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Introduction: Postmenopausal women (PMW) display exaggerated increases in blood pressure (BP) during exercise, yet the mechanism(s) involved remain unclear. Moreover, research on the impact of menopausal changes in estradiol on cardiovascular control during exercise are limited. Herein, we tested the hypothesis that sympathetic responses during exercise are augmented in PMWcompared with young women (YW), and estradiol administration attenuates these responses. Methods : Muscle sympathetic nerve activity (MSNA) and mean arterial pressure (MAP) were measured in 13 PMW (58 +/- 1 yr) and 17 YW (22 +/- 1 yr) during 2 min of isometric handgrip. Separately, MSNA and BP responses were measured during isometric handgrip in six PMW (53 +/- 1 yr) before and after 1 month of transdermal estradiol (100 [mu]g[middle dot]d-1). A period of postexercise ischemia (PEI) to isolate muscle metaboreflex activation followed all handgrip bouts. Results : Resting MAP was similar between PMW and YW, whereas MSNA was greater in PMW (23 +/- 3 vs 8 +/- 1 bursts per minute; P < 0.05). During handgrip, the increases in MSNA (PMW [DELTA]16 +/- 2 vs YW [DELTA]6 +/- 1 bursts per minute; P < 0.05) and MAP (PMW [DELTA]18 +/- 2 vs YW [DELTA]12 +/- 2 mm Hg; P < 0.05) were greater in PMW and remained augmented during PEI. Estradiol administration decreased resting MAP but not MSNA in PMW. Moreover, MSNA (PMW (-E2) [DELTA]27 +/- 8 bursts per minute versus PMW (+E2) [DELTA]12 +/- 5 bursts per minute; P < 0.05) and MAP ([DELTA]31 +/- 8 mm Hg vs [DELTA]20 +/- 6 mm Hg; P < 0.05) responses during handgrip were attenuated in PMW after estradiol administration. Likewise, MAP responses during PEI were lower after estradiol. Conclusions : These data suggest that PMW exhibit an exaggerated MSNA and BP response to isometric exercise, due in part to heightened metaboreflex activation. Furthermore, estradiol administration attenuated BP and MSNA responses to exercise in PMW. [ABSTRACT FROM AUTHOR]

Purpose: Larger blood pressure (BP) responses to relative-intensity static exercise in men versus women are thought to involve altered muscle metaboreflex activation, but whether this is because of an intrinsic sex difference in metabolite production or differences in muscle strength and absolute load is unknown. Methods : Continuous BP and heart rate were recorded in 200 healthy young men and women (women: n = 109) during 2 min of static handgrip exercise at 30% of maximal voluntary contraction (MVC), followed by 2 min of postexercise circulatory occlusion (PECO). Muscle sympathetic nerve activity (MSNA) was recorded in a subset of participants (n = 39; women, n = 21), permitting calculation of signal-averaged resting sympathetic transduction (MSNA-diastolic BP). Sex differences were examined with and without statistical adjustment for MVC. Multivariate regression analyses were performed to identify predictors of BP responses. Results : Men had larger systolic BP responses (interactions, P < 0.0001) to static handgrip exercise (24 +/- 10 vs 17 +/- 9 mm Hg [mean +/- SD], P < 0.0001) and PECO (20 +/- 11 vs 16 +/- 9 mm Hg, P < 0.0001). Adjustment for MVC abolished these sex differences in BP (interactions, P > 0.7). In the subset with MSNA, neither burst frequency or incidence responses to static handgrip exercise or PECO differed between men and women (interactions, P > 0.2). Resting sympathetic transduction was also similar (P = 0.8). Multiple linear regression analysis showed that MVC or the change in MSNA, were predictors of BP responses to static handgrip, but only MVC was associated with BP responses during PECO. Conclusions: Sex differences in absolute contraction load contribute to differences in BP responses during muscle metaboreflex isolation using PECO. These data do not support an intrinsic effect of sex as being responsible for exercise BP differences between men and women. [ABSTRACT FROM AUTHOR]

Introduction: Trauma-induced hemorrhage is a leading cause of death in prehospital settings. Experimental data demonstrate that females have a lower tolerance to simulated hemorrhage (i.e., central hypovolemia). However, the mechanism(s) underpinning these responses are unknown. Therefore, this study aimed to compare autonomic cardiovascular responses during central hypovolemia between the sexes. We hypothesized that females would have a lower tolerance and smaller increase in muscle sympathetic nerve activity (MSNA) to simulated hemorrhage., Methods: Data from 17 females and 19 males, aged 19-45 yr, were retrospectively analyzed. Participants completed a progressive lower-body negative pressure (LBNP) protocol to presyncope to simulate hemorrhagic tolerance with continuous measures of MSNA and beat-to-beat hemodynamic variables. We compared responses at baseline, at two LBNP stages (-40 and -50 mmHg), and at immediately before presyncope. In addition, we compared responses at relative percentages (33%, 66%, and 100%) of hemorrhagic tolerance, calculated via the cumulative stress index (i.e., the sum of the product of time and pressure at each LBNP stage)., Results: Females had lower tolerance to central hypovolemia (female: 561 ± 309 vs male: 894 ± 304 min·mmHg [time·LBNP]; P = 0.003). At LBNP -40 and -50 mmHg, females had lower diastolic blood pressures (main effect of sex: P = 0.010). For the relative LBNP analysis, females exhibited lower MSNA burst frequency (main effect of sex: P = 0.016) accompanied by a lower total vascular conductance (sex: P = 0.028; main effect of sex)., Conclusions: Females have a lower tolerance to central hypovolemia, which was accompanied by lower diastolic blood pressure at -40 and -50 mmHg LBNP. Notably, females had attenuated MSNA responses when assessed as relative LBNP tolerance time., (Copyright © 2024 by the American College of Sports Medicine.)

Purpose: In normotensive patients with obstructive sleep apnea (OSA), the muscle sympathetic nerve activity (MSNA) response to exercise is increased while metaboreflex control of MSNA is decreased. We tested the hypotheses that acute intermittent hypercapnic hypoxia (IHH) in males free from OSA and associated comorbidities would augment the MSNA response to exercise but attenuate the change in MSNA during metaboreflex activation. Methods: Thirteen healthy males (age = 24 ± 4 yr) were exposed to 40 min of IHH. Before and after IHH, the pressor response to exercise was studied during 2 min of isometric handgrip exercise (at 30%maximal voluntary contraction), whereas themetaboreflex was studied during 4min of postexercise circulatory occlusion (PECO).Mean arterial pressure (MAP), heart rate (HR), and fibularMSNA were recorded continuously. MSNA was quantified as burst frequency (BF) and total activity (TA).Mixed effects linear models were used to compare the exercise pressor andmetaboreflex before and after IHH. Results: As expected, IHH led to significant increases in MSNA BF, TA, and MAP at baseline and throughout exercise and PECO. However, during handgrip exercise, the change from baseline inMAP,HR,MSNABF, and TA was similar before and after IHH(All P > 0.31).During PECO, the change from baseline inMSNA BF and TA was similar after IHH, whereas the change from baseline inMAP (Δ14mmHg, 95% CI = 7-19, vs Δ16mmHg, 95% CI = 10-21; P < 0.01) wasmodestly increased. Conclusion: After acute IHH,MSNAresponse to handgrip exercise and metaboreflex activationwere preserved in healthy young males despite overall increases in resting MSNA and MAP. Chronic IHH and comorbidities often associated with OSA may be required to modulate the exercise pressor reflex and metaboreflex. [ABSTRACT FROM AUTHOR]

Background: Neurolytic splanchnic nerve block is used to manage pancreatic cancer pain. However, its impact on survival and quality of life remains controversial. The authors' primary hypothesis was that pain relief would be better with a nerve block. Secondarily, they hypothesized that analgesic use, survival, and quality of life might be affected.Methods: This randomized, double-blind, parallel-armed trial was conducted in five Chinese centers. Eligible patients suffering from moderate to severe pain conditions were randomly assigned to receive splanchnic nerve block with either absolute alcohol (neurolysis) or normal saline (control). The primary outcome was pain relief measured on a visual analogue scale. Opioid consumption, survival, quality of life, and adverse effects were also documented. Analgesics were managed using a protocol common to all centers. Patients were followed up for 8 months or until death.Results: Ninety-six patients (48 for each group) were included in the analysis. Pain relief with neurolysis was greater for the first 3 months (largest at the first month; mean difference, 0.7 [95% CI, 0.3 to 1.0]; adjusted P < 0.001) compared with placebo injection. Opioid consumption with neurolysis was lower for the first 5 months (largest at the first month; mean difference, 95.8 [95% CI, 67.4 to 124.1]; adjusted P < 0.001) compared with placebo injection. There was a significant difference in survival (hazard ratio, 1.56 [95% CI, 1.03 to 2.35]; P = 0.036) between groups. A significant reduction in survival in neurolysis was found for stage IV patients (hazard ratio, 1.94 [95% CI, 1.29 to 2.93]; P = 0.001), but not for stage III patients (hazard ratio, 1.08 [95% CI, 0.59 to 1.97]; P = 0.809). No differences in quality of life were observed.Conclusions: Neurolytic splanchnic nerve block appears to be an effective option for controlling pain and reducing opioid requirements in patients with unresectable pancreatic cancer.Editor’s Perspective: [ABSTRACT FROM AUTHOR]

Purpose: Women who develop gestational hypertension have evidence of elevated muscle sympathetic nerve activity (MSNA) in early pregnancy, which continues to rise after diagnosis. Exercise has been shown to play a preventative role in the development of gestational hypertension and has been shown to reduce resting and reflex MSNA in nonpregnant populations. We sought to investigate whether aerobic exercise affected the sympathetic regulation of blood pressure between the second and third trimesters of pregnancy. Methods: We conducted a randomized controlled trial of structured aerobic exercise (n = 31) compared with no intervention (control, n = 28) beginning at 16–20 wk and continuing until 34–36 wk of gestation (NCT02948439). Women in the exercise group were prescribed aerobic activity at 50%–70% of their heart rate reserve, on 3–4 d·wk−1 for 25–40 min with a 5-min warm-up and 5-min cool-down (i.e., up to 160 min total activity per week). At preintervention and postintervention assessments, data from ~10 min of quiet rest and a 3-min cold pressor test were analyzed to determine sympathetic nervous system activity and reactivity. Results: MSNA was obtained in 51% of assessments. Resting MSNA burst frequency and burst incidence increased across gestation (main effect of gestational age, P = 0.002). Neurovascular transduction was blunted in the control group (P = 0.024) but not in exercisers (P = 0.873) at the postintervention time point. Lastly, MSNA reactivity during the cold pressor test was not affected by gestational age or exercise (P = 0.790, interaction). Conclusions: These data show that exercise attenuates both the rise in MSNA and the blunting of neurovascular transduction. This may partially explain the lower risk of developing gestational hypertension in women who are active during their pregnancies. [ABSTRACT FROM AUTHOR]

Stretching (ST), an exercise modality widely used for flexibility improvement, has been recently proposed as an effective adjunct therapy for declines in cardiovascular health, warranting research into the effects of ST exercise on cardiac autonomic function (CAF). Heart rate (HR) variability (HRV) is a reliable measure of CAF, mainly the sympathetic and parasympathetic modulations of HR. A low HRV has been associated to increased risk of cardiovascular events and mortality. Exercise interventions that enhance HRV are therefore seen as beneficial to cardiovascular health and are sought after. In this review, we discuss the effect of ST both acute and training on HRV. Stretching training seems to be a useful therapeutic intervention to improve CAF in different populations. Although the mechanisms by which ST training improves CAF are not yet well understood; increases in baroreflex sensitivity, relaxation, and nitric oxide bioavailability seem to play an important role. [ABSTRACT FROM AUTHOR]

Objective: To examine differences in heart rate (HR) responses during international wheelchair rugby competition between athletes with and without a cervical spinal cord injury (SCI) and across standardized sport classifications. Design: Observational study. Setting: The 2015 Parapan American Games wheelchair rugby competition. Participants: Forty-three male athletes (31 ± 8 years) with a cervical SCI (n = 32) or tetraequivalent impairment (non-SCI, n = 11). Main Outcome Measures: Average and peak HR (HRavg and HRpeak, respectively). To characterize HR responses in accordance with an athletes' International Wheelchair Rugby Federation (IWRF) classification, we separated athletes into 3 groups: group I (IWRF classification 0.5-1.5, n = 15); group II (IWRF classification 2.0, n = 15); and group III (IWRF classification 2.5-3.5, n = 13). Results: Athletes with SCI had lower HRavg (111 ± 14 bpm vs 155 ± 13 bpm) and HRpeak (133 ± 12 bpm vs 178 ± 13 bpm) compared with non-SCI (both P < 0.001). Average HR was higher in group III than in I (136 M 25 bpm vs 115 M 20 bpm, P=0.045); however, SCI athletes showed no difference in HRavg or HRpeak between groups. Within group III, SCI athletes had lower HRavg (115 ± 6 bpm vs 160 ± 8 bpm) and HRpeak (135 ± 11 bpm vs 183 ± 11 bpm) than non-SCI athletes (both P < 0.001). Conclusions: This study is the first to demonstrate attenuated HR responses during competition in SCI compared with non-SCI athletes, likely due to injury to spinal autonomic pathways. Among athletes with SCI, IWRF classification was not related to differences in HR. Specific assessment of autonomic function after SCI may be able to predict HR during competition and consideration of autonomic impairments may improve the classification process. [ABSTRACT FROM AUTHOR]

Background: Clinical response to left ventricular assist devices (LVADs), as measured by health-related quality of life, varies among patients after implantation; however, it is unknown which pathophysiological mechanisms underlie differences in clinical response by health-related quality of life. Objective: The purpose of this study was to compare changes in sympathetic markers (b-adrenergic receptor kinase-1 [bARK1], norepinephrine [NE], and 3,4-dihydroxyphenylglycol [DHPG]) between health-related quality of life clinical responders and nonresponders from pre-- to post--LVAD implantation. Methods:We performed a secondary analysis on a subset of data from a cohort study of patients from pre-- to 1, 3, and 6 months after LVAD implantation. Clinical response was defined as an increase of 5 points or higher on the Kansas City Cardiomyopathy Questionnaire Clinical Summary score from pre-- to6months post--LVAD implantation.We measured plasma bARK1 level with an enzyme-linked immunosorbent assay and plasma NE and DHPG levels with high-performance liquid chromatography with electrochemical detection. Latent growth curvemodeling was used to compare the trajectories ofmarkers between groups. Results: The mean (SD) age of the sample (n = 39) was 52.9 (13.2) years, and most were male (74.4%) and received LVADs as bridge to transplantation (69.2%). Preimplantation plasma bARK1 levels were significantly higher in clinical responders (n = 19) than in nonresponders (n = 20) (P = .001), but change was similar after LVAD (P = .235). Preimplantation plasma DHPG levels were significantly lower in clinical responders than in nonresponders (P = .002), but the change was similar after LVAD (P = .881). There were no significant differences in plasma NE levels. Conclusions: Preimplantation bARK1 and DHPG levels are differentiating factors between health-related quality of life clinical responders and nonresponders to LVAD, potentially signaling differing levels of sympathetic stimulation underlying clinical response. [ABSTRACT FROM AUTHOR]

Supplemental digital content is available in the text. Introduction: The acute blood pressure (BP) decrease is greater after evening than morning exercise, suggesting that evening training (ET) may have a greater hypotensive effect. Objective: This study aimed to compare the hypotensive effect of aerobic training performed in the morning versus evening in treated hypertensives. Methods: Fifty treated hypertensive men were randomly allocated to three groups: morning training (MT), ET, and control (C). Training groups cycled for 45 min at moderate intensity (progressing from the heart rate of the anaerobic threshold to 10% below the heart rate of the respiratory compensation point), while C stretched for 30 min. Interventions were conducted 3 times per week for 10 wk. Clinic and ambulatory BP and hemodynamic and autonomic mechanisms were evaluated before and after the interventions. Clinic assessments were performed in the morning (7:00–9:00 am) and evening (6:00–8:00 pm). Between–within ANOVA was used (P ≤ 0.05). Results: Only ET decreased clinic systolic BP differently from C and MT (morning assessment −5 ± 6 mm Hg and evening assessment −8 ± 7 mm Hg, P < 0.05). Only ET reduced 24 h and asleep diastolic BP differently from C and MT (−3 ± 5 and −3 ± 4 mm Hg, respectively, P < 0.05). Systemic vascular resistance decreased from C only in ET (P = 0.03). Vasomotor sympathetic modulation decreased (P = 0.001) and baroreflex sensitivity (P < 0.02) increased from C in both training groups with greater changes in ET than MT. Conclusions: In treated hypertensive men, aerobic training performed in the evening decreased clinic and ambulatory BP due to reductions in systemic vascular resistance and vasomotor sympathetic modulation. Aerobic training conducted at both times of day increases baroreflex sensitivity, but with greater after ET. [ABSTRACT FROM AUTHOR]

Introduction/Purpose: We demonstrated that patients with obstructive sleep apnea (OSA) have reduced muscle metaboreflex control of muscle sympathetic nerve activity (MSNA). In addition, exercise training increased muscle metaboreflex control in heart failure patients. Objective: We tested the hypothesis that exercise training would increase muscle metaboreflex control of MSNA in patients with OSA. Methods: Forty-one patients with OSA were randomized into the following two groups: 1) nontrained (OSANT, n = 21) and 2) trained (OSAT, n = 20). Muscle sympathetic nerve activity was assessed by microneurography technique, muscle blood flow (FBF) by venous occlusion plethysmography, heart rate by electrocardiography, and blood pressure with an automated oscillometric device. All physiological variables were simultaneously assessed at rest, during isometric handgrip exercise at 30% of the maximal voluntary contraction, and during posthandgrip muscle ischemia (PHMI). Muscle metaboreflex sensitivity was calculated as the difference in MSNA between PHMI and the rest period. Patients in the OSAT group underwent 72 sessions of moderate exercise training, whereas patients in the OSANT group were clinical follow-up for 6 months. Results: The OSANT and OSAT groups were similar in anthropometric, neurovascular, hemodynamic and sleep parameters. Exercise training reduced the baseline MSNA (34 ± 2 bursts per minute vs 25 ± 2 bursts per minute; P < 0.05) and increased the baseline FBF (2.1 ± 0.2 mL·min−1 per 100 g vs 2.4 ± 0.2 mL·min−1 per 100 g; P < 0.05). Exercise training significantly reduced MSNA levels and increased FBF responses during isometric exercise. Exercise training significantly increased MSNA responses during PHMI (Δ6.5 ± 1 vs −1.7 ± 1 bursts per minute, P < 0.01). No significant changes in FBF or hemodynamic parameters in OSANT patients were found. Conclusions: Exercise training increases muscle metaboreflex sensitivity in patients with OSA. This autonomic change associated with increased muscle blood flow may contribute to the increase in exercise performance in this set of patients. [ABSTRACT FROM AUTHOR]

Purpose: Overload training is hypothesized to alter autonomic regulation, although interpretations using indirect measures of heart rate variability are conflicting. The aim of the present study was to examine the effects of overload training on muscle sympathetic nerve activity (MSNA), a direct measure of central sympathetic outflow, in recreational endurance athletes. Methods: Measurements of heart rate variability, cardiac baroreflex sensitivity (BRS), MSNA (microneurography), and sympathetic BRS were obtained in 17 healthy triathletes and cyclists after 1 wk of reduced training (baseline) and again after 3 wk of either regular (n = 7) or overload (n = 10) training. Results: After training, the changes (Δ) in peak power output (10 ± 10 vs -12 ± 9 W, P < 0.001), maximal heart rate (-2 ± 4 vs -8 ± 3 bpm, P = 0.006), heart rate variability (SD of normal-to-normal intervals, 27 ± 31 vs -3 ± 25 ms; P = 0.04), and cardiac BRS (7±6 vs -2 ± 8 ms-mm Hg-1, P = 0.02) differed between the control and overload groups. The change in MSNA burst frequency (-2 ± 2vs4 ± 5 bursts per minute, P = 0.02) differed between groups. Across all participants, the changes in resting MSNA and peak power output were correlated negatively (r = -0.51, P = 0.04). No between-group differences in resting heart rate or blood pressure were observed (all P > 0.05). Conclusions: Overload training increased MSNA and attenuated increases in cardiac BRS and heart rate variability observed with regular training. These results support neural adaptations after overload training and suggest that increased central sympathetic outflow may be linked with decreased exercise performance. [ABSTRACT FROM AUTHOR]

Purpose: Increased resting muscle sympathetic nerve activity (MSNA) and lower forearm blood flow (FBF) were observed in young men who use anabolic androgenic steroids (AAS). However, the response of MSNA and FBF in AAS users triggered by muscle mechanoreflex and central command has never been tested. In addition, we evaluated the blood pressure (BP) and heart rate (HR) responses during these maneuvers. Methods: Nineteen AAS users (AASU) 31 ± 6 yr of age and 18 AAS nonusers (AASNU) 29 ± 4 yr of age were recruited. All participants were involved in strength training. AAS use was determined using a urine test (liquid chromatography with tandem mass spectrometry). MSNA was measured using the microneurography technique. FBF was measured by using venous occlusion plethysmography. BP was measured using an automatic oscillometric device. HR was recorded continuously through ECG. Isometric handgrip exercise was performed at 30% of the maximal voluntary contraction for 3 min, and mental stress was elicited by the Stroop color-word test for 4 min. Results: The MSNA and FBF responses during exercise were similar between AASU and AASNU, with a trend toward higher MSNA (bursts per minute; P = 0.084) and lower forearm vascular conductance (FVC; units; P = 0.084) in AASU than in AASNU. During mental stress, AASU showed a significantly higher MSNA (P G 0.05) and lower FBF (P < 0.05) compared with AASNU. During both maneuvers, HR and BP increased linearly in both groups; however, AASU showed a significantly higher HR compared with AASNU. Conclusions: During muscle mechanoreflex activation (isometric exercise), AASU have normal MSNA and FBF responses, whereas during central command (mental stress) stimulation, AASU have exacerbated MSNA and blunted vasodilation. Therefore, mental stress seems to exacerbate neurovascular control throughout stress reaction situations in AASU. [ABSTRACT FROM AUTHOR]

Purpose: Ischemic preconditioning (IPC), a procedure that involves the cyclic induction of limb ischemia and reperfusion via tourniquet inflation, has been reported to improve exercise capacity and performance, but the underlying mechanisms remain unclear. During exercise, sympathetically mediated vasoconstriction is dampened in active skeletal muscle. This phenomenon, termed functional sympatholysis, plays a critical role in maintaining oxygen delivery to working skeletal muscle and may contribute to determining exercise capacity. Herein, we investigate the effects of IPC on functional sympatholysis in humans., Methods: In 20 (10M/10F) healthy young adults, forearm blood flow (Doppler ultrasound) and beat-to-beat arterial pressure (finger photoplethysmography) were measured during lower body negative pressure (LBNP; -20 mm Hg) applied at rest and simultaneously during rhythmic handgrip exercise (30% maximum contraction) before and after local IPC (4 × 5-min 220 mm Hg) or sham (4 × 5-min 20 mm Hg). Forearm vascular conductance (FVC) was calculated as forearm blood flow/mean arterial pressure and the magnitude of sympatholysis as the difference of LBNP-induced changes in FVC between handgrip and rest., Results: At baseline, LBNP decreased FVC (females [F] = ∆-41% ± 19%; males [M] = ∆-44% ± 10%), and these responses were attenuated during handgrip (F = ∆-8% ± 9%; M = ∆-8% ± 7%). After IPC, LBNP induced similar decreases in resting FVC (F = ∆-37% ± 19%; M = ∆-44% ± 13%). However, during handgrip, this response was further attenuated in males (∆-3% ± 9%, P = 0.02 vs pre) but not females (∆-5% ± 10%, P = 0.13 vs pre), which aligned with an IPC-mediated increase in sympatholysis (M-pre = 36% ± 10% vs post = 40% ± 9%, P = 0.01; F-pre = 32% ± 15% vs post = 32% ± 14%, P = 0.82). Sham IPC had no effect on any variables., Conclusions: These findings highlight a sex-specific effect of IPC on functional sympatholysis and provide evidence of a potential mechanism underlying the beneficial effects of IPC on human exercise performance., (Copyright © 2023 by the American College of Sports Medicine.)

Background: Current-generation left ventricular assist devices provide circulatory support that is minimally or entirely nonpulsatile and are associated with marked increases in muscle sympathetic nerve activity (MSNA), likely through a baroreceptor-mediated pathway. We sought to determine whether the restoration of pulsatile flow through modulations in pump speed would reduce MSNA through the arterial baroreceptor reflex.Methods and Results: Ten men and 3 women (54 ± 14 years) with Heartmate II continuous-flow left ventricular assist devices underwent hemodynamic and sympathetic neural assessment. Beat-to-beat blood pressure, carotid ultrasonography at the level of the arterial baroreceptors, and MSNA via microneurography were continuously recorded to determine steady-state responses to step changes (200-400 revolutions per minute) in continuous-flow left ventricular assist device pump speed from a maximum of 10,480 ± 315 revolutions per minute to a minimum of 8500 ± 380 revolutions per minute. Reductions in pump speed led to increases in pulse pressure (high versus low speed: 17 ± 7 versus 26 ± 12 mm Hg; P<0.01), distension of the carotid artery, and carotid arterial wall tension (P<0.05 for all measures). In addition, MSNA was reduced (high versus low speed: 41 ± 15 versus 33 ± 16 bursts per minute; P<0.01) despite a reduction in mean arterial pressure and was inversely related to pulse pressure (P=0.037).Conclusions: Among subjects with continuous-flow left ventricular assist devices, the restoration of pulsatile flow through modulations in pump speed leads to increased distortion of the arterial baroreceptors with a subsequent decline in MSNA. Additional study is needed to determine whether reduction of MSNA in this setting leads to improved outcomes. [ABSTRACT FROM AUTHOR]

PURPOSE: To examine the effects of repeated moderate heat exposure (RMHE) on muscle sympathetic nerve activity (MSNA) and cardiovascular control in healthy individuals. METHODS: We performed the RMHE with 4 weeks (5 days/week) warm baths (~40 deg C) for 30 min in 9 healthy older (59 ± 2 yrs) volunteers. Hemodynamic variables and MSNA were examined in a laboratory at ~23 deg C prior, 1 day after and 1 week after end of RMHE. A cold pressor test and handgrip exercise were performed during the testing sessions. RESULTS: Under normothermic conditions, the resting MSNA burst rate (prior, post, post 1-wk: 31.6 ± 2.0, 25.2 ± 2.0, 27.7 ± 1.7 bursts/min; P < 0.001) and burst incidence (P < 0.001) significantly decreased after RMHE. Moreover, the resting heart rate significantly decreased after RMHE (62.3 ± 1.6, 59.5 ± 2.0, 58.2 ± 1.6 beats/min, P < 0.05). The LF/HF ratio also decreased after RMHE. The sensitivity of baroreflex control of MSNA and heart rate were not altered by RMHE, although the baroreflex operating point was reset. The MSNA and hemodynamic responses (i.e. changes) to handgrip exercise or the cold pressor test were not altered. CONCLUSIONS: In this age group, RMHE evoked by warm baths decreases resting sympathetic activity and HR, which can be considered as beneficial effects. The mechanism(s) should be examined in future studies.Supported by National Institutes of Health Grants MPI R01 HL141198 (Li and Cui) and UL1 TR002014 (Sinoway). [ABSTRACT FROM AUTHOR]

Previous research suggests that ingesting a bitter tastant enhances exercise performance. This may be due to activation of the sympathetic nervous system (SNS) in response to the unpleasant taste. However, the mechanisms facilitating changes in performance after ingestion of unpleasant tastants are not yet clear. PURPOSE: To explore the effect of unpleasant tastants on SNS activity, corticomotor excitability, and neuromuscular function. METHODS: Five females and seven males participated in a three-phase experiment. Each phase had two presentations of five conditions in a random order. No solution, water and artificial sweetener were controls for the unpleasant salty (1 M) and bitter (2 mM quinine) solutions. Measurements were taken immediately after each 25 ml solution was mouth rinsed (10 s) and ingested. In Phase 1, hedonic value, nausea, heart rate, and mean arterial pressure were measured to determine perceptual and SNS responses. In Phase 2, quadricep motor evoked potentials (MEPs) were recorded following transcranial magnetic stimulation to assess corticomotor excitability. In Phase 3, quadricep maximal voluntary contractions were performed with electrical femoral nerve stimulation to assess neuromuscular function. One-way repeated measures ANOVAs, with Bonferroni post-hoc comparisons explored differences between conditions. RESULTS: Hedonic value rating was significantly higher (p < 0.05) in the salt (mean ± SD; 75 ± 8) and bitter (76 ± 8) conditions compared to water (47 ± 10) and artificial sweetener (28 ± 18). The increase in heart rate was significantly higher (p < 0.05) in the salt (23 ± 6 bpm) and bitter (21 ± 3 bpm) conditions compared to no solution (13 ± 4 bpm), water (17 ± 4 bpm), and artificial sweetener (18 ± 5 bpm). Change in mean arterial pressure was also significantly higher (p < 0.05) in the bitter (24 ± 5 mmHg) condition compared to no solution (18 ± 3 mmHg), but other conditions were not significantly different. There was no significant difference (p > 0.05) between conditions in nausea, neuromuscular function (max voluntary force, voluntary activation, rate of force development) or corticomotor excitability (MEPs). CONCLUSIONS: Unpleasant tastants influenced markers of SNS activation. However, this did not translate into changes in corticomotor excitability or neuromuscular function. [ABSTRACT FROM AUTHOR]

The article reports on research which was conducted to investigate the physiological impact that three varieties of stun guns or human electromuscular incapacitation devices (EMDs) had on anesthetized pigs. Researchers found that in healthy adult animals, despite the prolonged muscular exertion and physiological stress caused by EMD devices, the animals' bodies should be able to mount an appropriate sympathetic response and recover normally.

The article presents a study which examines the neural circulatory control in two vasovagal syncope (VVS) phenotypes such as low blood pressure (BP) VVS (LBPS) and normal BP VVS. The study performs sympathetic nervous testing among VVS patients during head-up tilt (HUT). Result shows microneurography in the normal level on subjects with normal BP during HUT, but is accentuated in low BP subjects. Moreover, norepinephrine spillover was subnormal in both patients during the HUT.

Background: Although the tendon of the long head of the biceps is a well-known source of shoulder pain, the pathophysiological basis of this pain has yet to be explained. The aim of this study was to detect and characterize any nervous element of the tendon and to determine a possible explanation for pain originating from this structure. Methods: The nature of the neuronal innervation of the tendon of the long head of the biceps was studied immunohistochemically, in four tendons from different human cadavers, with use of neurofilament antibody 2H3, neurofilament-like antibody 3A10, calcitonin gene-related peptide, substance P, and tyrosine hydroxylase. Results: A large neuronal network, asymmetrically distributed along the length of the tendon with a higher degree of innervation at the tendon origin, was identified by the neurofilament and neurofilament-like antibodies 2H3 and 3A10. This innervation was found to be positive for calcitonin gene-related peptide and substance P, suggesting the presence of thinly myelinated or unmyelinated sensory neurons. It was also positive for tyrosine hydroxylase, suggesting a post-ganglionic sympathetic origin. Conclusions and Clinical Relevance: These findings demonstrate that the tendon of the long head of the biceps is innervated by a network of sensory sympathetic fibers, which may play a role in the pathogenesis of shoulder pain. [ABSTRACT FROM AUTHOR]

PURPOSE: Orthostasis causes a gravity-dependent redistribution of blood volume to the lower extremities. The baroreflex coordinates an effector response through the sympathetic nervous system (SNS) to the peripheral vasculature to buffer changes in systolic blood pressure (SBP). In autonomic dysfunction (AD), impaired or exaggerated responses may lead to orthostatic hypotension (OHypo) or hypertension (OHTN). AD is becoming an increasingly recognized consequence of an acute concussion injury. The purpose of this study was to evaluate the SNS responses to orthostasis in recently concussed athletes. METHODS: A prospective study was performed in 32 concussed college athletes (gender: 22 female, 10 male; age: 20±1 yrs; height: 1.74±0.11 m; weight: 74±13 kg) and 14 athlete controls (gender: 8 female, 6 male; age: 20±2 yrs; height: 1.70±0.10 m; weight: 69±13 kg). Beat-to-beat SBP was assessed digitally at rest for 10 minutes in the supine (SUP) position and then for 3 minutes in the standing (STND) position within 48 hours (48H) of concussion. The change in SBP (ΔSBP) was computed from the difference between SUP and the final 15 seconds of STND. ΔSBP was then categorized as Normal (NR: ΔSBP -19 to +19 mmHg); OHypo (SBP fall ≥20 mmHg); and, OHTN (SBP rise ≥20 mmHg) for each group. Fast-Fourier transform was performed and power calculated for the total, very low, low and high frequency power (TP, vLF, LF and HF, respectively) spectra in each position; the variables were log10 transformed for parametric analyses. RESULTS: Fourteen control and 14 concussion participants had a NR ΔSBP, whereas 11 concussion participants had OHypo and 7 had OHTN. There were no differences across these four groups for the TP, vLF, LF, and HF in the SUP position. In the STND position, TP (p<0.0001), vLF (p<0.0001), and HF (p<0.05) were significant for the omnibus model. Bonferroni post hoc analyses revealed that the OHypo concussion group had a significantly lower TP and vLF than each of the 3 other groups, and the OHTN concussion group had a significant elevation and trend toward a significant elevation of HF compared to the OHypo and NR concussion groups, respectively. CONCLUSIONS: Different mechanisms appear to contribute to and influence AD during orthostasis within 48H of concussion injury. [ABSTRACT FROM AUTHOR]

Obesity is often associated with a high incidence of cardiovascular complications. Over the years there has been an increase in young adults that have been faced with this disease. Many factors can contribute to cardiovascular complications, but the adipose tissue regulation of the hormone leptin has become a focus of recent interest. Looking at this specifically, in combination with salivary biomarkers, attempts to explain a possible role of the sympathetic nervous system (SNS) in metabolic syndrome and hypertension. Further, changes in salivary composition, such as increased protein content, have been noted with increased sympathetic activation. PURPOSE: The aim of this study was to assess the differences in salivary biomarker levels of obese and overweight college age students. METHODS: Thirty-five (19 females and 16 males) college students gave written informed consent to participate in this study (age: 21.6 ± 1.0 yr., body fat 19.8 ± 8.9 percent). Participants were scheduled to report in the morning in a fasted state, having refrained from brushing their teeth, for a single 30- minute session in the Human Performance Laboratory. Body composition was tested via the BOD POD® (Life Measurements Inc, Concord, California, USA). Saliva was collected into 2.0 mL cryovials via passive drool. The samples were then frozen at -35°C until the completion of data collection. Analysis of the salivary leptin was performed via ELISA Assay and analysis of salivary protein and DNA was performed via Qubit 3.0 Fluorometer. RESULTS: Salivary leptin (146.31 ± 97.99 pg/ml) DNA (688.71 ± 1139.39 micrograms/ml) and Protein (0.40 ± 0.07 mg/ml) were detected in all samples. Salivary DNA and Leptin data were found to be non-normally distributed (A² > 5.2, p<0.001) and thus were log transformed before further analysis. Data analysis via Pearson's correlations revealed body fat was not significantly correlated to either Salivary Leptin (r=0.221, p=0.195) or Salivary DNA (r=0.257, p=0.136). Body Fat was significantly correlated to salivary protein (r=0.350, p=0.039). CONCLUSIONS:The data from the present study demonstrate increased morning SNS activity via salivary protein is present in overweight and obese college age students. Altered SNS activity may play a role in the etiology and/or complications of obesity. [ABSTRACT FROM AUTHOR]

PURPOSE: Individuals infected with the novel coronavirus SARS-CoV-2 exhibit a wide variety of symptoms, indicating potential systemic effects of the virus. However, the impact of COVID-19 on autonomic and cardiovascular function in otherwise healthy individuals remains largely unclear. METHODS: Otherwise healthy young adults (n=14, 8F; 20 ± 1 yr; 172 ± 11 cm; 72 ± 14 kg; 25 ± 3 kg·m-2) who had tested positive for SARS-CoV-2 (COV+) came to the laboratory approximately 3 weeks post-diagnosis. Muscle sympathetic nerve activity (MSNA; n=5) via microneurography, beat-by-beat systolic (SBP) and diastolic (DBP) arterial blood pressure, and heart rate (HR) were continuously measured at rest, during a 2 min cold pressor test (CPT), and during 5 min each at 30° and 60° head up tilt (HUT). RESULTS: Resting SBP (COV+: 124 ± 16 vs. CON: 128 ± 13 mmHg), DBP (75 ± 15 vs. 75 ± 8 mmHg), HR (64 ± 10 vs. 66 ± 9 bpm), and MSNA (18 ± 6 vs. 12 ± 5 bursts/min, p=0.13) were similar between COV+ subjects and other healthy subjects (CON; n=10, 8F; 21 ± 4 years; 169 ± 6 cm; 75 ± 12 kg; 26 ± 3 kg·m-2) undergoing the same protocol in our laboratory. Age, height, body mass, and BMI were not different between COV+ and CON groups. During the CPT, HR and SBP were higher in COV+ compared with CON (HR: 75 ± 4 vs. 71 ± 4, p=0.036; and SBP: 147 ± 3 vs. 132 ± 4 mmHg, p=0.014), and DBP tended to be higher (DBP: 93 ± 3 vs. 85 ± 4 mmHg, p=0.094, partial η2=0.14). However, preliminary data indicate the MSNA response to CPT is similar between COV+ subjects and healthy young adults (p=0.27). Blood pressure, HR, and MSNA responses to HUT were also similar between groups (p>0.05), though COV+ subjects tended to exhibit a larger, but still normal, increase in HR from supine to 60° HUT compared with CON (ΔHR: +24 ± 8 bpm vs. +18 ± 7 bpm, p=0.10). CONCLUSION: Resting autonomic and hemodynamic parameters appear normal in individuals who have previously contracted SARS-CoV-2. However, COV+ subjects may display exaggerated HR and SBP responses to painful stimuli, as well as a potentially greater HR response to orthostatic stress, compared with CON. Given the similar MSNA but differential blood pressure and HR responses between COV+ and healthy young adults during CPT and HUT, the transduction of MSNA into vascular responses may be exaggerated during physiological stress following infection with SARS-CoV-2. [ABSTRACT FROM AUTHOR]

In the past decade, efforts to improve blood pressure control have looked beyond conventional approaches of lifestyle modification and drug therapy to embrace interventional therapies. Based upon animal and human studies clearly demonstrating a key role for the sympathetic nervous system in the etiology of hypertension, the newer technologies that have emerged are predominantly aimed at neuromodulation of peripheral nervous system targets. These include renal denervation, baroreflex activation therapy, endovascular baroreflex amplification therapy, carotid body ablation, and pacemaker-mediated programmable hypertension control. Of these, renal denervation is the most mature, and with a recent series of proof-of-concept trials demonstrating the safety and efficacy of radiofrequency and more recently ultrasound-based renal denervation, this technology is poised to become available as a viable treatment option for hypertension in the foreseeable future. With regard to baroreflex activation therapy, endovascular baroreflex amplification, carotid body ablation, and programmable hypertension control, these are developing technologies for which more human data are required. Importantly, central nervous system control of the circulation remains a poorly understood yet vital component of the hypertension pathway and mandates further investigation. Technology to improve blood pressure control through deep brain stimulation of key cardiovascular control territories is, therefore, of interest. Furthermore, alternative nonsympathomodulatory intervention targeting the hemodynamics of the circulation may also be worth exploring for patients in whom sympathetic drive is less relevant to hypertension perpetuation. Herein, we review the aforementioned technologies with an emphasis on the preclinical data that underpin their rationale and the human evidence that supports their use.

The exercise pressor reflex (EPR) is engaged upon the activation of group III/IV skeletal muscle afferents and is one of the principal mediators of cardiovascular responses to exercise. This review explores the hypothesis that afferent signals from EPR communicate via GABAergic contacts within the brain stem to evoke parasympathetic withdrawal and sympathoexcitation to increase cardiac output, peripheral resistance, and blood pressure during exercise.

Introduction: Physical exercise triggers efferent cardiac sympathetic activation. Here, we tracked the spatiotemporal properties of cardiac repolarization on a beat-to-beat basis throughout a standardized exercise test and hypothesized a detectable change at the point of the anaerobic threshold (AT)., Methods: The study included 20 healthy adults (age 35.3 ± 6.7 yr) undergoing a standardized incremental exercise test on a cycle ergometer. During exercise testing, high-resolution (2000 Hz) ECG monitoring in Frank lead configuration was performed. Three-dimensional beat-to-beat repolarization instability (dT°) was assessed by a novel vector-based method according to a previously published technology. In parallel, the lactate threshold (LT) was detected according to Dickhuth and Mader., Results: We could identify a characteristic pattern of dT° signal during exercise testing. With increasing physical activity, dT° increased concordantly to heart rate. At an average of 164 ± 38 W, dT° and heart rate abruptly showed a discordant behavior, characterized by a transient drop of dT°. The maximal discordance between dT° and heart rate was defined as ATdT° and highly significantly correlated with LTDickhuth (r = 0.841, P < 0.001) and LTMader (r = 0.819, P < 0.001), which were at 156 ± 39 and 172 ± 46 W, respectively. The characteristic of dT° could not be provoked by fast atrial pacing in the absence of exercise., Conclusions: Repolarization instability shows a characteristic pattern during standardized exercise in healthy individuals that allows for a noninvasive estimation of AT.

Introduction: Detecting the onset of functional overreaching (FOR) or nonfunctional overreaching in endurance athletes is of prior importance to ensure reactive amendment of the scheduled training program. The objective of this study was to assess photoplethysmography (PPG) in overloaded athletes and test whether 1) it would be affected differently in functional overreached (FOR) or nonoverreached acutely fatigued (AF) athletes and 2) specific PPG characteristics would allow for timely distinction of FOR and AF., Methods: Fifteen athletes performed 2-wk baseline training followed by 3-wk overload (+45%; OVL) and 2-wk recovery (-20%). Three-thousand-meter time-trial running was used to assess performance at the end of baseline, OVL, and recovery and distinguish FOR and AF. PPG was recorded overnight using a wearable sensor, every third night. Overnight means and variances of systolic, diastolic, and dicrotic amplitudes and times as well as systolic and diastolic slopes were used to discriminate FOR and AF athletes., Results: Performance was decreased in FOR and improved in AF at the end of OVL. Diastolic time was greater in AF than FOR, whereas systolic slope was smaller in AF than in FOR during OVL. The variances of systolic, diastolic, dicrotic amplitudes, systolic, diastolic slopes, and pulse areas were smaller in AF compared with FOR in the last week of OVL., Conclusion: PPG is an efficient tool for the detection of overreaching because it distinguished FOR and AF athletes during OVL (prior performance decrement). This fast-responding method would therefore allow for adjusting the daily training content to prevent nonfunctional overreaching.

A correction is presented to the article “Three Weeks of Overload Training Increases Resting Muscle Sympathetic Activity" which appeared in a 2018 issue.

Objective- Sympathetic nerve innervation of vascular smooth muscle cells (VSMCs) is a major regulator of arteriolar vasoconstriction, vascular resistance, and blood pressure. Importantly, α-adrenergic receptor stimulation, which uniquely couples with Panx1 (pannexin 1) channel-mediated ATP release in resistance arteries, also requires localization to membrane caveolae. Here, we test whether localization of Panx1 to Cav1 (caveolin-1) promotes channel function (stimulus-dependent ATP release and adrenergic vasoconstriction) and is important for blood pressure homeostasis. Approach and Results- We use in vitro VSMC culture models, ex vivo resistance arteries, and a novel inducible VSMC-specific Cav1 knockout mouse to probe interactions between Panx1 and Cav1. We report that Panx1 and Cav1 colocalized on the VSMC plasma membrane of resistance arteries near sympathetic nerves in an adrenergic stimulus-dependent manner. Genetic deletion of Cav1 significantly blunts adrenergic-stimulated ATP release and vasoconstriction, with no direct influence on endothelium-dependent vasodilation or cardiac function. A significant reduction in mean arterial pressure (total=4 mm Hg; night=7 mm Hg) occurred in mice deficient for VSMC Cav1. These animals were resistant to further blood pressure lowering using a Panx1 peptide inhibitor Px1IL2P, which targets an intracellular loop region necessary for channel function. Conclusions- Translocalization of Panx1 to Cav1-enriched caveolae in VSMCs augments the release of purinergic stimuli necessary for proper adrenergic-mediated vasoconstriction and blood pressure homeostasis.

Objective: Changes in heart rate variability (HRV) associated with breathing (respiratory sinus arrhythmia) are known to be parasympathetically (vagally) mediated when the breathing rate is within the typical frequency range (9-24 breaths per minute [bpm]; high-frequency HRV). Slow yogic breathing occurs at rates below this range and increases low-frequency HRV power, which may additionally reflect a significant sympathetic component. Yogic breathing techniques are hypothesized to confer health benefits by increasing cardiac vagal control, but increases in low-frequency HRV power cannot unambiguously distinguish sympathetic from parasympathetic contributions. The aim of this study was to investigate the autonomic origins of changes in low-frequency HRV power due to slow-paced breathing., Methods: Six healthy young adults completed slow-paced breathing with a cadence derived from yogic breathing patterns. The paced breathing took place under conditions of sympathetic blockade, parasympathetic (vagal) blockade, and placebo. HRV spectral power was compared under 11 breathing rates during each session, in counterbalanced order with frequencies spanning the low-frequency range (4-9 bpm)., Results: HRV power across the low-frequency range (4-9 bpm) was nearly eliminated (p = .016) by parasympathetic blockade (mean (SD) spectral power at breathing frequency = 4.1 (2.1)) compared with placebo (69.5 (8.1)). In contrast, spectral power during sympathetic blockade 70.2 (9.1) and placebo (69.5 (8.1)) was statistically indistinguishable (p = .671)., Conclusions: These findings clarify the interpretation of changes in HRV that occur during slow-paced breathing by showing that changes in low-frequency power under these conditions are almost entirely vagally mediated. Slow-paced breathing is an effective tool for cardiac vagal activation.

Aspirin is known to interfere with platelet function and can protect individuals at risk of sudden death. However, this property of aspirin is less defined for cardiac autonomic activity. We assessed pulse rate variability by spectral analysis and measured plasma eicosanoid levels before and after administration of 81-mg aspirin to 12 healthy subjects over a 60-degree head-up tilt test in the morning. In upright posture, low-dose aspirin decreased both the normalized unit value of low-frequency (normalized LF) power (mean ± SD, 82.5 ± 4.5 vs. 77.5 ± 6.5 nu, P = 0.01) and LF/HF ratio (6.0 ± 2.1 vs. 4.7 ± 2.7, P = 0.02) and augmented the normalized unit value of high-frequency power (15.0 ± 4.4 vs. 19.8 ± 6.4 nu, P = 0.004). It simultaneously upregulated plasma 6-keto-PGF1α level (13.4 ± 6.8 vs. 19.7 ± 12.8 pg/mL, P = 0.04) and inhibited plasma thromboxane B2 (TXB2) level (11.6 ± 7.3 vs. 6.3 ± 4.2 pg/mL, P = 0.003). In the upright posture, both before and after aspirin, there was a significant direct correlation between plasma TXB2 levels and the normalized LF power (r = 0.42, P = 0.04) as well as between the plasma TXB2/6-keto-PGF1α ratio and the normalized LF power (r = 0.50, P = 0.01). Administration of low-dose aspirin in healthy people inhibits cardiac sympathetic activation and vagal withdrawal response to morning rising through an alternation of the TXA2/PGI2 balance.

Objective: Drug-eluting stent-induced coronary hyperconstricting responses remain an important issue. The adventitia harbors a variety of components that potently modulate vascular tone, including sympathetic nerve fibers (SNF) and vasa vasorum. Catheter-based renal denervation (RDN) inhibits sympathetic nerve activity. We, thus, examined whether RDN suppresses drug-eluting stent-induced coronary hyperconstricting responses, and if so, what mechanisms are involved., Approach and Results: Protocol 1: pigs implanted with everolimus-eluting stents into the left coronary arteries underwent coronary angiography at 1 month after implantation for assessment of coronary vasomotion and adventitial SNF formation. Drug-eluting stent-induced coronary hyperconstricting responses were significantly enhanced associated with enhanced coronary adventitial SNF and vasa vasorum formation. Protocol 2: pigs implanted with everolimus-eluting stents were randomly assigned to the RDN or sham group. The RDN group underwent renal ablation. At 1 month, RDN significantly caused marked damage of the SNF at the renal arteries without any stenosis, thrombus, or dissections. Notably, RDN significantly upregulated the expression of α 2 -adrenergic receptor-binding sites in the nucleus tractus solitarius, attenuated muscle sympathetic nerve activity, and decreased systolic blood pressure and plasma renin activity. In addition, RDN attenuated coronary hyperconstricting responses to intracoronary serotonin at the proximal and distal stent edges associated with decreases in SNF and vasa vasorum formation, inflammatory cell infiltration, and Rho-kinase expression/activation. Furthermore, there were significant positive correlations between SNF and vasa vasorum and between SNF and coronary vasoconstricting responses., Conclusions: These results provide the first evidence that RDN ameliorates drug-eluting stent-induced coronary hyperconstricting responses in pigs in vivo through the kidney-brain-heart axis., (© 2017 American Heart Association, Inc.)

Purpose: To study the contribution of each eye to the reflex tear response, after unilateral and bilateral topical anesthesia., Method: A closed-eye, modified Schirmer test was performed bilaterally in 8 normal subjects, in a controlled environment chamber set to 23°C, 45% relative humidity, and 0.08 m/s airflow. Eye drops were instilled into each eye 10 minutes before the Schirmer test. Experiments were as follows: 1) bilateral saline (control), 2) unilateral anesthesia (ipsilateral anesthetic; contralateral saline), and 3) bilateral anesthesia., Results: There was no difference in between-eye wetting lengths in the saline control eyes (P = 0.394) or the bilaterally anesthetized eyes (P = 0.171). The wetting length was reduced in both eyes after bilateral anesthesia compared with saline controls (P = 0.001; P ≤ 0.0005). After unilateral anesthesia, the wetting length was reduced in the anesthetized eye compared with its saline control by 51.4% (P ≤ 0.0005) and compared with its fellow, unanesthetized eye (P = 0.005). The fellow eye value was also reduced compared with its saline control (P = 0.06)., Conclusions: The wetting length was reduced by topical anesthesia, when instilled bilaterally and ipsilaterally. The latter response implies an ipsilateral, reflex sensory drive to lacrimal secretion. In the unanesthetized fellow eye, the reduction compared with its saline control was not quite significant. This implies a relative lack of central, sensory, reflex cross-innervation, although the possibility cannot entirely be ruled out. These results are relevant to the possibility of reflex lacrimal compensation from a normal fellow eye, in cases of unilateral corneal anesthesia.

Objective: Stellate ganglion block has mostly been used to relieve symptoms of neuropathic pain; several potential complications have been reported. Noninvasive stellate ganglion block application using light irradiation (SG-LI) can be used as an alternative to conventional injection blockades. Based on the variety of application protocols among previous studies, it was needed to further identify the clinical efficacy of SG-LI in managing neuropathic pain or other disorders associated with sympathetic hyperactivity., Design: A comprehensive search of online databases was performed to identify experimental or observational studies reporting the efficacy of SG-LI in treating patients with disorders requiring sympatholytic management. The included studies were subjected to a meta-analysis and risk-of-bias assessment., Results: Twenty-one experimental studies with a Physiotherapy Evidence Database score of 6/10 and 5 observational studies with a Newcastle-Ottawa scale score of 7/9 were included in the analysis. A significant effect on pain relief favoring SG-LI was identified at a standard mean difference (SMD) of -2.05 [95% confidence interval (CI), -2.49 to -1.61; P < 0.00001]. Similar effects favoring SG-LI were found in peripheral blood flow (SMD, 1.26; 95% CI, 0.26-2.25; P = 0.01) and skin temperature (SMD, 1.31; 95% CI, 0.55, 2.08; P = 0.0007)., Conclusions: Stellate ganglion block application using light irradiation effectively relieves pain of various etiologies and successfully induces a sympatholytic response. Stellate ganglion block application using light irradiation may be a valuable addition to the contemporary pain management armamentarium.

The beat-to-beat blood pressure (BP) monitoring parameters, such as average beat-to-beat BP, BP variability (BPV), could have an influence on the vascular elasticity. This study hypothesized that the elevated beat-to-beat BPV could evoke the reduction of the vascular elasticity independent of BP levels. We measured the beat-to-beat BP recordings and total arterial compliance (TAC), which was used to assess the vascular elasticity, in 80 young healthy adults during the cold pressor test (CPT). The CPT included 3 phases: baseline phase, cold stimulus phase, recovery phase. Six parameters were used to estimate BPV. In bivariate correlation analysis, TAC showed a significant correlation with systolic BP (SBP) and diastolic BP (DBP) in the cold stimulus phase; and 4 indices of SBP variability (SBPV) were associated with TAC (r = 0.271∼0.331, P ≤ 0.015) in the recovery phase; similarly, 2 indices of DBP variability (DBPV) were also correlated with TAC (r = 0.221∼0.285, P ≤ 0.048) in the recovery phase. In multivariate regression analysis, DBPV (β = 0.229, P = 0.001) was a determinant of TAC independent of average DBP, sex, and weight. In addition, both beat-to-beat BP and BPV values increased in the cold stimulus phase (P < 0.01); whereas, the TAC decreased in the cold stimulus phase (P < 0.01). In conclusion, these data suggest that the beat-to-beat DBPV shows an independent association with the vascular elasticity in young normal adults during the CPT.

Background: Global iodine-123 metaiodobenzylguanidine (I-MIBG) uptake is predictive of cardiovascular events and mortality in patients with heart failure. Normal variations in global and regional uptake, however, are not well defined and few studies have addressed the functional relevance of I-MIBG uptake and distribution in healthy individuals., Materials and Methods: We performed I-MIBG scintigraphy and cardiac autonomic function testing using the standardized methodology in 15 healthy individuals (mean age 54.6±5.3 years, male : female 10 : 5) with no evidence of previous myocardial infarction or ischaemic heart disease., Results: Early heart to mediastinum ratio (HMR) was 1.67±0.13, late HMR was 1.73±0.16 and washout rate was 19.09±7.63% (4.20-31.30). Regional analysis showed reduced tracer uptake at the apex, base and inferior wall in all individuals. Early and late HMR correlated negatively with RFa (r=-0.603; P=0.05 and r=-0.644; P=0.033) and expiration and inspiration ratio (r=-0.616; P=0.043 and r=-0.676; P=0.022) and positively with LFa/RFa (r=0.711; P=0.014 and r=0.784; P=0.004). Washout rate correlated only with RFa (r=0.642; P=0.033)., Conclusion: Healthy adults show a heterogeneous pattern of cardiac innervation with reduced regional uptake of I-MIBG. Furthermore, HMR correlates with indices of cardiac sympathetic function, suggesting that it might not only be a useful prognostic marker but may also provide insight into the functional integrity of the cardiac autonomic nervous system.

Sympathetic hyperactivation during tracheal intubation prolongs the QT interval and increases the risk of arrhythmias. We investigated if dexmedetomidine pretreatment affected autonomic nervous system balance and QT intervals during intubation. Sixty-six patients were randomized to receive 1.0 μg/kg fentanyl (group F, n = 22), 0.5 μg/kg dexmedetomidine (group D0.5, n = 22), or 1.0 μg/kg dexmedetomidine (group D1.0, n = 22) before induction. Autonomic nervous system balance was assessed by the ratio of low-frequency/high-frequency (LF/HF) power for heart rate variability at baseline (T0), before intubation (T1), and after intubation (T2). QT intervals were corrected by the Bazett's formula (QTc) and compared at baseline, before intubation, and 1, 2, and 3 minutes after intubation. The LF/HF ratio was higher after intubation compared with that at T0 in group F (P < 0.001). There were no significant changes in groups D0.5 and D1.0. The LF/HF ratio was significantly higher in group F compared with those in groups D0.5 and D1.0 after intubation (7.9 vs. 2.1 and 2.5; P < 0.001). The heart rate was increased for 3 minutes after intubation in group F, whereas only for 1 minute after intubation in groups D0.5 and D1.0, compared with that at baseline. More patients in group F had QTc greater than 440 ms compared with that in group D0.5 or D1.0 (8 vs. 1 and 2; P = 0.005) at 1 minute after intubation. In contrast to 1.0 μg/kg fentanyl, pretreatment with 0.5 or 1.0 μg/kg dexmedetomidine suppressed sympathetic hyperactivity and attenuated QTc prolongation during intubation.

Objectives: Dynamic autonomic activity changes have been repeatedly reported during electroconvulsive therapy (ECT). However, the specific timing of these changes remains unclear. To clarify whether sympathetic or parasympathetic nervous activity contributes separately to the second stage and the third stage during and after induced seizures by ECT, we examined heart rate (HR) and spectral analysis of variability (HRV) during ECT., Methods: Seventeen patients with depression participated in the study and underwent ECT. The R-R intervals (RRI) were recorded and analyzed sequentially for the HRV indices high-frequency (HF) (an index of parasympathetic activity) and low-frequency (LF)/high-frequency (an index of sympathetic activity) for 4 minutes before and after stimulus onset by the maximum entropy method. Averaged HRs were compared between 3 heart beats prestimulus and poststimulus onset. The HRV power in the range of 30 to 80 and 80 to 130 seconds after a seizure was compared between the HF and LF/HF components., Results: There was a significant reduction of the averaged HR over 3 HRs just after stimulus onset, suggesting parasympathetic dominance in the first phase. The LF/HF power significantly increased in the 30 to 80 s range after stimulus onset, whereas the HF power significantly increased in the 80 to 130 s range after stimulus onset, reflecting sympathetic activation in the second phase and parasympathetic activation in the third phase, respectively., Conclusions: The evaluation of HR and HRV revealed a triphasic change from parasympathetic to sympathetic to parasympathetic cardiac autonomic activity after ECT stimulus onset in depression patients.

Background: Renal denervation (RDN) emerged as a therapeutic option for resistant hypertension. Nerve regrowth after RDN has been questioned. We aimed to characterize the nerve response after RDN., Methods and Results: Swine underwent bilateral RDN and were followed up for 7, 30, and 90 days and evaluated with S100 (Schwann cell), tyrosine hydroxylase (TH; efferent nerves), and growth-associated protein 43 (neurite regeneration) markers. At 7 days, nerve changes consisted of necrosis associated with perineurial fibrosis and distal atrophy with inflammation. At 30 days changes were substituted by healing changes (ie, fibrosis). This response progressed through 90 days resulting in prominent neuroma formation. Immunohistochemistry at 7 days: TH staining was strongly decreased in treated nerves. Early regenerative attempts were observed with strongly TH and growth-associated protein 43 positive and weak S100 disorganized nerve sprouts within the thickened perineurium. Distal atrophic nerves show weak staining for all 3 markers. At 30 days, affected nerves show a weak TH and S100 staining. Evident growth-associated protein 43+ disorganized neuromatous tangles in the thickened perineurium of severed nerves were observed. At 90 days, some TH expression was observed together with prominent S100+ and growth-associated protein 43+ neuromatous tangles with disorganized architecture. The potential for regenerative activity is unlikely based on the disrupted architecture of these neuromatous tangles at the radiofrequency lesion sites., Conclusions: This study is the first documentation that a progressive regenerative response occurs as early as 7 days after RDN, resulting in a poorly organized neuromatous regeneration. This finding is of paramount importance to further establish the potential functional significance of a regeneration after RDN., (© 2015 American Heart Association, Inc.)

Regulation of vascular tone is a complex response that integrates multiple signals that allow for blood flow and oxygen supply to match oxygen demand appropriately. Here, we discuss the potential role of intravascular adenosine triphosphate (ATP) as a primary factor in these responses and put forth the hypothesis that deficient ATP release contributes to impairments in vascular control exhibited in aged and diseased populations.