroidal morphology after immersion of the foot in warm water at 40°C using enhanced depth imaging optical coherence tomography (EDI-OCT).
METHODS: Forty-three right eyes of 43 healthy participants were included. Changes in choroidal morphology were determined using EDI-OCT to evaluate subfoveal choroidal thickness (SCT). Systolic, diastolic, and mean blood pressures (SBP, DBP, and MBP, respectively) were also measured to determine systemic circulatory dynamics at baseline, immediately after immersion (0 min), and 10, 20, and 30 min after immersion.
RESULTS: Immediately after immersion, SBP, DBP, and MBP were significantly declined versus baseline. In contrast, the SCT was significantly increased after warm water immersion. However, all these parameters did not change significantly compared to the baseline within 30 min.
CONCLUSIONS: In the normal eye, parasympathetic nerve activity induced by warming stimuli increases choroidal morphology in response to a decrease in systemic circulatory activity, which normalizes within 30 min. The findings of this study may provide basic data for the prevention and treatment of various choroidal diseases in which sympathetic hyperactivity is involved in the pathogenesis.

BACKGROUND: Reduced vagally-mediated heart rate variability (HRV) has been associated with anxiety disorders (AD). The aim of this study was to use a wearable device and remote study design to re-evaluate the association of HRV with ADs, anxiety-related traits, and confounders.
METHODS: 240 individuals (AD = 120, healthy controls = 120) completed an at-home assessment of their short-term resting vagally-mediated HRV using a wristband, monitored over videoconference. Following quality control, analyses were performed investigating differences in HRV between individuals with AD (n = 119) and healthy controls (n = 116), associations of HRV with anxiety-related traits and confounders, and antidepressants effects on HRV in patients, including analyses stratified by ancestry (i.e., European, East Asian, African).
RESULTS: Among the confounders investigated, only age had a significant association with HRV. Patients with an AD had significantly lower vagally-mediated HRV than healthy controls in the European subsample, with a trend of significance in the whole sample. HRV was significantly associated with the Hamilton Anxiety Rating Scale (HAM-A) but not with antidepressant use in the European subsample.
CONCLUSIONS: The study measures occurred in a non-standardized at-home setting, and the three ancestry group sample sizes were unequal.
CONCLUSIONS: This study demonstrates reduced vagally-mediated HRV among patients with ADs compared to healthy controls. Results also point to low HRV being related to more physical anxiety symptoms (measured via HAM-A), suggesting a possible anxiety subtype. Overall, this study highlights the feasibility of using wearables for patients and encourages exploration of the biological and clinical utility of HRV as a risk factor for ADs.

We investigated the utility of heart rate (HR) and heart rate variability (HRV) for identifying individuals who may terminate work early due to excessive heat strain. Forty-eight men and women (median = 36 years; Q1 = 20 years; Q3 = 54 years) attempted 180 min of moderate-intensity work at a fixed metabolic rate (∼200 W/m2; ∼3.5 METs) in a hot environment (wet-bulb globe temperature: 32 °C). Receiver operating characteristics (ROC) curves were used to identify the ability of indices of HR (absolute HR, percentage of maximum HR, percentage of HR reserve) and HRV (root-mean-square of successive differences (RMSSD), high-frequency power, and detrended fluctuation analysis component alpha 1 (DFA α1)) to discriminate between participants who completed the 180 min work bout or terminated prematurely. Participants who terminated work prematurely (n = 26) exhibited higher HR and percentage of HR measures, as well as reduced RMSSD and DFA α1 after the first hour of work compared to participants who completed the bout. The discriminative utility of HR and HRV indices was strongest within the first hour of work, with percentage of HR reserve demonstrating excellent discriminative power (ROC area under curve (AUC) of 0.8). Stratifying participants by age and sex improved ROC AUC point estimates for most indices, particularly in female participants. The study provides preliminary evidence supporting the use of noninvasive cardiac monitoring for predicting work tolerance in healthy individuals exposed to occupational heat stress. HR and percentage of HR reserve were suggested to discriminate work termination most effectively. Further investigations are warranted to explore the influence of individual factors and refine the discriminative thresholds for early identification of excessive occupational heat strain.

Cardioneuroablation (CNA) is being increasingly used to treat patients with vasovagal syncope (VVS). Bradycardia, in the cardioinhibitory subtype of VVS, results from transient parasympathetic overactivity leading to sinus bradycardia and/or atrioventricular block. By mitigating parasympathetic overactivity, CNA has been shown to improve VVS symptoms in clinical studies with relatively small sample sizes and short follow-up periods (<5 years) at selected centers. However, CNA may potentially tip the autonomic balance to a state of sympathovagal imbalance with attenuation of cardiac parasympathetic activity. A higher heart rate is associated with adverse cardiovascular events and increased mortality in healthy populations without cardiovascular diseases. Chronic sympathovagal imbalance may also affect the pathophysiology of spectra of cardiovascular disorders including atrial and ventricular arrhythmias. This review addresses potential long-term pathophysiological consequences of CNA for VVS.

UNASSIGNED: Second-degree atrioventricular (AV) block at rest is very common in horses. The underlying molecular mechanisms are unexplored, but commonly attributed to high vagal tone.
UNASSIGNED: To assess whether AV block in horses is due to altered expression of the effectors of vagal signalling in the AV node, with specific emphasis on the muscarinic acetylcholine receptor (M2) and the G protein-gated inwardly rectifying K+ (GIRK4) channel that mediates the cardiac IK,ACh current.
UNASSIGNED: Eighteen horses with a low burden of second-degree AV block (median 8 block per 20 h, IQR: 32 per 20 h) were assigned to the control group, while 17 horses with a high burden of second-degree AV block (median: 408 block per 20 h, IQR: 1,436 per 20 h) were assigned to the AV block group. Radiotelemetry ECG recordings were performed to assess PR interval and incidence of second-degree AV block episodes at baseline and on pharmacological blockade of the autonomic nervous system (ANS). Wenckebach cycle length was measured by intracardiac pacing (n = 16). Furthermore, the expression levels of the M2 receptor and the GIRK4 subunit of the IKACh channel were quantified in biopsies from the right atrium, the AV node and right ventricle using immunohistochemistry and machine learning-based automated segmentation analysis (n = 9 + 9).
UNASSIGNED: The AV block group had a significantly longer PR interval (mean ± SD, 0.40 ± 0.05 s; p < 0.001) and a longer Wenckebach cycle length (mean ± SD, 995 ± 86 ms; p = 0.007) at baseline. After blocking the ANS, all second-degree AV block episodes were abolished, and the difference in PR interval disappered (p = 0.80). The AV block group had significantly higher expression of the M2 receptor (p = 0.02), but not the GIRK4 (p = 0.25) in the AV node compared to the control group. Both M2 and GIRK4 were highly expressed in the AV node and less expressed in the atria and the ventricles.
UNASSIGNED: Here, we demonstrate the involvement of the m2R-IK,ACh pathway in underlying second-degree AV block in horses. The high expression level of the M2 receptor may be responsible for the high burden of second-degree AV blocks seen in some horses.

BACKGROUND: This study aimed to examine the changes to choroidal blood flow velocity using laser speckle flowgraphy (LSFG) in healthy eyes after warm water immersion at 40°C.
METHODS: Data regarding the right eyes of 23 healthy volunteers were included. The mean blur rate (MBR) of the macula, which represents the choroidal blood flow velocity, was evaluated using LSFG. Intraocular pressure (IOP), systolic blood pressure (SBP), diastolic blood pressure (DBP), mean blood pressure (MBP), ocular perfusion pressure (OPP), and MBR were assessed at baseline, immediately after immersion (0 minutes), and 10, 20, and 30 minutes later.
RESULTS: At 0 minutes, SBP, DBP, MBP, and OPP values were lower than those at baseline. The MBR significantly declined immediately after immersion to -6.0 ± 5.2%. However, there were no changes in these parameters after 10, 20, or 30 minutes. A significant positive correlation was observed between the MBR, SBP, DBP, MBP, and OPP values. In healthy individuals, the dominant parasympathetic activity induced by warm stimulation reduced the choroidal hemodynamic rate in the macula and decreased systemic circulatory dynamics, which normalized after 10 minutes.
CONCLUSIONS: These findings suggest that the dominant parasympathetic activity induced by warm water immersion at 40°C may lead to a reduction in the systemic circulation rate and choroidal blood flow rate in the macula. These findings may help prevent and treat various retinal choroidal diseases, in which sympathetic hyperactivity is involved in the pathogenesis of the disease.

Most of the studies on the effect of trait positive affect (PA) and cardiovascular activity have focused on heart rate (HR) and blood pressure (BP) rather than heart rate variability (HRV). However, trait PA might sustain homeostasis for the autonomic system (ANS) by reducing activity in the sympathetic system (SNS) and increasing the activity in the parasympathetic system (PNS). A common index for the PNS is the vagal tone measured indirectly through HRV. The present study assessed whether trait PA influences cardiovascular response to various stress tasks by monitoring participants\' HRV measured by RMSSD (root mean square of successive differences) along with HR and interbeat interval (IBI). A total of 54 participants performed various cognitive tasks and Trier Social Stress Tasks while their vital signs were monitored, and trait PA was measured with PANAS. The cognitive tasks included both high- and low-stress tasks, including fatigue-inducing 20 min Stroop tasks. The results showed overall higher HRV as measured by RMSSD for participants who have higher levels of trait PA, indicating more PNS activity compared with low-trait-PA individuals, particularly at the end of the task performance during the fatigue induction. High-trait-PA individuals also had a lower HR during the fatigue-inducing task and a higher IBI. The results support previous work by further indicating a more adaptive response and consequently better emotional regulation for high-trait-PA individuals in a complex, prolonged task setting.