Sympathetic Nerve Activity In Patients Research Articles

Remote ischemic peri-conditioning suppressed cardiac sympathetic nerve activity especially in the non-culprit lesion in patients with acute myocardial infarction

Abstract Background Remote ischemic periconditioning (RIPC) has demonstrated cardioprotective effects and improved clinical outcomes as an adjunct to emergent percutaneous coronary intervention (PCI) in patients with acute myocardial infarction (AMI). However, it remains to be elucidated whether RIPC affects the cardiac sympathetic nerve activity in patients with AMI. Purpose The purpose of this study is to investigate the effect of RIPC on cardiac sympathetic nerve activity (CSNA) in the culprit and non-culprit lesion respectively in patients with AMI. Methods We randomly assigned 157 patients with suspected AMI undergoing emergent PCI to receive transient limb ischemia (by inflating a cuff at 200 mmHg for 4×5 minutes: RIPC group, n=77) or no procedure (control group, n=80). After excluding inappropriate patients such as those with other diagnosis than AMI, we analyzed 122 patients (62 patients in RIPC and 60 in control group). CSNA was assessed in the culprit and non-culprit lesion respectively by the cardiac MIBG SPECT imaging. Results Patients in RIPC and control group had similar demographic and clinical characteristics at baseline. Patients in RIPC group tended to show higher late uptake only in the non-culprit lesion at discharge. At 1 year after discharge, patients in RIPC group demonstrated significantly higher late uptake (p=0.021) and lower washout rate (p=0.013) than those in control group in the non-culprit lesion. Regarding the culprit lesion, only washout rate tended to be lower in RIPC group at 1 year after discharge. Conclusion(s): Remote ischemic peri-conditioning showed suppressive effect on cardiac sympathetic nerve activity especially in the non-culprit lesion in patients with acute myocardial infarction.SPECT parameters in RIPC and control

Remote ischemic periconditioning suppresses cardiac sympathetic activation in acute myocardial infarction: a randomized controlled trial.

Remote ischemic periconditioning (RIPC) has demonstrated cardioprotective effects and improved clinical outcomes as an adjunct to emergent percutaneous coronary intervention (PCI) in patients with ST-elevation myocardial infarction (STEMI). However, whether RIPC affects the cardiac sympathetic nerve activity in patients with STEMI remains unclear. This study investigated the effects of RIPC on cardiac sympathetic nerve activity in patients with STEMI. We prospectively assigned patients with STEMI who underwent emergent PCI to receive RIPC or no procedure (control group) upon arrival at the cardiac catheterization laboratory. The primary endpoint was cardiac sympathetic nerve activity assessed through the washout rate (WR) in cardiac 123I-metaiodobenzylguanidine (123I-MIBG) imaging. Patients in the RIPC (n = 62) and control (n = 60) groups had similar demographic and clinical characteristics at baseline. Multivariable linear regression models revealed that the culprit lesion of the left anterior descending artery and hemoglobin level were significantly and independently associated with WR at discharge. WRs of the groups differed insignificantly at discharge. However, the RIPC group (n = 49) showed significantly lower WR than the control group (n = 47) at 1year after discharge (p = 0.027). In the single-photon emission computed tomography analysis at 1year after discharge, the RIPC group demonstrated significantly higher late uptake (p = 0.021) and lower WR (p = 0.013) in the nonculprit lesion, with a non-significant decrease in WR for the culprit lesion. RIPC can suppress augmented cardiac sympathetic nerve activity in patients with STEMI, particularly in nonculprit lesions.

Characterization of skin sympathetic nerve activity in patients undergoing ablation of ventricular tachycardia

Characterization of skin sympathetic nerve activity in patients undergoing ablation of ventricular tachycardia

5-Aminolevulinic acid hydrochloride enhances bupivacaine-induced hypotension in spontaneously hypertensive rats

PurposeOral administration of 5-aminolevulinic acid hydrochloride (5-ALA-HCl) has been reported to enhance the hypotensive effects associated with anesthetics, especially in elderly hypertensive patients treated with antihypertensive agents. The present study aimed to clarify the effects of antihypertensive-agent- and anesthesia-induced hypotension by 5-ALA-HCl in spontaneously hypertensive rats (SHRs). MethodsWe measured blood pressure (BP) of SHRs and normotensive Wistar Kyoto (WKY) rats treated with amlodipine or candesartan before and after administration of 5-ALA-HCl. We also investigated the change in BP following intravenous infusion of propofol and intrathecal injection of bupivacaine in relation to 5-ALA-HCl administration. FindingsOral administration of 5-ALA-HCl significantly reduced BP in SHRs and WKY rats with amlodipine and candesartan. Infusion of propofol significantly reduced BP in SHRs treated with 5-ALA-HCl. Intrathecal injection of bupivacaine significantly declined SBP and DBP in both SHRs and WKY rats treated with 5-ALA-HCl. The bupivacaine-induced decline in SBP was significantly larger in SHRs compared with WKY rats. ConclusionThese findings suggest that 5-ALA-HCl does not affect the antihypertensive agents-induced hypotensive effect, but enhances the bupivacaine-induced hypotensive effect, especially in SHRs, indicating that 5-ALA may contribute to anesthesia-induced hypotension via suppression of sympathetic nerve activity in patients with hypertension.

Carotid Artery Revascularization Improves Cardiac Sympathetic Nerve Activity in Patients With Carotid Artery Stenosis.

The carotid sinus baroreceptor reflex controls the neural regulation of blood pressure. Baroreceptor disorders due to carotid sinus atherosclerosis have detrimental cardiovascular effects. This study investigated the medium-term effects of carotid artery revascularization (CAR) on sympathetic and cardiac function and systemic blood pressure variability in patients with carotid artery stenosis. This study included 21 consecutive patients (median age 70 years, 18 men) with carotid artery stenosis scheduled for CAR. 123I metaiodobenzylguanidine (MIBG) scintigraphy, echocardiography, brain natriuretic peptide levels, 24-h Holter electrocardiography (ECG), and ambulatory blood pressure monitoring assessed approximately 3 months postoperatively were compared to preoperative data. All 21 enrolled patients underwent CAR. Carotid artery stenting was done in three patients with cardiovascular risk or anatomical difficult for carotid endarterectomy. The mean common carotid artery end-diastolic velocity improved significantly (P < 0.01) by 1.6-fold, from 10.8 ± 3.2 to 16.1 ± 7.1 cm/s. In 123I-MIBG scintigraphy, the heart-to-mediastinum (H/M) count ratio was significantly higher than preoperatively (from 2.66 ± 0.48 to 2.86 ± 0.56, P = 0.03). Holter ECG analysis revealed a significant decrease in the low-frequency/high-frequency (LF/HF) ratio compared to preoperatively (from 2.17 ± 1.20 to 1.62 ± 0.68, P = 0.04). These findings suggest decreased myocardial sympathetic activation. In echocardiography, the tissue Doppler-derived e' increased, and E/e' decreased significantly (P < 0.05) from 11.7 ± 5.1 to 10.1 ± 4.0, suggesting an improved left ventricular diastolic capacity. The mean 24-h and nighttime blood pressures were unchanged. CAR in patients with carotid stenosis may provide medium-term improvement in cardiac sympathetic nerve activity and left ventricular diastolic dysfunction.

Skin sympathetic nerve activity in patients with chronic orthostatic intolerance.

Chronic orthostatic intolerance (OI) is characterizedby the development of tachycardia and other symptomswhen assuming an upright body position. The purpose of this study was to test the hypothesis that skin sympathetic nerve activity (SKNA) bursts are specific symptomatic biomarkers in patients with chronic OI. We used an electrocardiogram monitor with a built-in triaxial accelerometer to simultaneously record SKNA and posture in ambulatory participants. Study 1 compared chronic OI (14 women and 2 men; mean age 35 ± 10 years) with reference control participants (14 women; mean age 31 ± 6 years). Study 2 included 17 participants with chronic OI (15 women and 2 men; mean age 39 ± 12 years) not yet treated with ivabradine, pyridostigmine, or β-blockers. In study 1, there were 124 episodes (8 ± 4 per participant) of postural changes, with 11 episodes (8.9%) associated with symptoms. In comparison, 0 of 104 postural changes (7 ± 3 per participant) in controls were symptomatic (P = .0011). In participants with chronic OI, the SKNA bursts associated with symptomshad higher burst frequencies, longer burst durations, and larger mean burst areas than did bursts during asymptomatic periods. However, SKNA bursts and tachycardia were asymptomaticin controls. We analyzed 110 symptomatic episodes in study 2 (6 ± 5 per participant). Among them, 98 (89.1%) followed at least 1 SKNA burst. In comparison, only 41 (37.3%) had heart rate exceed 100 beats/min 1 minute before symptom onset (P < .0001). SKNA bursts are a highly specific, albeit insensitive, symptomatic biomarker for chronic OI.

Effect of pulmonary vein isolation on the relationship between left atrial reverse remodeling and sympathetic nerve activity in patients with atrial fibrillation.

Catheter ablation (CA) to isolate the pulmonary vein, which is an established treatment for atrial fibrillation (AF), is associated with left atrium reverse remodeling (LARR). The intrinsic cardiac autonomic nervous system includes the ganglion plexi adjacent to the pulmonary vein in the left atrium (LA). However, little is known about the effect of CA on the relationship between LARR and sympathetic nerve activity in patients with AF. This study enrolled 22 AF patients with a normal left ventricular ejection fraction (LVEF) aged 64.6 ± 12.9years who were scheduled for CA. Sympathetic nerve activity was evaluated by direct recording of muscle sympathetic nerve activity (MSNA) before and 12weeks after CA. Blood pressure, heart rate (HR), HR variability, and echocardiography were also measured. The heart rate increased significantly after CA (63 ± 10.9 vs. 70.6 ± 7.7 beats/min, p < 0.01), but blood pressure did not change. A high frequency (HF) and low frequency (LF) of HR variability decreased significantly after ablation, but no significant change in LF/HF was observed. CA significantly decreased MSNA (38.9 ± 9.9 vs. 28 ± 9.1 bursts/min, p < 0.01). Moreover, regression analysis revealed a positive correlation between the percentage change in MSNA and the LA volume index (r = 0.442, p < 0.05). Our results show that CA for AF reduced MSNA and the decrease was associated with the LA volume index in AF patients with a normal LVEF. These findings suggest that LARR induced by CA for AF decrease sympathetic nerve activity.

Implications of sympathetic activation for objective versus self-reported daytime sleepiness in obstructive sleep apnea.

Objective excessive daytime sleepiness (EDS) is associated with systemic inflammation and a higher risk of cardiometabolic morbidity in obstructive sleep apnea (OSA). We hypothesized that OSA with objective EDS is associated with higher levels of sympathetic nerve activity (SNA) when compared with self-reported EDS. We, therefore, examined the associations between objective and self-reported EDS with SNA in patients with OSA. We studied 147 consecutive male patients with OSA from the institutional sleep clinic. Objective EDS and self-reported EDS were defined based on Multiple Sleep Latency Test (MSLT) latency ≤ 8 minutes and Epworth Sleepiness Scale (ESS) > 10, respectively. Twenty-four-hour urinary norepinephrine was used for assessing SNA. Blood pressure (BP) was measured both in the evening and in the morning. Twenty-four-hour urinary norepinephrine was significantly higher in patients with OSA with objective EDS compared with those without objective EDS (p = 0.034), whereas it was lower in patients with OSA with self-reported EDS compared with those without self-reported EDS (p = 0.038) after adjusting for confounders. Differences in the sympathetic drive were most striking in those with an objective but not self-reported EDS versus those with self-reported but not objective EDS (p = 0.002). Moreover, shorter MSLT latency was significantly associated with higher diastolic BP (β = -0.156, p = 0.049) but not systolic BP. No significant association between ESS scores and BP was observed. Objective, but not self-reported EDS, is associated with increased SNA and diastolic BP among males with OSA, suggesting that objective EDS is a more severe phenotype of OSA that is accompanied by higher sympathetic drive, higher BP, and possibly greater cardiovascular morbidity and mortality.

Successful continuous positive airway pressure treatment reduces skin sympathetic nerve activity in patients with obstructive sleep apnea.

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). The purpose of this study was to test the hypothesis that continuous positive airway pressure (CPAP) treatment reduces SKNA. 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. 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. 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.

High Skin Sympathetic Nerve Activity in Patients with Recurrent Syncope.

(1) Background: The autonomic imbalance plays a role in vasovagal syncope (VVS) diagnosed by head-up tilting test (HUT). neuECG is a new method of recording skin electrical signals to simultaneously analyze skin sympathetic nerve activity (SKNA) and electrocardiogram. We hypothesize that SKNA is higher in subjects with tilt-positive than tilt-negative and the SKNA surges before syncope. (2) Methods: We recorded neuECG in 41 subjects who received HUT (according to the “Italian protocol”), including rest, tilt-up, provocation and recovery phases. Data were analyzed to determine the average SKNA (aSKNA, μV) per digitized sample. Electrocardiogram was used to calculate standard deviation of normal-to-normal beat intervals (SDNN). The “SKNA-SDNN index” was calculated by rest aSKNA multiplied by the ratio of tilt-up to rest SDNN. (3) Results: 16 of 41 (39%) subjects developed syncope. The aSKNA at rest phase is significantly higher in the tilt-positive (1.21 ± 0.27 µV) than tilt-negative subjects (1.02 ± 0.29 µV) (p = 0.034). There are significant surges and withdraw of aSKNA 30 s before and after syncope (both p ≤ 0.006). SKNA-SDNN index is able to predict syncope (p < 0.001). (4) Conclusion: Higher SKNA at rest phase is associated with positive HUT. The SKNA-SDNN index is a novel marker to predict syncope during HUT.

Effect of pulmonary vein isolation on left atrial remodeling and muscle sympathetic nerve activity in patients with atrial fibrillation

Abstract Background Catheter ablation (CA) for atrial fibrillation (AF) improves left ventricular function and induces left atrium reverse remodeling (LARR). CA is also associated with the modulation of ganglionated plexi in the left atrium (LA), including stretch-sensitive sympathetic and parasympathetic nerve mechanoreceptors. Increased filling pressure and enlargement of LA stimulate stretch-sensitive sympathetic nerve mechanoreceptors in heart failure, which contribute augmented sympathetic nerve activity. However, little is known about an effect of CA on the interaction between the changes of LARR and sympathetic nerve activity. Purpose To test the hypothesis that CA induce the reduction in sympathetic nerve activity in accordance with LARR in patients with atrial fibrillation. Methods This study was conducted as a retrospective, observational study. Twenty-eight AF patients (65.4±12.1 years old) were included in this study. We measured mean blood pressure (BP), heart rate (HR), brain natriuretic peptide (BNP), and direct recording of muscle sympathetic nerve activity (MSNA) using microneurography technique before and 12 weeks after CA. Echocardiogram was also performed to assess LARR and left ventricular function. To evaluate the interaction between LARR and MSNA, AF patients were divided into two groups by presence (LARR group; n=18) and absence (no LARR group; n=10) of LARR according to left atrium volume index (LAVi) following CA. Results No significant differences were observed at baseline in BP, MSNA and LAVi between two groups. BP did not change significantly after CA in both groups. HR significantly increased in the LARR group (63.1±5.7 vs 69.9±7.8, p&amp;lt;0.01) compared to no LARR group. CA significantly reduced MSNA in the LARR group (37.8±10.1 vs 24.9±8.8 bursts/min, p&amp;lt;0.01), but there was no significant change in the no LARR group. The septal E/e' ratio (11.3±3.8 vs 9.8±2.9, p&amp;lt;0.05), left ventricular end-systolic volume index (LVESVi) (24.4±11.9 vs 19.6±7.8 ml/m2, p&amp;lt;0.05) and Ln BNP (4.0±1.2 vs 3.3±1.0 log/pg/ml, p&amp;lt;0.05) were also significantly improved in the LARR group. On the other hand, in the no LARR group, there were no significancy in the changes of the septal E/e' ratio, LVESVi and Ln BNP. LVEF was not significantly changed in both two groups. Conclusion Our study shows CA reduced MSNA accompanied by LARR in AF patients. The reduction in MSNA, septal E/e' ratio, LVESVi and Ln BNP were all more pronounced in the LARR group compared to the no LARR group. These findings suggest that LARR is associated with the reduction in MSNA in AF patients, which was attributed to CA-induced modulation of stretch-sensitive sympathetic nerve mechanoreceptors. Funding Acknowledgement Type of funding sources: None.

Sympathetic Nerve Activity During Tooth Extraction in Women Is Related to Dental Anxiety Immediately After Surgery

This study assessed the relationship between changes in autonomic nervous system activity during impacted mandibular third molar extraction and a patient's postoperative psychological status, with the overarching aim of informing the development of interventions to reduce dental phobia and anxiety. We hypothesized that changes in autonomic nervous system activity during tooth extraction are related to postoperative psychology. In our prospective cohort study, heart rate variability, heart rate (HR), and systolic blood pressure (SBP) were recorded during impacted mandibular third molar extraction. Heart rate variability values were dichotomized as either low frequency (LF 0.04-0.15 Hz) or high frequency (HF >0.15 Hz). The relative ratios (intraoperative vs baseline) of LF/HF, HF, HR, and SBP were divided into high and low groups based on their median values; the State Anxiety Inventory (STAI-S) results were compared between the groups with high and low relative ratios. Data of 34 female patients (age, 28.23 ± 1.05 years) were analyzed. Postoperative STAI-S values were significantly lower than preoperative values. Patients in the high LF/HF group had a significantly lower change in STAI-S values than those in the low LF/HF group (P < .05). There were no significant differences in the change in STAI-S values between the groups with high and low HF, HR, or SBP. Patients with low sympathetic nervous system activity had lower anxiety; the LF/HF index was the most sensitive indicator for changes in stress. Additional studies are required to develop optimal interventions for reducing sympathetic nerve activity in patients with dental phobia.

Abstract 16157: Catheter Ablation Induces an Increase in Heart Rate With Discordant With a Decrease in Sympathetic Nerve Activity in Patients With Paroxysmal Atrial Fibrillation

Background/Introduction: Paroxysmal atrial fibrillation (PAF) is the most common arrhythmia and catheter ablation (CA) is selected with the aim of rhythm control. CA was reported to increase heart rate (HR), which explains the modulation on the cardiac autonomic nervous system. However, little is known about the relationship between heart rate, sympathetic nerve activity and parasympathetic nerve activity in patient with PAF. Purpose: The purpose of this study was to evaluate the effect of CA on direct recording of muscle sympathetic nerve activity (MSNA) and heart rate variability (HRV), and these influences on HR. Methods: This study was conducted as a prospective, observational study. Patients with PAF who were scheduled for CA were enrolled. We measured blood pressure, HR, body weight, brain natriuretic peptide (BNP), echocardiogram parameters, high frequency component as cardiac parasympathetic nerve activity and low frequency component as cardiac sympathetic nerve activity in HRV, and MSNA before and 12 weeks after CA. Results: 21 PAF patients participated in this study. After CA, E/e’ and Ln BNP were significantly reduced(10.6±2.9 to 9.2±2.6, p&lt;0.05. 3.8±1.3 to 3.3±1.6 log/pg/ml, p&lt;0.05, respectively) while no significant changes were observed in EF, SV, left atrial diameter, left ventricular end diastolic and systolic diameters. HR was significantly increased (61.3±7.8 to 71.1±7.6 beats/min, p&lt;0.05, respectively). However, the MSNA burst incidence and frequency were significantly decreased (65.4±12.6 to 41.3±13.4 bursts/100beats, p&lt;0.01, n=21. 39.8±8.8 to 28.1±9.6 bursts/min, p&lt;0.01, n=21. respectively). Also, the reduction in MSNA burst frequency was correlated with the increase in HR (r=0.57, 95%CI 0.183-0.804, p=0.00702). Ln Low frequency component in HRV was significantly decreased (5.72±1.75 to 3.85±2.13 log/ms 2 , p&lt;0.05, n=12), but Ln high frequency (HF) component was not changed . No significant relationship observed between increased HR and HF component. Conclusion: CA induced paradoxical increasing heart rate with the reduction in sympathetic nerve activity in patient with PAF. These findings suggest that CA might modulate autonomic interaction between sinus nodes and in left atrium with denervated in ganglionated plexi.

Abstract 16604: Significant Correlation Between Arterial Velocity Pulse Index and Muscle Sympathetic Nerve Activity in Hypertensive Patients

Introduction: Augmented sympathetic nerve activity (SNA) in hypertension (HT) is regarded as a therapeutic target, but there is few non-invasive markers to evaluate SNA in clinical practice. It is reported to associate with SNA which increased arterial reflected wave plays the important role in disease progression in HT, and it is reported to associate with SNA. Recently, Arterial Velocity Pulse Index (AVI) are developed as an index of arterial reflected waves, however the relationship between AVI and SNA is still uncertain. Methods: Patients with essential HT and matched non-hypertensive control subjects were included in this study. HT was diagnosed as systolic blood pressure (SBP) ≧ 140 mmHg or diastolic blood pressure (DBP) ≧ 90 mmHg. Patients with secondary HT was excluded. AVI was measured from left upper arm by NAS-1000 (Nihon Koden, Japan). SNA was evaluated by direct recording of muscle sympathetic nerve activity (MSNA) from peroneal nerves. Results: 50 HT patients and 50 control subjects were included. Age, SBP and DBP were significantly increased in HT group compared to control (Age 63±14 vs 42±16 years, p&lt;0.001; SBP 144±16 vs 115±9 mmHg, p&lt;0.001; DBP 80±14 vs 67±9 mmHg, p&lt;0.001). MSNA and AVI were significantly increased in HT group compared to control (MSNA 34±10 vs 25±8 bursts/min, p&lt;0.05; AVI 28±9 vs 17±5, p&lt;0.05). In univariate analysis, AVI was significantly correlated with MSNA, age, and SBP in HT group. However, no significant relationship was observed between AVI and MSNA in multivariate analysis. Therefore, HT group was divided into two groups according to their severity (group 1, SBP&lt;160mmHg, N=30; group 2, SBP&gt;160 mmHg, N=20). AVI in group 1 showed significantly correlation with MSNA (r=0.49, p&lt;0.05), but no correlation was seen in group 2. Conclusions: AVI was significantly increased in patients with HT compared to control, and AVI is significantly associated with MSNA in HT patients with SBP&lt;160mmHg. These results indicate that AVI is helpful to estimate augmented SNA in patients with mild or moderate hypertension. Further study is warranted to exam the relationship AVI and SNA in reality.

Nocturnal blood pressure is associated with sympathetic nerve activity in patients with chronic kidney disease.

Elevated nocturnal blood pressure (BP) and nocturnal non‐dipping are frequently observed in patients with chronic kidney disease (CKD) and are stronger predictors of cardiovascular complications and CKD progression than standard office BP. The sympathetic nervous system (SNS) is thought to modulate diurnal hemodynamic changes and the vascular endothelium plays a fundamental role in BP regulation. We hypothesized that SNS overactivity and endothelial dysfunction in CKD are linked to elevated nocturnal BP and non‐dipping. In 32 CKD patients with hypertension (56 ± 7 years), office BP, 24‐hr ambulatory BP, muscle sympathetic nerve activity (MSNA) and endothelial function via flow‐mediated dilation (FMD) were measured. Participants were subsequently divided into dippers (nighttime average BP > 10% lower than the daytime average BP, n = 8) and non‐dippers (n = 24). Non‐dippers had higher nighttime BP (p < .05), but not office and daytime BP, compared to dippers. MSNA burst incidence (81 ± 13 versus 67 ± 13 bursts/100 HR, p = .019) was higher and brachial artery FMD (1.7 ± 1.5 versus 4.7 ± 1.9%, p < .001) was lower in non‐dippers compared to dippers. MSNA and FMD each predicted nighttime systolic (β = 0.48,‐0.46, p = .02, 0.07, respectively) and diastolic BP (β = 0.38,‐0.47, p = .04, 0.03, respectively) in multivariate‐adjusted analyses. Our novel findings demonstrate that unfavorable nocturnal BP profiles are associated with elevated SNS activity and endothelial dysfunction in CKD. Specifically, CKD patients with higher nighttime BP and the non‐dipping pattern have higher MSNA and lower FMD. These support our hypothesis that SNS overactivation and endothelial dysfunction are linked to the dysregulation of nighttime BP as well as the magnitude of BP lowering at nighttime in CKD.

Skin sympathetic nerve activity in patients with obstructive sleep apnea

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). 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. 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. 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). 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.

Left cardiac sympathetic denervation reduces skin sympathetic nerve activity in patients with long QT syndrome

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. The purpose of this study was to assess skin sympathetic nerve activity (SKNA) in patients with LQTS undergoing LCSD. 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. 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. LCSD provides an inhibitory effect on cardiac sympathetic activity by suppressing burst discharge as measured by SKNA.

P3559Renal sympathetic nerve activity, assessed by renal 123-iodine metaiodobenzylguanidine scintigraphy, reflects disease severity in heart failure with reduced ejection fraction

Abstract Background Sympathetic nerve activity is related to cardio-renal syndrome, which plays a crucial role in deterioration in heart failure with reduced ejection fraction (HFrEF). Previous studies reported that renal denervation was effective in HFrEF patients. Recently, we have demonstrated that renal 123-iodine metaiodobenzylguanidine (MIBG) scintigraphy is useful for assessment of renal sympathetic function in hypertension. However, it is unclear whether renal MIBG would reflect disease severity in HFrEF patients. Methods Twenty-four HFrEF patients and eleven control without heart failure were included in this study. HFrEF patients were performed MIBG and MSNA and hemodynamics inspection using Swan-Ganz's catheter (SGC). HFrEF was defined as echocardiography with EF of 50% or less. MSNA was recorded from the right peroneal nerve to evaluate direct sympathetic nerve activity to the peripheral vascular bed. MSNA was expressed as the number per minute (burst frequency = BF) and the number per 100 heartbeats (burst incidence = BI). Renal MIBG scintigraphy was simultaneously performed with cardiac MIBG scintigraphy. The 20 minutes (early) and 180 minutes (delayed) kidney-to-mediastinum ratio (K/M), early and delayed heart-to-mediastinum ratio (H/M), and washout rate (WR) were measured. Results In the HFrEF group, the EF was significantly lower than control group (EF 34.8±9.51% vs. 63.0±7.43, p&lt;0.01), and MSNA parameters were significantly increased (burst incidence (BI), 57.7±18.7 vs. 37.0±11.3, p&lt;0.01; BF 42.7±14.4 vs. 24.1±8.50, p&lt;0.01). WR of cardiac MIBG was not related to MSNA parameters but negatively related to cardiac output (r=−0.46, p&lt;0.05) and stroke volume (r=−0.61, p&lt;0.01) and delayed H/M negatively correlated with mean pulmonary capillary wedge pressure (r=−0.57, P&lt;0.05). WR of both left and right renal MIBG showed a strong correlation with MSNA (BI; left, r=0.69, p&lt;0.01, right 0.60, p&lt;0.01, BF; left, r=0.64, p&lt;0.01, right, r=0.58, p&lt;0.01) and no significant correlation between renal MIBG and hemodynamics parameters. HFrEF patients were divided into stage B and stage C based on American College of Cardiology/American Heart Association (ACC/AHA) classification (stage B, n=13; stage C, n=11). There was no significant difference between the two groups in cardiac MIBG parameters. Renal WRs in stage C was increased than stage B (Lt renal WR,51.6±10.6 vs. 40.6±6.53, p&lt;0.05; Rt renal WR, 43.9±9.97 vs. 35.1±11.3, p&lt;0.05). Conclusions Cardiac WR negatively correlated with cardiac output and renal WR correlated with MSNA. Renal WRs had a significant difference in the heart failure stage of ACC/AHA classification, but cardiac MIBG parameters did not. These results indicate that renal MIBG might be useful to assess renal sympathetic nerve activity in patients with HFrEF and suggesting that renal SNA might be promising therapeutic target in HFrEF.

Characterization of skin sympathetic nerve activity in patients with cardiomyopathy and ventricular arrhythmia

Heightened sympathetic nerve activity is associated with occurrence of ventricular arrhythmia (VA). To investigate the association of skin sympathetic nerve activity (SKNA) and VA occurrence. 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). 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). 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.

Renal sympathetic nerve activation via α2-adrenergic receptors in chronic kidney disease progression.

Chronic kidney disease (CKD) is increasing worldwide without an effective therapeutic strategy. Sympathetic nerve activation is implicated in CKD progression, as well as cardiovascular dysfunction. Renal denervation is beneficial for controlling blood pressure (BP) and improving renal function through reduction of sympathetic nerve activity in patients with resistant hypertension and CKD. Sympathetic neurotransmitter norepinephrine (NE) via adrenergic receptor (AR) signaling has been implicated in tissue homeostasis and various disease progressions, including CKD. Increased plasma NE level is a predictor of survival and the incidence of cardiovascular events in patients with end-stage renal disease, as well as future renal injury in subjects with normal BP and renal function. Our recent data demonstrate that NE derived from renal nerves causes renal inflammation and fibrosis progression through alpha-2 adrenergic receptors (α2-AR) in renal fibrosis models independent of BP. Sympathetic nerve activation-associated molecular mechanisms and signals seem to be critical for the development and progression of CKD, but the exact role of sympathetic nerve activation in CKD progression remains undefined. This review explores the current knowledge of NE-α2-AR signaling in renal diseases and offers prospective views on developing therapeutic strategies targeting NE-AR signaling in CKD progression.