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Background: Several heart rate variability (HRV) parameters were reported to be associated with residual renal function (RRF) in patients undergoing continuous ambulatory peritoneal dialysis (CAPD). However, it is unclear whether using HRV or other autonomic nervous system (ANS) activity indexes can predict RRF decline in CAPD patients. Methods: Patients undergoing CAPD in 2022 from the First Affiliated Hospital of Nanjing Medical University were enrolled in this study. Their clinical characteristics, 5-min HRV parameters and average voltage of 5-min skin sympathetic nerve activity (aSKNA) were collected. According to the 12-month glomerular filtration rate (GFR) decline rate compared with the upper quartile, these patients were categorized into two groups: RRF decline (RRF-D) group and RRF stable (RRF-S) group. Clinical factors and ANS activity indexes for predicting 1-year RRF decline were analyzed using logistic regression, and a nomogram model was further established. The relationships between volume load related indexes and aSKNA were displayed by Spearman's correlation graphs. Results: Ninety-eight patients (53 women, average age of 46.7 ± 13.0 years old) with a median dialysis vintage of 24.5 months were enrolled in this study. Seventy-three patients were categorized into the RRF-S group and 25 patients into the RRF-D group. Compared with RRF-S group, patients in the RRF-D group had higher systolic blood pressure (BP; p = 0.019), higher GFR (p = 0.016), higher serum phosphorous level (p = 0.030), lower total Kt/V (p = 0.001), and lower levels of hemoglobin (p = 0.007) and albumin (p = 0.010). The RRF-D group generally exhibited lower HRV parameters and aSKNA compared with the RRF-S group. A nomogram model included clinical factors (sex, systolic BP, hemoglobin, GFR, and total Kt/V) and aSKNA showed the largest AUC of 0.940 (95% CI: 0.890–0.990) for predicting 1-year RRF decline. Conclusion: The nomogram model included clinical factors (sex, systolic BP, hemoglobin, GFR and total Kt/V) and ANS activity index (aSKNA) might be a promising tool for predicting 1-year RRF decline in CAPD patients. [ABSTRACT FROM AUTHOR]

Autonomic nerve activity is important in the mechanisms of paroxysmal atrial fibrillation (PAF). The purpose of this study was to test the hypothesis that a single burst of skin sympathetic nerve activity (SKNA) can toggle on and off PAF or premature atrial contraction (PAC) clusters. Simultaneous recording of SKNA and electrocardiogram (neuECG) recording was performed over 7 days in patients with PAF. In study 1, 8 patients (7 men and 1 woman; age 62 ± 8 years) had 124 episodes of PAF. An SKNA burst toggled both on and off PAF in 8 episodes (6.5%) (type 1), toggled on but not off in 12 episodes (9.7%) (type 2), and toggled on a PAC cluster followed by PAF in 4 episodes (3.2%) (type 3). The duration of these PAF episodes was <10 minutes. The remaining 100 episodes (80.6%) were associated with active SKNA bursts throughout PAF (type 4) and lasted longer than type 1 (P =.0185) and type 2 (P =.0027) PAF. There were 47 PAC clusters. Among them, 24 (51.1%) were toggled on and off, and 23 (48.9%) were toggled on but not off by an SKNA burst. In study 2, 17 patients (9 men and 8 women; age 58 ± 12 years) had <10 minutes of PAF (4, 8, 0, and 31 of types 1, 2, 3, and 4, respectively). There were significant circadian variations of all types of PAF. A single SKNA burst can toggle short-duration PAF and PAC cluster episodes on and off. The absence of continued SKNA after the onset might have affected the maintenance of these arrhythmias. [ABSTRACT FROM AUTHOR]

Abstract While autonomic dysregulation and repolarization abnormalities are observed in subarachnoid hemorrhage (SAH), their relationship remains unclear. We aimed to measure skin sympathetic nerve activity (SKNA), a novel method to estimate stellate ganglion nerve activity, and investigate its association with electrocardiogram (ECG) alterations after SAH. We recorded a total of 179 SKNA data from SAH patients at three distinct phases and compared them with 20 data from controls. Compared with control data, in the acute phase data (days 1–3 of SAH), T peak‐to‐end (Tp‐e) interval was significantly prolonged (81 [interquartile range {IQR}: 71–93] vs. 58 [IQR: 54–64] ms, p

Background: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) and dipeptidyl peptidase-4 inhibitors (DPP4i) are important second-line treatments for patients with type 2 diabetes mellitus (T2DM). Patients taking SGLT2i have favorable cardiovascular outcomes via various mechanisms, including autonomic nervous system (ANS) modulation. This study aimed to use neuroelectrocardiography (neuECG) to test the effects of SGLT2i or DPP4i on the ANS. Methods: Patients with T2DM, who did not reach target hemoglobin (Hb)A1C levels despite metformin treatment, were enrolled. SGLT2i or DPP4i were prescribed randomly unless a compelling indication was present. NeuECG and heart rate were recorded for 10 min before and after a 3-month treatment. The patients were treated according to standard practice and the obtained data for skin sympathetic nerve activity (SKNA) and ANS entropy were analyzed offline. Results: We enrolled 96 patients, of which 49 received SGLT2i and 47 received DPP4i. The baseline parameters were similar between the groups. No adverse event was seen during the study period. In the burst analysis of SKNA at baseline, all parameters were similar. After the 3-month treatment, the firing frequency was higher in SGLT2i group (0.104 ± 0.045 vs 0.083 ± 0.033 burst/min, p < 0.05), with increased long firing duration (7.34 ± 3.66 vs 5.906 ± 2.921, p < 0.05) in 3-s aSKNA scale; the other parameters did not show any significant change. By symbolic entropy, the most complex patterns (Rank 3) were found to be significantly higher in SGLT2i-treated patients than in DDP4i-treated group (0.084 ± 0.028 vs 0.07 ± 0.024, p = 0.01) and the direction of change in Rank 3, after SGLT2i treatment, was opposite to that observed in the DDP4i group (0.012 ± 0.036 vs. -0.005 ± 0.037, p = 0.024). Our findings demonstrated the favorable autonomic modulation by SGLTi and the detrimental effects of DPP4i on ANS. Conclusion: We demonstrated the autonomic modulation by SGLTi and DPP4i using SKNA in patients with DM, which might provide insights into the favorable outcomes of SGLT2i. Furthermore, we refined the analytical methods of neuECG, which uses SKNA to evaluate autonomic function. [ABSTRACT FROM AUTHOR]

Heart rate and vascular tension baroreflex exhibit resonance characteristics at approximately 0.1 and 0.03 Hz. In this study, we aimed to induce postural resonance (PR) through rhythmic postural adjustments. To assess the viability of this technique, we investigated the acute impacts of postural resonance on blood pressure, sympathetic nerve activity, and mood. Fifteen healthy study participants, consisting of 8 males and 7 females, were selected for this self-controlled study. Skin sympathetic nerve activity was continuously monitored during both the intervention and stress test on the experimental day. After PR intervention, the diastolic blood pressure and mean arterial pressure in the PR group exhibited significant reductions compared to the CON group (P = 0.032, CON = 71.67 ± 2.348, PR = 64.08 ± 2.35; P = 0.041, CON = 75.00 ± 2.17, PR = 81.67 ± 2.17). After PR intervention both left brachial ankle pulse wave velocity and right brachial ankle pulse wave velocity exhibited a significant reduction compared to pre-intervention levels (from 1115.86 ± 150.08 to 1048.43 ± 127.40 cm/s, p < 0.001; 1103.86 ± 144.35 to 1060.43 ± 121.35 cm/s, p = 0.018). PR intervention also led to a significant decrease in burst frequency and duration (P = 0.049; CON = 8.96 ± 1.17, PR = 5.51 ± 1.17) and a noteworthy decrease in burst amplitude and burst threshold during the cold-pressor test (P = 0.002; P = 0.002). Additionally, VAS scores exhibited a substantial increase following PR (P = 0.035, CON = 28.4 ± 4.49, PR = 42.17 ± 4.10). PR can induce resonance effects within the cardiovascular system, resulting in the effective reduction of blood pressure, skin sympathetic nerve activity and pulse wave velocity, and decreased burst amplitude and burst threshold of the sympathetic nerve during the cold-pressor test. [ABSTRACT FROM AUTHOR]

BackgroundSeveral heart rate variability (HRV) parameters were reported to be associated with residual renal function (RRF) in patients undergoing continuous ambulatory peritoneal dialysis (CAPD). However, it is unclear whether using HRV or other autonomic nervous system (ANS) activity indexes can predict RRF decline in CAPD patients.MethodsPatients undergoing CAPD in 2022 from the First Affiliated Hospital of Nanjing Medical University were enrolled in this study. Their clinical characteristics, 5-min HRV parameters and average voltage of 5-min skin sympathetic nerve activity (aSKNA) were collected. According to the 12-month glomerular filtration rate (GFR) decline rate compared with the upper quartile, these patients were categorized into two groups: RRF decline (RRF-D) group and RRF stable (RRF-S) group. Clinical factors and ANS activity indexes for predicting 1-year RRF decline were analyzed using logistic regression, and a nomogram model was further established. The relationships between volume load related indexes and aSKNA were displayed by Spearman's correlation graphs.ResultsNinety-eight patients (53 women, average age of 46.7 ± 13.0 years old) with a median dialysis vintage of 24.5 months were enrolled in this study. Seventy-three patients were categorized into the RRF-S group and 25 patients into the RRF-D group. Compared with RRF-S group, patients in the RRF-D group had higher systolic blood pressure (BP; p = 0.019), higher GFR (p = 0.016), higher serum phosphorous level (p = 0.030), lower total Kt/V (p = 0.001), and lower levels of hemoglobin (p = 0.007) and albumin (p = 0.010). The RRF-D group generally exhibited lower HRV parameters and aSKNA compared with the RRF-S group. A nomogram model included clinical factors (sex, systolic BP, hemoglobin, GFR, and total Kt/V) and aSKNA showed the largest AUC of 0.940 (95% CI: 0.890–0.990) for predicting 1-year RRF decline.ConclusionThe nomogram model included clinical factors (sex, systolic BP, hemoglobin, GFR and total Kt/V) and ANS activity index (aSKNA) might be a promising tool for predicting 1-year RRF decline in CAPD patients.

Abstract Cardioneuroablation (CNA) is currently considered as a promising treatment option for patients with symptomatic bradycardia caused by vagotonia. This study aims to further investigate its safety and efficacy in patients suffering from vagal bradycardia. A total of 60 patients with vagal bradycardia who underwent CNA in the First Affiliated Hospital of Xinjiang Medical University from November 2019 to June 2022. Preoperative atropine tests revealed abnormal vagal tone elevation in all patients. First, the electroanatomic structures of the left atrium was mapped out by using the Carto 3 system, according to the protocol of purely anatomy-guided and local fractionated intracardiac electrogram-guided CNA methods. The upper limit of ablation power of superior left ganglion (SLGP) and right anterior ganglion (RAGP) was not more than 45W with an ablation index of 450.Postoperative transesophageal cardiac electrophysiological examination was performed 1 to 3 months after surgery. The atropine test was conducted when appropriate. Twelve-lead electrocardiogram, Holter electrocardiogram, and skin sympathetic nerve activity were reviewed at 1, 3, 6 and 12 months after operation. Adverse events such as pacemaker implantation and other complications were also recorded to analyze the safety and efficacy of CNA in the treatment of vagus bradycardia. Sixty patients were enrolled in the study (38 males, mean age 36.67 ± 9.44, ranging from 18 to 50 years old). None of the patients had a vascular injury, thromboembolism, pericardial effusion, or other surgical complications. The mean heart rate, minimum heart rate, low frequency, low/high frequency, acceleration capacity of rate, and skin sympathetic nerve activity increased significantly after CNA. Conversely, SDNN, PNN50, rMSSD, high frequency, and deceleration capacity of rate values decreased after CNA (all P 0.05). The remaining 81.67% (49/60) of the patients had good clinical results, with no episodes of arrhythmia during follow-up. CNA may be a safe and effective treatment for vagal-induced bradycardia, subject to confirmation by larger multicenter trials.

Abstract Background Chemoradiotherapy (CRT), which might affect the autonomic system, is the mainstay therapy for advanced esophageal squamous cell carcinoma (ESCC). Autonomic dysfunction has been found to possibly lead to cancer mortality in those with elevated resting heart rates (RHR). Skin sympathetic nerve activity (SKNA) is a new method of stimulating electrical signals in skin to evaluate autonomic function from sympathetic tone. In this study, we investigated the association between changes in RHR and autonomic function and ESCC mortality. Methods Thirty-nine stage II-IV ESCC patients receiving CRT between March 2019 and November 2020 were prospectively enrolled and carefully selected, followed up and received the same meticulous supportive care. Serial RHR was recorded every two weeks from before CRT to eight weeks after CRT and average SKNA were recorded before and four weeks after CRT. All-cause mortality was defined as primary outcome. Results We found the RHR of ESCC patients to be significantly elevated and peaking at four weeks after CRT (p

Introduction: The function of the autonomic nervous system (ANS) is crucial in the development of intradialytic hypotension (IDH). This study introduced the entropy of heart rate variability (HRV) and skin sympathetic nerve activity (SKNA) to provide a complementary nonlinear and dynamic perspective for evaluating ANS function concerning IDH. Methods: 93 patients undergoing hemodialysis (HD) were enrolled, and the baseline data, electrocardiogram (ECG), and SKNA were collected. The patients were separated into the IDH and nonIDH groups based on the thresholds, which were characterized as reductions in systolic blood pressure (SBP) of at least 20 mm Hg or mean arterial pressure (MAP) of at least 10 mm Hg. We developed a logistic regression model for IDH after analyzing the changes in the time domain, frequency domain, the entropy of HRV, and SKNA indices during HD. Results: After 4-h HD, the detected results for heart rate, the ratio of low frequency and high frequency (LF/HF), and average SKNA (aSKNA) all increased in both groups. Nine out of the ten HRV indices and aSKNA in the nonIDH group were higher than those in the IDH group at most moments. aSKNA was positively correlated with heart rate (p = 0.0001) and LF/HF (p = 0.0005) in the nonIDH group, while the correlation disappeared in the IDH group, which indicated a worse ANS response in IDH patients. The logistic regression model exhibited the results of initial SBP [odds ratio (OR) 1.076; p = 0.001], and the difference between the last and first segments (DLF) of heart rate [OR 1.101; p =0.012] and LF/HF [OR 0.209; p =0.034], as well as the extreme value of the difference between other segments and the first segments (EOF) of aSKNA [OR 2.908; p =0.017], which were independent indicators for IDH. Discussion: The new nonlinear and dynamic assessment perspectives provided by the entropy of HRV and SKNA help to distinguish differences in ANS patterns between IDH patients and nonIDH patients and have the potential to be used in clinical monitoring for HD patients. [ABSTRACT FROM AUTHOR]

The neuromodulation effect after ventricular arrhythmia (VA) ablation is unclear. The study aimed to investigate skin sympathetic nerve activity (SKNA) changes in patients receiving catheter ablations for idiopathic VA. Of 43 patients with drug-refractory symptomatic VA receiving ablation, SKNA was continuously recorded for 10 min during resting from electrocardiogram lead I configuration and bipolar electrodes on the right arm 1 day before and 1 day after ablation. Twenty-two patients with acute procedure success and no recurrence during follow-ups were classified as sustained success group (group 1). Other 21 patients were classified as failed ablation group (group 2). Baseline SKNA showed no significant difference between the two groups. Post-ablation SKNA in group 2 was significantly higher than in group 1. In patients with ablation involved right ventricular outflow tract (RVOT), the post-ablation SKNA was also significantly higher in group 2. In contrast, there was no difference in post-ablation SKNA between groups in patients receiving non-RVOT ablation. The neuromodulation response after RVOT ablation may correspond to the sympathetic nerve distribution at RVOT. Augmentation of sympathetic activity after VA ablation indicates an unsuccessful VA suppression, especially in patients receiving ablation of RVOT VA. [Display omitted] • Neuromodulation can be observed after ablation of ventricular arrhythmia. • The change of sympathetic tone after ablation differs among patients. • Elevated post-ablation sympathetic tone indicates an unsuccessful right ventricular outflow tract ablation. [ABSTRACT FROM AUTHOR]

Background: Chemoradiotherapy (CRT), which might affect the autonomic system, is the mainstay therapy for advanced esophageal squamous cell carcinoma (ESCC). Autonomic dysfunction has been found to possibly lead to cancer mortality in those with elevated resting heart rates (RHR). Skin sympathetic nerve activity (SKNA) is a new method of stimulating electrical signals in skin to evaluate autonomic function from sympathetic tone. In this study, we investigated the association between changes in RHR and autonomic function and ESCC mortality.Methods: Thirty-nine stage II-IV ESCC patients receiving CRT between March 2019 and November 2020 were prospectively enrolled and carefully selected, followed up and received the same meticulous supportive care. Serial RHR was recorded every two weeks from before CRT to eight weeks after CRT and average SKNA were recorded before and four weeks after CRT. All-cause mortality was defined as primary outcome.Results: We found the RHR of ESCC patients to be significantly elevated and peaking at four weeks after CRT (p < 0.001) and then to gradually decrease. Those with an elevated RHR above the cutoff level (18 beat-per-minute) at eight weeks after CRT had worse overall survival. In addition, those with higher baseline sympathetic tone (average SKNA ≥ 0.86 μV) also had poor outcome.Conclusions: Increased pre-treatment sympathetic tone and elevated RHR after CRT are alarm signs of poor ESCC outcome. Further exploration of the mechanisms underlying these associations could potentially lead to intervention strategies for reducing mortality.Trial Registration: This study is registered with ClinicalTrials.gov, identifier: NCT03243448. [ABSTRACT FROM AUTHOR]

Background: Acute coronary syndrome (ACS) is major cause of ventricular arrhythmias (VAs) and sudden death. neuECG is a noninvasive method to simultaneously record skin sympathetic nerve activity (SKNA) and electrocardiogram.Objective: The purpose of this study was to test the hypotheses that (1) ACS increases average SKNA (aSKNA), (2) the magnitude of aSKNA elevation is associated with VAs during ACS, and (3) there is a gender difference in aSKNA between patients without and with ACS.Methods: We prospectively studied 128 ACS and 165 control participants. The neuECG was recorded with electrodes at Lead I configuration at baseline, during mental math stress, and during recovery (5 minutes for each phase). All recordings were done in the morning.Results: In the control group, women have higher aSKNA than do men at baseline (0.82 ± 0.25 μV vs 0.73 ± 0.20 μV; P = .009) but not during mental stress (1.21 ± 0.36 μV vs 1.16 ± 0.36 μV; P = .394), suggesting women had lower sympathetic reserve. In comparison, ACS is associated with equally elevated aSKNA in women vs men at baseline (1.14 ± 0.33 μV vs 1.04 ± 0.35 μV; P = .531), during mental stress (1.46 ± 0.32 μV vs 1.33 ± 0.37 μV; P = .113), and during recovery (1.30 ± 0.33 μV vs 1.11 ± 0.30 μV; P = .075). After adjusting for age and gender, the adjusted odds ratio for VAs including ventricular tachycardia and ventricular fibrillation is 1.23 (95% confidence interval 1.05-1.44) for each 0.1 μV aSKNA elevation. aSKNA is positively correlated with plasma norepinephrine level.Conclusion: ACS is associated with elevated aSKNA, and the magnitude of aSKNA elevation is associated with the occurrence of VAs. Women have higher aSKNA and lower SKNA reserve than do men among controls but not among patients with ACS. [ABSTRACT FROM AUTHOR]

Background: Autonomic nerve system (ANS) plays an important role in regulating cardiovascular function and cerebrovascular function. Traditional heart rate variation (HRV) and emerging skin sympathetic nerve activity (SKNA) analyses from ultra-short-time (UST) data cannot fully reveal neural activity, thereby quantitatively reflect ANS intensity. Methods: Electrocardiogram and SKNA from sixteen patients (seven cerebral hemorrhage (CH) patients and nine control group (CO) patients) were recorded using a portable device. Ten derived HRV (mean, standard deviation and root mean square difference of sinus RR intervals (NNmean, SDNN and RMSSD), ultra-low frequency (<0.003 Hz, uLF), very low frequency ([0.003 Hz, 0.04 Hz), vLF), low frequency ([0.04 Hz, 0.15 Hz), LF) and high frequency power ([0.15 Hz, 0.4 Hz), HF), ratio of LF to HF (LF/HF), the standard deviation of instantaneous beat-to-beat R-R interval variability (SD1), and approximate entropy (ApEn)) and ten visibility graph (VG) features (diameter (Dia), average node degree (aND), average shortest-path length (aSPL), clustering coefficient (CC), average closeness centrality (aCC), transitivity (Trans), average degree centrality (aDC), link density (LD), sMetric (sM) and graph energy (GE) of the constructed complex network) were compared on 5-min and UST segments to verify their validity and robustness in discriminating CH and CO under different data lengths. Besides, their potential for quantifying ANS-Load were also investigated. Results: The validation results of HRV and VG features in discriminating CH from CO showed that VG features were more clearly distinguishable between the two groups than HRV features. For effectiveness evaluation of analyzing ANS on UST segment, the NNmean, SDNN, RMSSD, LF, HF and LF/HF in HRV features and the CC, Trans, Dia and GE of VG features remained stable in both activated and inactivated segments across all data lengths. The capability of HRV and VG features in quantifying ANS-Load were evaluated and compared under different ANS-Load, the results showed that most HRV features (SDNN, LFHF, RMSSD, vLF, LF and HF) and almost all VG features were correlated to sympathetic nerve activity intensity. Conclusions: The proposed autonomic nervous activity analysis method based on VG and SKNA offers a new insight into ANS assessment in UST segments and ANS-Load quantification. [ABSTRACT FROM AUTHOR]

BackgroundPulmonary vein isolation (PVI) is the cornerstone of atrial fibrillation (AF) ablation. Success is associated with autonomic function modulation; however, the relationship between the changes after ablation is not fully understood. We aimed to investigate the effect of ablation on autonomic modulation by skin sympathetic nerve activity (SKNA) using conventional electrocardiogram (ECG) electrodes and to predict the treatment success.MethodsWe enrolled 79 patients. We recorded neuECG for 10 min at 10 kHz before and after ablation. The NeuECG was bandpass-filtered (500–1,000 Hz) and integrated at intervals of 100 ms (iSKNA). iSKNA was averaged over different time windows (1-, 5-,10-s; aSKNAs), and burst analyses were derived from aSKNAs to quantify the dynamics of sympathetic activities. AF recurrence after 3 months was defined as the study endpoint.ResultsSixteen patients experienced AF recurrence after the ablation. For burst analysis of 1-s aSKNA, the recurrence group had a higher bursting frequency than the non-recurrence group (0.074 ± 0.055 vs. 0.109 ± 0.067; p < 0.05) before ablation. The differences between pre- and post-ablation of firing duration longer than 2 s were more in the non-recurrence group (2.75 ± 6.41 vs. −1.41 ± 5.14; p < 0.05), while no significant changes were observed in the percentage of duration longer than 10 s using 5-s aSKNA. In addition, decreases in differences in firing frequency and percentage of both overall firing duration and longer firing duration (> 2 s) between pre- and post-ablation were independently associated with AF recurrence and more area under receiver operating characteristics (ROC) curve in combination with CHADS2 score (0.833).ConclusionWe demonstrated the applicability of neuECG for determining sympathetic modulation during AF ablation. Decreasing sympathetic activity is the key to successful ablation.

Autonomic system plays a pivotal role in the pathogenesis of paroxysmal atrial fibrillation (AF). Skin sympathetic nerve activity (SKNA) is a noninvasive tool for assessing sympathetic tone. However, data on changes in SKNA after ablation are limited. Here, we retrospectively enrolled 37 patients with symptomatic drug-refractory paroxysmal AF who underwent pulmonary vein isolation (PVI) with radiofrequency ablation (RFA) or cryoablation (CBA). SKNA was measured from the chest and right arm 1 day prior to ablation, as well as 1 day and 3 months after ablation. One day after ablation, the SKNA-Arm increased from 517.1 µV (first and third quartiles, 396.0 and 728.0, respectively) to 1226.2 µV (first and third quartiles, 555.2 and 2281.0), with an increase of 179.8% (125% and 376.0%) (p < 0.001); the SKNA-Chest increased from 538.2 µV (first and third quartiles, 432.9 and 663.9) to 640.0 µV (first and third quartiles, 474.2 and 925.6), with an increase of 108.3% (95.6% and 167.9%) (p = 0.004), respectively. In those without recurrence, there was a significant increase in SKNA 1 day after ablation as compared with those before ablation. Twelve patients received SKNA measurement 3 months after ablation; both SKNA-Arm (p = 0.31) and SKNA-Chest (p = 0.27) were similar to those before ablation, respectively. Among patients with symptomatic drug-refractory paroxysmal AF receiving PVI, increased SKNA was observed 1 day after ablation and returned to the baseline 3 months after ablation. Elevation of SKNA was associated with lower early and late recurrences following ablation. [ABSTRACT FROM AUTHOR]

Background: The skin sympathetic nerve activity (SKNA) is a new method to measure sympathetic nerve activity by using conventional ECG electrodes. We developed a novel approach to analyze the complexity of SKNA time series under different time scales and showed its prognostic significance in patients receiving critical care. Methods: This study measured SKNA in patients admitted to an intensive care unit (ICU). Each recording is 10-minute long with 10000Hz sampling rate. Multi-scale fluctuation analysis (MSFA) was developed to quantify the variation within each time scale after removing the linear trend. The prognostic value of SKNA was combined with traditional prognostics scoring system to improve the predictive values. Results: 155 patients were recruited. After 30 and 90 days, 30 and 48 patients expired. MSFA was significantly higher in survival group than mortality group for 30-day (0.487 ± 0.185 vs 0.401 ± 0.045, p = 0.018) and 90-day (0.499 ± 0.196 vs 0.414 ± 0.061, p = 0.001) follow-up. Sequential Organ Failure Assessment (SOFA) score was significantly lower in the survival group compared to the expired group for 30-day and 90-day (4.1 ± 2.9 vs. 5.5 ± 4.1, p = 0.032 and 3.9 ± 3.0 vs. 5.4 ± 3.5, p = 0.012). The Kaplan–Meier survival analysis showed MSFA lower than 0.401 (log-rank test:4.96, p = 0.03) or with SOFA score lower than 5 (log-rank test:5.49, p = 0.019) have a significantly higher mortality rate. A multivariate Cox regression model showed that the MSFA is an independent predictor for 30-day mortality (HR = 2.35, 1.08–5.09, p = 0.031) and 90-day mortality (HR = 1.96, 1.08–3.58, p = 0.027). Conclusion: MSFA was a significant prognostic predictor for critically ill patients. MSFA adding to SOFA score could help improve risk prediction.

Background: Autonomic nervous regulation plays a critical role in end-stage kidney disease (ESKD) patients with cardiovascular complications. However, studies on autonomic regulation in ESKD patients are limited to heart rate variability (HRV) analysis. Skin sympathetic nerve activity (SKNA), which noninvasively reflects the sympathetic nerve activity, has not been used in ESKD patients. Methods: Seventy-six patients on maintenance hemodialysis (MHD) treatment (a 4-h HD session, three times a week) were enrolled. Utilizing a noninvasive, single-lead, high-frequency recording system, we analyzed the dynamic change in HRV parameters and SKNA during HD. The different characteristics between the subgroups divided based on interdialytic weight gain (IDWG, <3 kg or ≥3 kg) were also demonstrated. Results: After the HD, values for heart rate (75.1 ± 11.3 to 80.3 ± 12.3 bpm, p < 0.001) and LF/HF (1.92 ± 1.67 to 2.18 ± 2.17, p = 0.013) were significantly higher than baseline. In subgroup analysis, average voltage of skin sympathetic nerve activity (aSKNA) in IDWG ≥3 kg group was lower than the IDWG <3 kg group at the end of MHD (1.06 ± 0.30 vs 1.32 ± 0.61 μV, p = 0.046). Moreover, there was a linear correlation between mean heart rate (HR) and aSKNA in low IDWG patients (p < 0.001), which was not found in high IDWG patients. At the 1-year follow-up, high IDWG patients had a higher incidence of cardiovascular hospitalization (p = 0.046). Conclusions: In MHD patients, a gradual activation of sympathetic nerve activity could be measured by HRV and aSKNA. A lower aSKNA at the end of HD and a loss of HR-aSKNA correlation in overhydrated patients were observed. Extensive volume control is promising to improve the autonomic nervous function and clinical outcomes in this population. [ABSTRACT FROM AUTHOR]

Background: Autonomic nervous regulation plays a critical role in end-stage kidney disease (ESKD) patients with cardiovascular complications. However, studies on autonomic regulation in ESKD patients are limited to heart rate variability (HRV) analysis. Skin sympathetic nerve activity (SKNA), which noninvasively reflects the sympathetic nerve activity, has not been used in ESKD patients.Methods: Seventy-six patients on maintenance hemodialysis (MHD) treatment (a 4-h HD session, three times a week) were enrolled. Utilizing a noninvasive, single-lead, high-frequency recording system, we analyzed the dynamic change in HRV parameters and SKNA during HD. The different characteristics between the subgroups divided based on interdialytic weight gain (IDWG,

Background: Obstructive sleep apnea (OSA) is associated with cardiovascular diseases and increased sympathetic tone. We previously demonstrated that patients with OSA have increased skin sympathetic nerve activity (SKNA).Objective: The purpose of this study was to test the hypothesis that continuous positive airway pressure (CPAP) treatment reduces SKNA.Methods: The electrocardiogram, SKNA, and polysomnographic recording were recorded simultaneously in 9 patients with OSA. After baseline recording, CPAP titration was performed and the pressure was adjusted gradually for the optimal treatment, defined by reducing the apnea-hypopnea index (AHI) to ≤5/h. Otherwise the treatment was considered suboptimal (AHI > 5/h). Fast Fourier transform analyses were performed to investigate the frequency spectrum of SKNA.Results: There were very low frequency (VLF), low frequency (LF), and high frequency (HF) oscillations in SKNA. The HF oscillation matched the frequency of respiration. OSA episodes were more frequently associated with the VLF and LF than with the HF oscillations of SKNA. Compared with baseline, CPAP significantly decreased the arousal index and AHI and increased the minimal and mean oxyhemoglobin levels. Optimal treatment significantly increased the dominant frequency and reduced the heart rate, average SKNA (aSKNA), SKNA burst duration, and total burst area. The dominant frequency negatively correlated with aSKNA.Conclusion: VLF, LF, and HF oscillations are observed in human SKNA recordings. Among them, VLF and LF oscillations are associated with OSA while HF oscillations are associated with normal breathing. CPAP therapy reduces aSKNA and shifts the frequency of SKNA oscillation from VLF or LF to HF. [ABSTRACT FROM AUTHOR]

• Various types of cerebellar degeneration syndrome are often complicated with autonomic symptoms or dysfunction. • Skin vasomotor function including sympathetic nerve activity (SSNA) was not evaluated in DRPLA. • The resting SSNA was lower and the latency of SSNA reflex bursts prolonged in a patient with DRPLA. • This is the first report to record SSNA and confirm subclinical autonomic dysfunction in a case with DRPLA. Dentatorubral-pallidoluysian atrophy (DRPLA) is an autosomal dominant neurodegenerative disorder characterized by slowly progressive cerebellar ataxia. Previously, autonomic symptoms or dysfunction have not been reported. To evaluate subclinical autonomic dysfunction regarding thermoregulatory function in SCA, we recorded sympathetic outflow to skin in a DRPLA patient confirmed by genetic analysis. We recorded skin sympathetic nerve activity (SSNA), which was elicited and recorded by using the microneurographical technique. In results, the resting frequency of SSNA bursts was very low (8.2 ± 0.4 bursts/min [institutional normal range: 20.8 ± 2.4 bursts/min]). However, acceleration of SSNA bursts induced by mental arithmetic stress was confirmed. The amplitude of reflex bursts induced by electrical stimuli was slightly low (9.6 ± 1.6 μV [institutional normal range: 10.9 ± 2.2 μV]), and the reflex latency was mildly prolonged (872 ± 23.7 msec [institutional normal range: 761.9 ± 51.7 msec]). These results suggest potentially central autonomic dysfunction in this patient with DRPLA. To our knowledge, this is the first report to record SSNA and confirm subclinical autonomic dysfunction in a case with DRPLA. [ABSTRACT FROM AUTHOR]

Background: Sympathetic nerve activity, heart rate (HR), and blood pressure (BP) all have very low frequency (VLF), low frequency (LF), and high frequency (HF) oscillations.Objective: The purpose of this study was to test the hypothesis that the frequency spectra of subcutaneous nerve activity (ScNA), stellate ganglion nerve activity (SGNA), HR, and BP are important to cardiac arrhythmogenesis.Methods: We used radiotransmitters to record SGNA, ScNA, HR, and BP in 6 ambulatory dogs and determined the dominant frequency and paroxysmal atrial tachyarrhythmias (PATs) episodes in 3-minute windows over a 24-hour period.Results: The frequency spectra determined in ScNA reflected that in SGNA. HF oscillations were present in both ScNA and SGNA at all time but could be overshadowed by the much larger LF and VLF burst activities. The dominant frequency could occur in any of the 3 frequency bands. There were circadian variations with more frequent occurrences of HF oscillations at night. HF oscillations in HR and BP matched HF oscillations in SGNA and ScNA. PATs occurred only when dominant frequencies of SGNA and ScNA were in the LF and VLF bands.Conclusion: HF oscillations in BP and HR correlate with HF oscillations in sympathetic nerve activity and are present at all time. HF oscillations can be overshadowed by the much larger LF and VLF burst activities. PATs occur only when LF or VLF, but not when HF, is the dominant frequency. The frequency spectra determined in ScNA reflect that in SGNA. [ABSTRACT FROM AUTHOR]

The development of microneurography, in which the electrical activity of axons can be recorded via an intrafascicular microelectrode inserted through the skin into a peripheral nerve in awake human participants, has contributed a great deal to our understanding of sensorimotor control and the control of sympathetic outflow to muscle and skin. This review summarises the different approaches to recording muscle sympathetic nerve activity (MSNA) and skin sympathetic nerve activity (SSNA), together with discussion on the issues that determine the quality of a recording. Various analytical approaches are also described, with a primary emphasis on those developed by the author, aimed at maximizing the information content from recordings of postganglionic sympathetic nerve activity in awake humans. [ABSTRACT FROM AUTHOR]

Background: The skin sympathetic nerve activity (SKNA) is a new method to measure sympathetic nerve activity by using conventional ECG electrodes. We developed a novel approach to analyze the complexity of SKNA time series under different time scales and showed its prognostic significance in patients receiving critical care.Methods: This study measured SKNA in patients admitted to an intensive care unit (ICU). Each recording is 10-minute long with 10000Hz sampling rate. Multi-scale fluctuation analysis (MSFA) was developed to quantify the variation within each time scale after removing the linear trend. The prognostic value of SKNA was combined with traditional prognostics scoring system to improve the predictive values.Results: 155 patients were recruited. After 30 and 90 days, 30 and 48 patients expired. MSFA was significantly higher in survival group than mortality group for 30-day (0.487 ± 0.185 vs 0.401 ± 0.045, p = 0.018) and 90-day (0.499 ± 0.196 vs 0.414 ± 0.061, p = 0.001) follow-up. Sequential Organ Failure Assessment (SOFA) score was significantly lower in the survival group compared to the expired group for 30-day and 90-day (4.1 ± 2.9 vs. 5.5 ± 4.1, p = 0.032 and 3.9 ± 3.0 vs. 5.4 ± 3.5, p = 0.012). The Kaplan-Meier survival analysis showed MSFA lower than 0.401 (log-rank test:4.96, p = 0.03) or with SOFA score lower than 5 (log-rank test:5.49, p = 0.019) have a significantly higher mortality rate. A multivariate Cox regression model showed that the MSFA is an independent predictor for 30-day mortality (HR = 2.35, 1.08-5.09, p = 0.031) and 90-day mortality (HR = 1.96, 1.08-3.58, p = 0.027).Conclusion: MSFA was a significant prognostic predictor for critically ill patients. MSFA adding to SOFA score could help improve risk prediction. [ABSTRACT FROM AUTHOR]

Atrial fibrillation (AF) is the most common cardiac arrhythmia and is associated with an increased risk of all-cause mortality and complications. The autonomic nervous system (ANS) plays a central role in AF, with the heart regulated by both extrinsic and intrinsic properties. In the extrinsic ANS, the sympathetic fibers are derived from the major paravertebral ganglia, especially the stellate ganglion (SG), which is a source of cardiac sympathetic innervation since it connects with multiple intrathoracic nerves and structures. The major intrinsic ANS is a network of axons and ganglionated plexi that contains a variety of sympathetic and parasympathetic neurons, which communicate with the extrinsic ANS. Simultaneous sympathovagal activation contributes to the development of AF because it increases calcium entry and shortens the atrial action potential duration. In animal and human studies, neuromodulation methods such as electrical stimulation and renal denervation have indicated potential benefits in controlling AF in patients as they cause SG remodeling and reduce sympathetic outflow. This review focuses on the neural mechanisms relevant to AF and the recent developments of neuromodulation methods for AF control. [ABSTRACT FROM AUTHOR]

Sopite syndrome, centered around the drowsiness, lethargy, and irritability associated with motion sickness, can be induced by exposure to low-frequency motion. It is known that the vestibular apparatus plays an important role in the pathogenesis of motion sickness, which features several autonomic responses, and we have previously documented increased vestibular modulation of skin sympathetic nerve activity (SSNA) and an increase in skin blood flow associated with nausea. Here, we assessed whether imperceptibly slow sinusoidal motion, sufficient to induce sopite syndrome but not nausea, also modulates SSNA and skin blood flow. Participants were seated upright and exposed to a randomized set of sinusoidal linear accelerations, ranging from 0.03 Hz at 0.5 mG to 0.2 Hz at 5 mG, via a motorized platform. At all frequencies vestibular modulation was greater than the cardiac modulation of SSNA, but cardiac modulation and skin blood flow were both significantly lower during the motion than at baseline. We conclude that sopite syndrome is associated with a marked modulation of sympathetic outflow to the skin and cutaneous vasoconstriction. [ABSTRACT FROM AUTHOR]

Background: Obstructive sleep apnea (OSA) is associated with increased cardiac arrhythmia and sudden cardiac death. We recently developed a new method (neuECG) to noninvasively measure electrocardiogram and skin sympathetic nerve activity (SKNA).Objective: The purpose of this study was to test the hypothesis that SKNA measured during sleep study is higher in patients with OSA than in those without OSA.Methods: We prospectively recorded neuECG and polysomnography in 26 patients undergoing a sleep study. Sleep stages were scored into rapid eye movement (REM), and non-REM sleep stages 1 (N1), 2 (N2), and 3 (N3). Average voltage of skin sympathetic nerve activity (aSKNA) and SKNA burst area were calculated for quantification. Apnea/hypopnea index (AHI) >5 per hour was used to diagnose OSA.Results: There was a positive correlation (r = 0.549; P = .018) between SKNA burst area and the arousal index in OSA but not in the control group. aSKNA during sleep was 0.61 ± 0.09 μV in OSA patients (n = 18) and 0.53 ± 0.04 μV in control patients (n = 8; P = .025). Burst area was 3.26 (1.90-4.47) μV·s/min in OSA patients and 1.31 (0.67-1.94) μV·s/min in control (P = .047). More apparent differences were found during N2, when the burst area in OSA (3.06 [1.46-5.52] μV·s/min) was much higher than that of the control (0.89 [0.79-1.65] μV·s/min; P = .03).Conclusion: OSA patients have higher SKNA activity than control patients, with the most pronounced differences observed during N2. Arousal at the end of apnea episodes is associated with large SKNA bursts. Overlaps of aSKNA and SKNA burst area between groups suggest that not all OSA patients have increased sympathetic tone. [ABSTRACT FROM AUTHOR]

Background: Although left cardiac sympathetic denervation (LCSD) is an effective antiarrhythmic therapy for patients with long QT syndrome (LQTS), direct evidence of reduced sympathetic activity after LCSD in humans is limited.Objective: The purpose of this study was to assess skin sympathetic nerve activity (SKNA) in patients with LQTS undergoing LCSD.Methods: We prospectively enrolled 17 patients with LQTS who underwent LCSD between 2017 and 2019. SKNA recordings from the left arm (L-SKNA) and chest (C-SKNA) leads were performed before and after LCSD. Mean SKNA, burst activity, and nonburst activity of L-SKNA and C-SKNA were analyzed.Results: The mean patient age was 21 ± 9 years (8 men 47%). The longest baseline corrected QT value was 497 ± 55 ms at rest and 531 ± 38 ms on exercise stress testing. Five patients (29.4%) had previous LQTS-triggered cardiac events including syncope, documented torsades de pointes, and ventricular fibrillation. In the 24 hours after LCSD, mean L-SKNA decreased from 1.25 ± 0.64 to 0.85 ± 0.33 μV (P = .005) and mean C-SKNA from 1.36 ± 0.67 to 1.05 ± 0.49 μV (P = .11). The frequency of episodes of SKNA bursts recorded from the left-arm lead (2.87 ± 1.61 bursts per minute vs 1.13 ± 0.99 bursts per minute; P < .001) and mean L-SKNA during burst (1.82 ± 0.79 μV vs 1.15 ± 0.44 μV; P < .001) and nonburst (1.09 ± 0.60 μV vs 0.75 ± 0.32 μV; P = .03) periods significantly decreased after LCSD, while the frequency of episodes of SKNA bursts recorded from the chest lead (P = .57) and mean C-SKNA during burst (P = .44) and nonburst (P = .10) periods did not change significantly. No arrhythmic events were documented after 11.9 months (range 3.0-22.2 months) of follow-up.Conclusion: LCSD provides an inhibitory effect on cardiac sympathetic activity by suppressing burst discharge as measured by SKNA. [ABSTRACT FROM AUTHOR]

Background: To find out the physiological method for evaluating the severity of central autonomic dysfunction, we performed detailed evaluation of cutaneous vasomotor neural function in a comparatively large sample of multiple system atrophy (MSA). Methods: We evaluated cutaneous vasomotor neural function in 24 MSA patients. Skin sympathetic nerve activity (SSNA) and sympathetic skin response (SSR) and skin blood flow (skin vasomotor reflex [SVR]) were recorded at rest, as well as reflex changes after electrical stimulation. The parameters investigated were SSNA frequency at rest, reflex latency and amplitude of SSNA reflex bursts, absolute decrease and percent reduction of SVR, recovery time, and spontaneous SVR and SSR frequency. Results: There were negative correlations between resting SSNA and disease duration or the SCOPA-AUT score, but these were not significant. SSNA reflex latency displayed significant positive correlations with disease duration and SCOPA-AUT score (p < 0.001 and p < 0.01, respectively). In all five patients who underwent the same examination twice, SSNA reflex latency was significantly longer at the second examination than at the first examination (p < 0.005). A significant positive correlation was identified between recovery time of skin blood flow and SCOPA-AUT score or reflex latency (p < 0.05). Significant correlations were not observed between SCOPA-AUT score or disease duration and other parameters. Conclusions: These results suggest that some MSA patients with a comparatively short duration of disease potentially have impaired thermoregulatory function. Measurement of sympathetic outflow to the skin is potentially a useful tool for predicting the severity of central autonomic dysfunction in MSA. [ABSTRACT FROM AUTHOR]

Background: Heightened sympathetic nerve activity has been associated with poorer prognosis in patients with reduced left ventricular systolic function (ie, heart failure with reduced ejection fraction [HFrEF]).Objective: The purpose of this study was to investigate the effects of cardiac resynchronization therapy (CRT) on sympathetic nerve activity, measured by average skin sympathetic nerve activity (aSKNA).Methods: This prospective study enrolled 36 patients with HFrEF who received CRT. Ten patients who received an implantable cardioverter-defibrillator for primary prevention served as controls. Patient clinical data, echocardiographic variables, and aSKNA at baseline and 3-month follow-up were collected.Results: CRT patients who exhibited wider QRS duration had higher aSKNA (1.52 ± 0.65 μV vs 0.97 ± 0.49 μV; P = .027) compared to the control group at baseline. In the CRT group, patients with QRS duration ≥150 ms had higher aSKNA than those with QRS duration <150 ms (1.67 ± 0.63 μV vs 1.19 ± 0.51 μV; P =.039). After CRT, left ventricular ejection fraction (LVEF) improved from 29.6% to 35.4% (P = .001). aSKNA decreased significantly (1.52 ± 0.65 μV vs 1.31 ± 0.63 μV; P = .018). Seventeen of the 36 CRT patients were CRT responders, with LVEF improvement ≥5% at 3-month follow-up. aSKNA significantly decreased from 1.47 to 1.15 μV (P = .003) in CRT responders but was unchanged in nonresponders (1.44 ± 0.69 to 1.37 ± 0.70; P = .61). After CRT, a significant reduction in aSKNA was associated with improvement in LVEF (r = 0.638; P = .001).Conclusion: CRT reduces elevated sympathetic activity in HFrEF patients, accompanied by improvement in systolic function at short-term follow-up. The reduction of sympathetic activity is mainly seen in CRT responders. [ABSTRACT FROM AUTHOR]

Background: Autonomic imbalance is the proposed mechanism of syncope during a tilt table test (TTT). We have recently demonstrated that skin sympathetic nerve activity (SKNA) can be noninvasively recorded using electrocardiographic electrodes.Objective: The purpose of this study was to test the hypothesis that increased SKNA activation precedes tilt-induced syncope.Methods: We studied 50 patients with a history of neurocardiogenic syncope undergoing a TTT. The recorded signals were band-pass filtered at 500-1000 Hz to analyze nerve activity.Results: The average SKNA (aSKNA) value at baseline was 1.38 ± 0.38 μV in patients without syncope and 1.42 ± 0.52 μV in patients with syncope (P = .77). On upright tilt, aSKNA was 1.34 ± 0.40 μV in patients who did not have syncope and 1.39 ± 0.43 μV in patients who had syncope (P = .65). In all 14 patients with syncope, there was a surge of SKNA before an initial increase in heart rate followed by bradycardia, hypotension, and syncope. The peak aSKNA immediately (<1 minute) before syncope was significantly higher than baseline aSKNA (2.63 ± 1.22 vs 1.39 ± 0.43 μV; P = .0005). After syncope, patients were immediately placed in the supine position and aSKNA dropped significantly to 1.26 ± 0.43 μV; (P = .0004). The heart rate variability during the TTT shows a significant increase in parasympathetic tone during syncope (low-frequency/high-frequency ratio: 7.15 vs 2.21; P = .04).Conclusion: Patients with syncope do not have elevated sympathetic tone at baseline or during the TTT except immediately before syncope when there is a transient surge of SKNA followed by sympathetic withdrawal along with parasympathetic surge. [ABSTRACT FROM AUTHOR]

Background: The relationship between the ventricular rate (VR) during atrial fibrillation (AF) and skin sympathetic nerve activity (SKNA) remains unclear.Objective: The purpose of this study was to test the hypothesis that SKNA bursts accelerate VR during AF.Methods: We simultaneously recorded electrocardiogram and SKNA in 8 patients (median age 66.0 years [interquartile range {IQR} 59.0-77.0 years]; 4 men [50%]) with 30 paroxysmal AF episodes (all >10-minute long) and 12 patients (73.0 years [IQR 60.5-80.0 years]; 6 men [50%]) with persistent AF. The average amplitude of SKNA (aSKNA [μV]) during AF was analyzed in 1-minute windows and binned, showing 2 Gaussian distributions. We used the mean + 3SD of the first Gaussian distribution as the threshold that separates burst from baseline (nonburst) SKNA. All 1-minute aSKNA values above the threshold were detected, and the area between aSKNA and baseline of every 1 minute was calculated and added as burst area.Results: VR was higher during SKNA bursts than during the nonburst period (103 beats/min [IQR 83-113 beats/min] vs 88 beats/min [IQR 76-101 beats/min], respectively; P = .003). In the highest quartile of the burst area during persistent AF, the scatterplot of maximal aSKNA and VR during each SKNA burst shows higher aSKNA and VR. The overall estimate of the correlation between maximal VR and aSKNA during bursts show a positive correlation in the highest quartile of the burst area (0.64; 95% confidence interval 0.54-0.74; P < .0001).Conclusion: SKNA bursts are associated with VR acceleration. These SKNA bursts may be new therapeutic targets for rate control during AF. [ABSTRACT FROM AUTHOR]

Key points: With the advent of more frequent extreme heat events, adaptability to hot environments will be crucial for the survival of many species, including humans. However, the mechanisms that mediate human heat adaptation have remained elusive.We tested the hypothesis that heat acclimation improves the neural control of body temperature. Skin sympathetic nerve activity, comprising the efferent neural signal that activates heat loss thermoeffectors, was measured in healthy adults exposed to passive heat stress before and after a 7 day heat acclimation protocol.Heat acclimation reduced the activation threshold for skin sympathetic nerve activity, leading to an earlier activation of cutaneous vasodilatation and sweat production. These findings demonstrate that heat acclimation improves the neural control of body temperature in humans. Heat acclimation improves autonomic temperature regulation in humans. However, the mechanisms that mediate human heat adaptation remain poorly understood. The present study tested the hypothesis that heat acclimation improves the neural control of body temperature. Body temperatures, skin sympathetic nerve activity, cutaneous vasodilatation, and sweat production were measured in 14 healthy adults (nine men and five women, aged 27 ± 5 years) during passive heat stress performed before and after a 7 day heat acclimation protocol. Heat acclimation increased whole‐body sweat rate [+0.54 L h–1 (0.32, 0.75), P < 0.01] and reduced resting core temperature [–0.29°C (–0.40, –0.18), P < 0.01]. During passive heat stress, the change in mean body temperature required to activate skin sympathetic nerve activity was reduced [–0.21°C (–0.34, –0.08), P < 0.01] following heat acclimation. The earlier activation of skin sympathetic nerve activity resulted in lower activation thresholds for cutaneous vasodilatation [–0.18°C (–0.35, –0.01), P = 0.04] and local sweat rate [–0.13°C (–0.24, –0.01), P = 0.03]. These results demonstrate that heat acclimation leads to an earlier activation of the neural efferent outflow that activates the heat loss thermoeffectors of cutaneous vasodilatation and sweating. Key points: With the advent of more frequent extreme heat events, adaptability to hot environments will be crucial for the survival of many species, including humans. However, the mechanisms that mediate human heat adaptation have remained elusive.We tested the hypothesis that heat acclimation improves the neural control of body temperature. Skin sympathetic nerve activity, comprising the efferent neural signal that activates heat loss thermoeffectors, was measured in healthy adults exposed to passive heat stress before and after a 7 day heat acclimation protocol.Heat acclimation reduced the activation threshold for skin sympathetic nerve activity, leading to an earlier activation of cutaneous vasodilatation and sweat production. These findings demonstrate that heat acclimation improves the neural control of body temperature in humans. [ABSTRACT FROM AUTHOR]

Background: Modifying the autonomic system after catheter ablation may prevent the recurrence of atrial fibrillation (AF). Evaluation of skin sympathetic nerve activity (SKNA) is a noninvasive method for the assessment of sympathetic activity. However, there are few studies on the effects of different energy settings on SKNA., Objective: To investigate the changes in SKNA in different energy settings and their relationship to AF ablation outcomes., Methods: Seventy-two patients with paroxysmal and persistent AF were enrolled. Forty-three patients received AF ablation with the conventional (ConV) energy setting (low power for long duration), and 29 patients using a high-power, short-duration (HPSD) strategy. The SKNA was acquired from the right arm 1 day before and after the radiofrequency ablation. We analyzed the SKNA and ablation outcomes in the different energy settings., Results: Both groups had a similar baseline average SKNA (aSKNA). We found that the median aSKNA increased significantly from 446.82 μV to 805.93 μV (p = 0.003) in the ConV group but not in the HPSD group. In the ConV group, patients without AF recurrence had higher aSKNA values. However, the 1-year AF recurrence rate remained similar between both groups (35 % vs. 28 %, p = 0.52)., Conclusion: The post-ablation aSKNA levels increased significantly in the ConV group but did not change significantly in the HPSD group, which may reflect different neuromodulatory effects. However, the one-year AF recurrence rates were similar for both groups. These results demonstrate that the HPSD strategy has durable lesion creation but less lesion depth, which may reduce collateral damage., Competing Interests: Declaration of competing interest None., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: The effects of sedative and anesthetic agents on sympathetic nerve activity (SNA) are poorly understood.Objective: The purpose of this study was to determine the effects of commonly used sedative and anesthetic agents on SNA in ambulatory dogs and humans.Methods: We implanted radiotransmitters in 6 dogs to record stellate ganglion nerve activity (SGNA), subcutaneous nerve activity (ScNA), and blood pressure (BP). After recovery, we injected dexmedetomidine (3 μg/kg), morphine (0.1 mg/kg), hydromorphone (0.05 mg/kg), and midazolam (0.1 mg/kg) on different days. We also studied 12 human patients (10 male; age 68.0 ± 9.1 years old) undergoing cardioversion for atrial fibrillation with propofol (0.77 ± 0.18 mg/kg) or methohexital (0.65 mg/kg) anesthesia. Skin sympathetic nerve activity (SKNA) and electrocardiogram were recorded during the study.Results: SGNA and ScNA were significantly suppressed immediately after administration of dexmedetomidine (P = .000 and P = .000, respectively), morphine (P = .011 and P = .014, respectively), and hydromorphone (P = .000 and P = .012, respectively), along with decreased BP and heart rate (HR) (P <.001 for each). Midazolam had no significant effect on SGNA and ScNA (P = .248 and P = .149, respectively) but increased HR (P = .015) and decreased BP (P = .004) in ambulatory dogs. In patients undergoing cardioversion, bolus propofol administration significantly suppressed SKNA (from 1.11 ± 0.25 μV to 0.77 ± 0.15 μV; P = .001), and the effects lasted for at least 10 minutes after the final cardioversion shock. Methohexital decreased chest SKNA from 1.59 ± 0.45 μV to 1.22 ± 0.58 μV (P = .000) and arm SKNA from 0.76 ± 0.43 μV to 0.55 ± 0.07 μV (P = .001). The effects lasted for at least 10 minutes after the cardioversion shock.Conclusion: Propofol, methohexital, dexmedetomidine, morphine, and hydromorphone suppressed, but midazolam had no significant effects on, SNA. [ABSTRACT FROM AUTHOR]

Background: Heightened sympathetic nerve activity is associated with occurrence of ventricular arrhythmia (VA).Objective: To investigate the association of skin sympathetic nerve activity (SKNA) and VA occurrence.Methods: We prospectively enrolled 65 patients with severe cardiomyopathy. Of these, 39 had recent sustained VA episodes (VA-1 group), 11 had intractable VA undergoing sedation with general anesthesia (VA-2 group), and 15 had no known history of VA (VA-Ctrl group). All patients had simultaneous SKNA and electrocardiogram recording. SKNA was assessed using an average value (aSKNA), a variable value (vSKNA), and the number of bursts of SKNA (bSKNA).Results: The VA-1 group had higher aSKNA and vSKNA compared with the VA-Ctrl group (aSKNA: 1.41 ± 0.53 μV vs 0.98 ± 0.41 μV, P = .003; vSKNA: 0.52 ± 0.22 μV vs 0.30 ± 0.16 μV, P < .001) and the VA-2 group (aSKNA: 0.83 ± 0.22 μV, P < .001; vSKNA: 0.23 ± 0.11 μV; P < .001). Although the VA-2 group had more VA episodes than the VA-1 group (median, 5 vs 2; P = .01), their SKNA was the lowest among the 3 groups. Multivariate Cox regression analysis showed that a higher aSKNA at baseline was an independent predictor of lower VA recurrence rate during a 417 ± 279-day follow-up (hazard ratio, 0.325; 95% confidence interval [CI], 0.119-0.883; P = .03). A >15% reduction in aSKNA after therapy was associated with a lower subsequent VA event rate (hazard ratio, 0.222; 95% CI, 0.057-0.864; P = .03).Conclusion: Patients with VA had increased SKNA as compared with control. Both SKNA and sustained VA could be suppressed by general anesthesia. The aSKNA at baseline was an independent predictor of VA recurrence. [ABSTRACT FROM AUTHOR]

We review the existence of vestibulosympathetic reflexes in humans. While several methods to activate the human vestibular apparatus have been used, galvanic vestibular stimulation (GVS) is a means of selectively modulating vestibular afferent activity via electrodes over the mastoid processes, causing robust vestibular illusions of side-to-side movement. Sinusoidal GVS (sGVS) causes partial entrainment of sympathetic outflow to muscle and skin. Modulation of muscle sympathetic nerve activity (MSNA) from vestibular inputs competes with baroreceptor inputs, with stronger temporal coupling to the vestibular stimulus being observed at frequencies remote from the cardiac frequency; “super entrainment” was observed in some individuals. Low-frequency (

The skin is an accessible model circulation for studying vascular function and dysfunction across the lifespan. Age-related changes, as well as those associated with disease progression, often appear first in the cutaneous circulation. Furthermore, impaired vascular signaling and attendant endothelial dysfunction, the earliest indicators of cardiovascular pathogenesis, occur in a similar fashion across multiple tissue beds throughout the body, including the skin. Because microvascular dysfunction is a better predictor of long-term outcomes and adverse cardiovascular events than is large vessel disease, an understanding of age-associated changes in the control of the human cutaneous microcirculation is important. This review focuses on 1) the merits of using skin-specific methods and techniques to study vascular function, 2) microvascular changes in aged skin (in particular, the role of the endothelial-derived dilator nitric oxide), and 3) the impact of aging on heat-induced changes in skin vasodilation. While skin blood flow is controlled by multiple, often redundant, mechanisms, our laboratory has used a variety of distinct thermal provocations of this model circulation to isolate specific age-associated changes in vascular function. Skinspecific approaches and techniques, such as intradermal microdialysis coupled with laser-Doppler flowmetry (in vivo) and biochemical analyses of skin biopsy samples (in vitro), have allowed for the targeted pharmacodissection of the mechanistic pathways controlling skin vasoreactivity and study of the impact of aging and disease states. Aged skin has an attenuated ability to vasodilate in response to warm stimuli and to vasoconstrict in response to cold stimuli. [ABSTRACT FROM AUTHOR]

We review the existence of vestibulosympathetic reflexes in humans. While several methods to activate the human vestibular apparatus have been used, galvanic vestibular stimulation (GVS) is a means of selectively modulating vestibular afferent activity via electrodes over the mastoid processes, causing robust vestibular illusions of side-to-side movement. Sinusoidal GVS (sGVS) causes partial entrainment of sympathetic outflow to muscle and skin. Modulation of muscle sympathetic nerve activity (MSNA) from vestibular inputs competes with baroreceptor inputs, with stronger temporal coupling to the vestibular stimulus being observed at frequencies remote from the cardiac frequency; "super entrainment" was observed in some individuals. Low-frequency (<0.2 Hz) sGVS revealed two peaks of modulation per cycle, with bilateral recordings of MSNA or skin sympathetic nerve activity, providing evidence of lateralization of sympathetic outflow during vestibular stimulation. However, it should be noted that GVS influences the firing of afferents from the entire vestibular apparatus, including the semicircular canals. To identify the specific source of vestibular input responsible for the generation of vestibulosympathetic reflexes, we used low-frequency (<0.2 Hz) sinusoidal linear acceleration of seated or supine subjects to, respectively, target the utricular or saccular components of the otoliths. While others had discounted the semicircular canals, we showed that the contributions of the utricle and saccule to the vestibular modulation of MSNA are very similar. Moreover, that modulation of MSNA occurs at accelerations well below levels at which subjects are able to perceive any motion indicates that, like vestibulospinal control of posture, the vestibular system contributes to the control of blood pressure through potent reflexes in humans. [ABSTRACT FROM AUTHOR]

Thermal stress is a profound sympathetic stress in humans; kidney responses involve altered renal sympathetic nerve activity (RSNA), renal blood flow, and renal epithelial transport. During mild cold stress, RSNA spectral power but not total activity is altered, renal blood flow is maintained or decreased, and epithelial transport is altered consistent with a sympathetic stress coupled with central volume loaded state. Hypothermia decreases RSNA, renal blood flow, and epithelial transport. During mild heat stress, RSNA is increased, renal blood flow is decreased, and epithelial transport is increased consistent with a sympathetic stress coupled with a central volume unloaded state. Hyperthermia extends these directional changes, until heat illness results. Because kidney responses are very difficult to study in humans in vivo , this review describes and qualitatively evaluates an in vivo human skin model of sympathetically regulated epithelial tissue compared to that of the nephron. This model utilizes skin responses to thermal stress, involving 1) increased skin sympathetic nerve activity (SSNA), decreased skin blood flow, and suppressed eccrine epithelial transport during cold stress; and 2) increased SSNA, skin blood flow, and eccrine epithelial transport during heat stress. This model appears to mimic aspects of the renal responses. Investigations of skin responses, which parallel certain renal responses, may aid understanding of epithelial-sympathetic nervous system interactions during cold and heat stress. [ABSTRACT FROM AUTHOR]

The autonomic nervous system plays a vital role in cardiac arrhythmias, including atrial fibrillation (AF). Therefore, reducing the sympathetic tone via neuromodulation methods may be helpful in AF control. Myocardial ischemia is associated with increased sympathetic tone and incidence of AF. It is an excellent disease model to understand the neural mechanisms of AF and the effects of neuromodulation. This review summarizes the relationship between autonomic nervous system and AF and reviews methods and mechanisms of neuromodulation. This review proposes that noninvasive or minimally invasive neuromodulation methods will be most useful in the future management of AF., Competing Interests: This study was supported in part by the Ministry of Science and Technology, Taiwan (grant MOST 110-2314-B-037-111), the Kaohsiung Medical University Hospital Research Foundation (grants SI11001, SI11101, KMUH105-5M07, KMUH-S10707, and NK111P24), the US National Institutes of Health (grants R01HL139829 and OT2OD028190), and the Burns and Allen Chair in Cardiology Research, Cedars-Sinai Medical Center, Los Angeles, California. Dr Peng-Sheng Chen and Lan S. Chen are co-inventors of U.S. Patents awarded to Indiana University. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2023 The Authors.)

We recorded skin sympathetic nerve activity (SSNA), SSR, and SVR in 30 subjects. SSNA and SVR showed a slight decrease and spontaneous changes in resting SSR were significantly less frequent in older subjects compared with younger subjects ( p < 0.05). There was no significant relationship between age and the reflex latency or amplitude of SSNA, SSR, and SVR in response to electrical stimulation. [ABSTRACT FROM AUTHOR]

Acute pain triggers adaptive physiological responses that serve as protective mechanisms that prevent continuing damage to tissues and cause the individual to react to remove or escape the painful stimulus. However, an extension of the pain response beyond signaling tissue damage and healing, such as in chronic pain states, serves no particular biological function; it is maladaptive. The increasing number of chronic pain sufferers is concerning, and the associated disease burden is putting healthcare systems around the world under significant pressure. The incapacitating effects of long-lasting pain are not just psychological - reflexes driven by nociceptors during the establishment of chronic pain may cause serious physiological consequences on regulation of other body systems. The sympathetic nervous system is inherently involved in a host of physiological responses evoked by noxious stimulation. Experimental animal and human models demonstrate a diverse array of heterogeneous reactions to nociception. The purpose of this review is to understand how pain affects the sympathetic nervous system by investigating the reflex cardiovascular and neural responses to acute pain and the long-lasting physiological responses to prolonged (tonic) pain. By observing the sympathetic responses to long-lasting pain, we can begin to understand the physiological consequences of long-term pain on cardiovascular regulation. [ABSTRACT FROM AUTHOR]