Pub Date : 2025-04-19DOI: 10.1016/j.autneu.2025.103281
Jaiden Uppal, Jacquie R. Baker, Rashmin Hira, Kavithra Karalasingham, Shaun Ranada, Paras Deol, Robert S. Sheldon, Satish R. Raj
Head-up tilt (HUT) and active stand tests (AST) are used in the diagnosis of Postural Orthostatic Tachycardia Syndrome (POTS), but their relative diagnostic accuracy is unclear. This necessitates a direct comparison under standardized conditions. We aimed to compare the hemodynamic responses and diagnostic accuracy of AST vs. HUT in POTS.
To address this, patients with POTS (n = 60) completed a 10-min AST followed by HUT on the same day. Beat-to-beat hemodynamics were recorded during 10-min supine baselines and each test. Delta values were calculated for each test (upright 1-min averages minus baseline average).
Δ[heart rate] increased significantly over time (1_Min: 28 bpm to 10_Min: 40 bpm; PTime < 0.001), and was greater for HUT (33 bpm vs. 37 bpm; PASTvHUT = 0.01), with significant Time x Condition interaction (38 bpm vs. 42 bpm at10min; PINT < 0.001). Δ[stroke volume] declined over time (1_Min: -18 ml to 10_Min: -32 ml); PTime < 0.001), with no significant test or interaction effects (PASTvHUT = 0.36; PINT = 0.21). Δ[SBP] decreased (1_Min: −0.3 mmHg to 10_Min: −5.7 mmHg); PTime < 0.001) over time, with no test or interaction effects.
Fewer patients met POTS heart rate criteria during the AST (AST: 74 % vs. HUT: 98 %; p < 0.001). Lowering the threshold to 27 bpm for AST narrowed the gap but was still significantly higher for HUT (AST: 83 % vs HUT: 98 %; p = 0.02).
Orthostatic tachycardia differs between AST and HUT in patients with POTS. The proportion of patients with POTS meeting the heart rate diagnostic criteria differs significantly between AST and HUT, a discrepancy that can be mitigated by lowering the heart rate threshold for the AST.
{"title":"Physiological and clinical comparison of active stand and head-up tilt tests in Postural Orthostatic Tachycardia Syndrome (POTS)","authors":"Jaiden Uppal, Jacquie R. Baker, Rashmin Hira, Kavithra Karalasingham, Shaun Ranada, Paras Deol, Robert S. Sheldon, Satish R. Raj","doi":"10.1016/j.autneu.2025.103281","DOIUrl":"10.1016/j.autneu.2025.103281","url":null,"abstract":"<div><div>Head-up tilt (HUT) and active stand tests (AST) are used in the diagnosis of Postural Orthostatic Tachycardia Syndrome (POTS), but their relative diagnostic accuracy is unclear. This necessitates a direct comparison under standardized conditions. We aimed to compare the hemodynamic responses and diagnostic accuracy of AST vs. HUT in POTS.</div><div>To address this, patients with POTS (<em>n</em> = 60) completed a 10-min AST followed by HUT on the same day. Beat-to-beat hemodynamics were recorded during 10-min supine baselines and each test. Delta values were calculated for each test (upright 1-min averages minus baseline average).</div><div>Δ[heart rate] increased significantly over time (1_Min: 28 bpm to 10_Min: 40 bpm; P<sub>Time</sub> < 0.001), and was greater for HUT (33 bpm vs. 37 bpm; P<sub>ASTvHUT</sub> = 0.01), with significant Time x Condition interaction (38 bpm vs. 42 bpm at10min; P<sub>INT</sub> < 0.001). Δ[stroke volume] declined over time (1_Min: -18 ml to 10_Min: -32 ml); P<sub>Time</sub> < 0.001), with no significant test or interaction effects (P<sub>ASTvHUT</sub> = 0.36; P<sub>INT</sub> = 0.21). Δ[SBP] decreased (1_Min: −0.3 mmHg to 10_Min: −5.7 mmHg); P<sub>Time</sub> < 0.001) over time, with no test or interaction effects.</div><div>Fewer patients met POTS heart rate criteria during the AST (AST: 74 % vs. HUT: 98 %; <em>p</em> < 0.001). Lowering the threshold to 27 bpm for AST narrowed the gap but was still significantly higher for HUT (AST: 83 % vs HUT: 98 %; <em>p</em> = 0.02).</div><div>Orthostatic tachycardia differs between AST and HUT in patients with POTS. The proportion of patients with POTS meeting the heart rate diagnostic criteria differs significantly between AST and HUT, a discrepancy that can be mitigated by lowering the heart rate threshold for the AST.</div></div>","PeriodicalId":55410,"journal":{"name":"Autonomic Neuroscience-Basic & Clinical","volume":"260 ","pages":"Article 103281"},"PeriodicalIF":3.2,"publicationDate":"2025-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143860591","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-04-13DOI: 10.1016/j.autneu.2025.103279
Feng Hu , Yali Wang , Minhua Zang , Guangyu Li , Guangyu Wang , Danfeng Hu , Lihui Zheng , Yan Yao , Jun Pu
Background
Myocardial infarction (MI) often leads to complications like ventricular arrhythmias and heart failure, driven by autonomic nervous system imbalance. This study evaluates the effectiveness of a novel remote-controlled vagal nerve stimulation (VNS) device, featuring adjustable stimulation parameters post-implantation, specifically focusing on its potential to inhibit ventricular arrhythmias and prevent the progression of heart failure in a rat model of acute MI.
Methods
Male Sprague-Dawley rats were randomized, and MI was induced by ligation of the left anterior descending artery. Seven days post-MI, rats were divided into three groups: the MI + VNS group (n = 15), the MI + control group (n = 15), and a sham-operated group (n = 12). In the MI + VNS group, a VNS device was implanted with initial stimulation settings of 0.2 mA, 0.2 ms pulse width, and 20 Hz frequency. During follow-up, stimulation parameters were adjusted to maintain a 5–20 % reduction in heart rate from baseline. Cardiac function, arrhythmia inducibility, and myocardial fibrosis were assessed four weeks after VNS implantation.
Results
Remote-controlled VNS significantly improved left ventricular ejection fraction and fractional shortening compared to the MI + control group (all P < 0.001). The left ventricular end-systolic diameter was also significantly reduced (P = 0.003). Additionally, VNS-treated rats exhibited a lower incidence and duration of ventricular arrhythmias (P = 0.003) and a reduction in myocardial fibrosis (P < 0.001). Plasma levels of B-type natriuretic peptide and noradrenaline were also significantly lower in the VNS group compared to controls (all P < 0.001).
Conclusions
These findings suggest that remote-controlled VNS offers a novel and dynamic approach to treating MI-related complications. By allowing for adaptive stimulation in response to real-time physiological changes, remote-controlled VNS may represent a valuable strategy for reducing the risk of heart failure and arrhythmias post-MI.
{"title":"Remote-controlled vagal nerve stimulation attenuates ventricular arrhythmias and prevents heart failure progression in a rat model of acute myocardial infarction","authors":"Feng Hu , Yali Wang , Minhua Zang , Guangyu Li , Guangyu Wang , Danfeng Hu , Lihui Zheng , Yan Yao , Jun Pu","doi":"10.1016/j.autneu.2025.103279","DOIUrl":"10.1016/j.autneu.2025.103279","url":null,"abstract":"<div><h3>Background</h3><div>Myocardial infarction (MI) often leads to complications like ventricular arrhythmias and heart failure, driven by autonomic nervous system imbalance. This study evaluates the effectiveness of a novel remote-controlled vagal nerve stimulation (VNS) device, featuring adjustable stimulation parameters post-implantation, specifically focusing on its potential to inhibit ventricular arrhythmias and prevent the progression of heart failure in a rat model of acute MI.</div></div><div><h3>Methods</h3><div>Male Sprague-Dawley rats were randomized, and MI was induced by ligation of the left anterior descending artery. Seven days post-MI, rats were divided into three groups: the MI + VNS group (<em>n</em> = 15), the MI + control group (n = 15), and a sham-operated group (<em>n</em> = 12). In the MI + VNS group, a VNS device was implanted with initial stimulation settings of 0.2 mA, 0.2 ms pulse width, and 20 Hz frequency. During follow-up, stimulation parameters were adjusted to maintain a 5–20 % reduction in heart rate from baseline. Cardiac function, arrhythmia inducibility, and myocardial fibrosis were assessed four weeks after VNS implantation.</div></div><div><h3>Results</h3><div>Remote-controlled VNS significantly improved left ventricular ejection fraction and fractional shortening compared to the MI + control group (all <em>P</em> < 0.001). The left ventricular end-systolic diameter was also significantly reduced (<em>P</em> = 0.003). Additionally, VNS-treated rats exhibited a lower incidence and duration of ventricular arrhythmias (<em>P</em> = 0.003) and a reduction in myocardial fibrosis (<em>P</em> < 0.001). Plasma levels of B-type natriuretic peptide and noradrenaline were also significantly lower in the VNS group compared to controls (all <em>P</em> < 0.001).</div></div><div><h3>Conclusions</h3><div>These findings suggest that remote-controlled VNS offers a novel and dynamic approach to treating MI-related complications. By allowing for adaptive stimulation in response to real-time physiological changes, remote-controlled VNS may represent a valuable strategy for reducing the risk of heart failure and arrhythmias post-MI.</div></div>","PeriodicalId":55410,"journal":{"name":"Autonomic Neuroscience-Basic & Clinical","volume":"260 ","pages":"Article 103279"},"PeriodicalIF":3.2,"publicationDate":"2025-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143845088","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-04-12DOI: 10.1016/j.autneu.2025.103280
Gabriel do Carmo Silva , Maycon Junior Ferreira , Amanda Aparecida Araujo , Antonio Viana do Nascimento Filho , Nathalia Bernardes , Jônatas Bussador do Amaral , Maria Cláudia Irigoyen , Kátia De Angelis
<div><div>Antihypertensive drug and exercise training are commonly prescribed to treat arterial hypertension. However, there is a considerable gap in understanding how physiological mechanisms of male and female adapt to the combination of these approaches. Therefore, we focused to investigate sexual differences in cardiovascular, autonomic, inflammation and systemic oxidative stress adaptations in male and OVX female ovariectomized spontaneously hypertensive rats (SHR) treated with enalapril associated with moderate-intensity concurrent exercise training. Enalapril (3 mg/kg, diluted in drinking water) and exercise training (3 days/week, moderate intensity) was carried out for 8 weeks. Blood pressure (BP), heart rate (HR) and its variabilities were assessed. Serum and plasma were used for inflammatory and oxidative stress analyses. Enalapril, associated or not with exercise training, induced a reduction in diastolic and mean BP in both sexes; however, only the OVX female groups showed a reduction in systolic BP, as well as resting bradycardia. Both sexes showed improvements in BP and HR variability following the treatments; however, improvement in SD2/SD1 ratio, which indicates how much the heartbeats occur at irregular intervals, and in variance of systolic BP were observed only in trained groups. A higher spontaneous baroreflex sensitivity, as well as reduced IL-6/IL-10 were found only in the trained groups. Increased IL-10 was observed in male trained group (vs. other groups). Finally, combination enalapril and exercise training reduced systemic pro-oxidants such as NADPH oxidase and hydrogen peroxide. The findings of our study showed that OVX female SHR, after ovarian hormone deprivation, presented more pronounced effects on hemodynamics, BP variability, and anti-inflammatory profile than hypertensive males with the combination of treatments.</div></div><div><h3>Background</h3><div>Researchers are investigating how the body responds differently in males and females. These differences are also evident when examining how pharmacological and non-pharmacological approaches help the body control arterial hypertension. This study aimed to investigate how drug medication combined with exercise affects the heart's ability to self-regulate and how it relates to immune and oxidant defense, with a focus on differences in male and ovariectomized (OVX) female adaptations.</div></div><div><h3>Methods</h3><div>The study was conducted using hypertensive male and OVX female rats, allocated into: a) sedentary, b) enalapril, or c) enalapril plus exercise groups, totaling six groups (3 males and 3 OVX females, respectively). Enalapril (3 mg/kg/day) and exercise (aerobic and resistance exercises) were prescribed for eight weeks. The effects on blood pressure control, serum, and plasma were assessed.</div></div><div><h3>Results</h3><div>Although both males and OVX females showed improvements in blood pressure after medication, combined or not with exercise, OVX fe
{"title":"Cardiovascular and neuroimmune adaptations to enalapril and exercise training: A comparative study in male and ovariectomized female spontaneously hypertensive rats","authors":"Gabriel do Carmo Silva , Maycon Junior Ferreira , Amanda Aparecida Araujo , Antonio Viana do Nascimento Filho , Nathalia Bernardes , Jônatas Bussador do Amaral , Maria Cláudia Irigoyen , Kátia De Angelis","doi":"10.1016/j.autneu.2025.103280","DOIUrl":"10.1016/j.autneu.2025.103280","url":null,"abstract":"<div><div>Antihypertensive drug and exercise training are commonly prescribed to treat arterial hypertension. However, there is a considerable gap in understanding how physiological mechanisms of male and female adapt to the combination of these approaches. Therefore, we focused to investigate sexual differences in cardiovascular, autonomic, inflammation and systemic oxidative stress adaptations in male and OVX female ovariectomized spontaneously hypertensive rats (SHR) treated with enalapril associated with moderate-intensity concurrent exercise training. Enalapril (3 mg/kg, diluted in drinking water) and exercise training (3 days/week, moderate intensity) was carried out for 8 weeks. Blood pressure (BP), heart rate (HR) and its variabilities were assessed. Serum and plasma were used for inflammatory and oxidative stress analyses. Enalapril, associated or not with exercise training, induced a reduction in diastolic and mean BP in both sexes; however, only the OVX female groups showed a reduction in systolic BP, as well as resting bradycardia. Both sexes showed improvements in BP and HR variability following the treatments; however, improvement in SD2/SD1 ratio, which indicates how much the heartbeats occur at irregular intervals, and in variance of systolic BP were observed only in trained groups. A higher spontaneous baroreflex sensitivity, as well as reduced IL-6/IL-10 were found only in the trained groups. Increased IL-10 was observed in male trained group (vs. other groups). Finally, combination enalapril and exercise training reduced systemic pro-oxidants such as NADPH oxidase and hydrogen peroxide. The findings of our study showed that OVX female SHR, after ovarian hormone deprivation, presented more pronounced effects on hemodynamics, BP variability, and anti-inflammatory profile than hypertensive males with the combination of treatments.</div></div><div><h3>Background</h3><div>Researchers are investigating how the body responds differently in males and females. These differences are also evident when examining how pharmacological and non-pharmacological approaches help the body control arterial hypertension. This study aimed to investigate how drug medication combined with exercise affects the heart's ability to self-regulate and how it relates to immune and oxidant defense, with a focus on differences in male and ovariectomized (OVX) female adaptations.</div></div><div><h3>Methods</h3><div>The study was conducted using hypertensive male and OVX female rats, allocated into: a) sedentary, b) enalapril, or c) enalapril plus exercise groups, totaling six groups (3 males and 3 OVX females, respectively). Enalapril (3 mg/kg/day) and exercise (aerobic and resistance exercises) were prescribed for eight weeks. The effects on blood pressure control, serum, and plasma were assessed.</div></div><div><h3>Results</h3><div>Although both males and OVX females showed improvements in blood pressure after medication, combined or not with exercise, OVX fe","PeriodicalId":55410,"journal":{"name":"Autonomic Neuroscience-Basic & Clinical","volume":"260 ","pages":"Article 103280"},"PeriodicalIF":3.2,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143848677","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-04-05DOI: 10.1016/j.autneu.2025.103277
Alec L.E. Butenas , Ashley M. Baranczuk , Raimi J. Carroll , Shannon K. Parr , Carl J. Ade , K. Sue Hageman , Timothy I. Musch , Steven W. Copp
We investigated the role played by ATP-sensitive purinergic 2 × 4 (P2X4) receptors on the sensory endings of thin fibre muscle afferents in exercise pressor reflex and mechanoreflex activation in healthy/SHAM rats and rats with heart failure with reduced ejection fraction (HF-rEF). We hypothesized that infusion of the P2X4 receptor antagonist 5-BDBD (8 μg) into the hindlimb arterial supply would reduce the mean arterial pressure (MAP) and renal sympathetic nerve activity (RSNA) responses to 30s of electrically-induced hindlimb skeletal muscle contraction (model of exercise pressor reflex activation) and 30s of hindlimb skeletal muscle stretch (model of mechanoreflex activation) in decerebrate, unanesthetized HF-rEF rats but not SHAM rats. Ejection fraction was significantly lower in HF-rEF (46 ± 3 %) compared to SHAM (83 ± 2 %; P < 0.001) rats. In SHAM rats, P2X4 receptor blockade had no effect on the pressor response to hindlimb muscle contraction (n = 8) or the pressor and RSNA response to muscle stretch (n = 4). However, in SHAM rats we found that P2X4 receptor blockade significantly reduced the RSNA response to muscle contraction. In HF-rEF rats, P2X4 receptor blockade reduced the pressor and RSNA response to hindlimb muscle contraction (n = 7) as well as the pressor, but not the RNSA, response to hindlimb muscle stretch (n = 8). Collectively, the data suggest that P2X4 receptors on thin fibre muscle afferent sensory endings play a role in the evoking the exercise pressor reflex in healthy subjects that is limited to RSNA, and that in HF-rEF this expands to a significant role in mechanoreflex and exercise pressor reflex-mediated blood pressure control.
{"title":"Novel role for purinergic 2× subtype 4 (P2X4) receptors in the exercise pressor reflex and mechanoreflex: Effect of heart failure","authors":"Alec L.E. Butenas , Ashley M. Baranczuk , Raimi J. Carroll , Shannon K. Parr , Carl J. Ade , K. Sue Hageman , Timothy I. Musch , Steven W. Copp","doi":"10.1016/j.autneu.2025.103277","DOIUrl":"10.1016/j.autneu.2025.103277","url":null,"abstract":"<div><div>We investigated the role played by ATP-sensitive purinergic 2 × 4 (P2X4) receptors on the sensory endings of thin fibre muscle afferents in exercise pressor reflex and mechanoreflex activation in healthy/SHAM rats and rats with heart failure with reduced ejection fraction (HF-rEF). We hypothesized that infusion of the P2X4 receptor antagonist 5-BDBD (8 μg) into the hindlimb arterial supply would reduce the mean arterial pressure (MAP) and renal sympathetic nerve activity (RSNA) responses to 30s of electrically-induced hindlimb skeletal muscle contraction (model of exercise pressor reflex activation) and 30s of hindlimb skeletal muscle stretch (model of mechanoreflex activation) in decerebrate, unanesthetized HF-rEF rats but not SHAM rats. Ejection fraction was significantly lower in HF-rEF (46 ± 3 %) compared to SHAM (83 ± 2 %; <em>P</em> < 0.001) rats. In SHAM rats, P2X4 receptor blockade had no effect on the pressor response to hindlimb muscle contraction (<em>n</em> = 8) or the pressor and RSNA response to muscle stretch (<em>n</em> = 4). However, in SHAM rats we found that P2X4 receptor blockade significantly reduced the RSNA response to muscle contraction. In HF-rEF rats, P2X4 receptor blockade reduced the pressor and RSNA response to hindlimb muscle contraction (<em>n</em> = 7) as well as the pressor, but not the RNSA, response to hindlimb muscle stretch (<em>n</em> = 8). Collectively, the data suggest that P2X4 receptors on thin fibre muscle afferent sensory endings play a role in the evoking the exercise pressor reflex in healthy subjects that is limited to RSNA, and that in HF-rEF this expands to a significant role in mechanoreflex and exercise pressor reflex-mediated blood pressure control.</div></div>","PeriodicalId":55410,"journal":{"name":"Autonomic Neuroscience-Basic & Clinical","volume":"260 ","pages":"Article 103277"},"PeriodicalIF":3.2,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143825556","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-04-05DOI: 10.1016/j.autneu.2025.103278
Sophie É. Collins , Devin B. Phillips , Michael K. Stickland
Rationale
Chronic heart failure (CHF) and chronic obstructive pulmonary disease (COPD) are characterized by exaggerated carotid chemoreceptor (CC) sensitivity and exercise intolerance. We tested the hypothesis that participants with elevated CC sensitivity would have the greatest improvement in exercise tolerance with CC inhibition, secondary to increased vascular conductance, and lower ventilatory requirements, dyspnea and leg discomfort.
Methods
Data from healthy controls, and patients with CHF or COPD were included in this secondary analysis of results from 2 randomized placebo-controlled double-blind crossover trials. Assessments included pulmonary function, incremental cardiopulmonary exercise test, and basal CC sensitivity assessment. High CC sensitivity was defined as either a stepwise hypoxic ventilatory response (HVR) or transient HVR greater than one SD above the mean in healthy controls. Participants received 2 μg/kg/min dopamine or placebo infusions (randomized) during 2 separate constant work-rate exercise tests to examine exercise endurance time (EET) and cardiopulmonary responses.
Results
Among 33 adults, 17 were categorized to normal HVR (11 controls/3 COPD/3 CHF), and 16 to high HVR (1 control/7 COPD/8 CHF). Participants with high HVR experienced significant dopamine-induced improvements in EET (pinteraction = 0.011), and reduced leg discomfort at the 4-min isotime (pinteraction = 0.024). Those with improved vascular conductance and leg discomfort had the greatest improvements in EET (p = 0.042 and p = 0.021, respectively).
Conclusions
CC inhibition with dopamine in participants with high HVR was associated with improvement in EET. These findings suggest that high HVR is related to exercise limitation, and that improvement in EET is associated with a CC-mediated increase in vascular conductance and leg discomfort.
{"title":"Carotid chemoreceptor inhibition improves exercise tolerance in participants with elevated carotid chemosensitivity: A secondary analysis","authors":"Sophie É. Collins , Devin B. Phillips , Michael K. Stickland","doi":"10.1016/j.autneu.2025.103278","DOIUrl":"10.1016/j.autneu.2025.103278","url":null,"abstract":"<div><h3>Rationale</h3><div>Chronic heart failure (CHF) and chronic obstructive pulmonary disease (COPD) are characterized by exaggerated carotid chemoreceptor (CC) sensitivity and exercise intolerance. We tested the hypothesis that participants with elevated CC sensitivity would have the greatest improvement in exercise tolerance with CC inhibition, secondary to increased vascular conductance, and lower ventilatory requirements, dyspnea and leg discomfort.</div></div><div><h3>Methods</h3><div>Data from healthy controls, and patients with CHF or COPD were included in this secondary analysis of results from 2 randomized placebo-controlled double-blind crossover trials. Assessments included pulmonary function, incremental cardiopulmonary exercise test, and basal CC sensitivity assessment. High CC sensitivity was defined as either a stepwise hypoxic ventilatory response (HVR) or transient HVR greater than one SD above the mean in healthy controls. Participants received 2 μg/kg/min dopamine or placebo infusions (randomized) during 2 separate constant work-rate exercise tests to examine exercise endurance time (EET) and cardiopulmonary responses.</div></div><div><h3>Results</h3><div>Among 33 adults, 17 were categorized to normal HVR (11 controls/3 COPD/3 CHF), and 16 to high HVR (1 control/7 COPD/8 CHF). Participants with high HVR experienced significant dopamine-induced improvements in EET (p<sub>interaction</sub> = 0.011), and reduced leg discomfort at the 4-min isotime (p<sub>interaction</sub> = 0.024). Those with improved vascular conductance and leg discomfort had the greatest improvements in EET (<em>p</em> = 0.042 and <em>p</em> = 0.021, respectively).</div></div><div><h3>Conclusions</h3><div>CC inhibition with dopamine in participants with high HVR was associated with improvement in EET. These findings suggest that high HVR is related to exercise limitation, and that improvement in EET is associated with a CC-mediated increase in vascular conductance and leg discomfort.</div></div>","PeriodicalId":55410,"journal":{"name":"Autonomic Neuroscience-Basic & Clinical","volume":"260 ","pages":"Article 103278"},"PeriodicalIF":3.2,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143820525","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-04-04DOI: 10.1016/j.autneu.2025.103276
Keisho Katayama , Shigehiko Ogoh
Precise cardiovascular adjustments are necessary to meet the metabolic demands of working skeletal muscle during dynamic exercise. Appropriate regulation of sympathetic vasomotor outflow is key for maintaining arterial blood pressure (ABP) and facilitating the delivery of blood flow to active skeletal muscle. Central command, the exercise pressor reflex (including mechanoreflex and metaboreflex within skeletal muscle), and the arterial baroreflex work in concert, creating complex interactions that regulate sympathetic vasomotor outflow during dynamic exercise. Although less well studied, limited evidence suggests that the cardiopulmonary baroreflex plays a significant role in modulating MSNA (muscle sympathetic nerve activity) and ABP responses during mild-intensity dynamic exercise, as well as in resetting the arterial baroreflex during dynamic exercise. This review provides an updated and comprehensive overview of the sympathetic vasomotor outflow and the ABP response during dynamic exercise via the cardiopulmonary baroreflex.
{"title":"The role of cardiopulmonary baroreflex on sympathetic vasomotor outflow and blood pressure regulation during dynamic exercise","authors":"Keisho Katayama , Shigehiko Ogoh","doi":"10.1016/j.autneu.2025.103276","DOIUrl":"10.1016/j.autneu.2025.103276","url":null,"abstract":"<div><div>Precise cardiovascular adjustments are necessary to meet the metabolic demands of working skeletal muscle during dynamic exercise. Appropriate regulation of sympathetic vasomotor outflow is key for maintaining arterial blood pressure (ABP) and facilitating the delivery of blood flow to active skeletal muscle. Central command, the exercise pressor reflex (including mechanoreflex and metaboreflex within skeletal muscle), and the arterial baroreflex work in concert, creating complex interactions that regulate sympathetic vasomotor outflow during dynamic exercise. Although less well studied, limited evidence suggests that the cardiopulmonary baroreflex plays a significant role in modulating MSNA (muscle sympathetic nerve activity) and ABP responses during mild-intensity dynamic exercise, as well as in resetting the arterial baroreflex during dynamic exercise. This review provides an updated and comprehensive overview of the sympathetic vasomotor outflow and the ABP response during dynamic exercise via the cardiopulmonary baroreflex.</div></div>","PeriodicalId":55410,"journal":{"name":"Autonomic Neuroscience-Basic & Clinical","volume":"260 ","pages":"Article 103276"},"PeriodicalIF":3.2,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143839492","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-30DOI: 10.1016/j.autneu.2025.103275
Jeremy A. Bigalke, Jason R. Carter
Sleep and autonomic regulation are closely related processes which incur significant influence on health and wellbeing in women across the lifespan. Aging in women is associated with increases in cardiovascular risk through greater sympathetic predominance compared to premenopausal women, as well as reductions in sleep quality and quantity. Women remain an understudied population with regards to sleep, autonomic function, and cardiovascular risk. Understanding the interplay between sleep and autonomic function across the lifespan of women is crucial to improve subsequent lifelong health outcomes. The present review integrates knowledge that has accrued regarding experimental sleep deprivation, restriction, and chronic sleep disturbance and their respective impacts on autonomic regulation at various life stages in women. The review focuses on high-fidelity measures of sympathetic regulation (i.e., microneurography), as aging in women is associated with a disproportionate increase in sympathetic activity compared to men. Evidence summarized within this review delineates a significant impact of sleep processes on autonomic function in women across the lifespan. However, there remain substantial gaps in our knowledge of this interplay between sleep processes and autonomic regulation of cardiovascular control in women. There is a need for further research efforts to disentangle the complexity associated with sleep and autonomic regulation in women at all life stages. Efforts in this area will improve our understanding of women's health and factors such as sleep and sleep disturbance which precipitate lifelong health and chronic cardiovascular risk.
{"title":"The influence of sleep on autonomic nervous system regulation in women across the lifespan","authors":"Jeremy A. Bigalke, Jason R. Carter","doi":"10.1016/j.autneu.2025.103275","DOIUrl":"10.1016/j.autneu.2025.103275","url":null,"abstract":"<div><div>Sleep and autonomic regulation are closely related processes which incur significant influence on health and wellbeing in women across the lifespan. Aging in women is associated with increases in cardiovascular risk through greater sympathetic predominance compared to premenopausal women, as well as reductions in sleep quality and quantity. Women remain an understudied population with regards to sleep, autonomic function, and cardiovascular risk. Understanding the interplay between sleep and autonomic function across the lifespan of women is crucial to improve subsequent lifelong health outcomes. The present review integrates knowledge that has accrued regarding experimental sleep deprivation, restriction, and chronic sleep disturbance and their respective impacts on autonomic regulation at various life stages in women. The review focuses on high-fidelity measures of sympathetic regulation (i.e., microneurography), as aging in women is associated with a disproportionate increase in sympathetic activity compared to men. Evidence summarized within this review delineates a significant impact of sleep processes on autonomic function in women across the lifespan. However, there remain substantial gaps in our knowledge of this interplay between sleep processes and autonomic regulation of cardiovascular control in women. There is a need for further research efforts to disentangle the complexity associated with sleep and autonomic regulation in women at all life stages. Efforts in this area will improve our understanding of women's health and factors such as sleep and sleep disturbance which precipitate lifelong health and chronic cardiovascular risk.</div></div>","PeriodicalId":55410,"journal":{"name":"Autonomic Neuroscience-Basic & Clinical","volume":"260 ","pages":"Article 103275"},"PeriodicalIF":3.2,"publicationDate":"2025-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143776448","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-29DOI: 10.1016/j.autneu.2025.103274
John D. Akins, Takuro Washio, Qi Fu
Hypertension remains a leading cause of cardiovascular morbidity and mortality worldwide, with implications in women's health across the lifespan. Of note, autonomic nervous system imbalances have been linked to the development of hypertension and are present with natural aging and various conditions unique to women (e.g., menopause, hypertensive disorders of pregnancy, polycystic ovary syndrome). As such, this article reviews the critical changes in the sympathetic and parasympathetic nervous systems that occur in women and may contribute to the development of hypertension. Special focus is paid to the regulating pathways across the baroreflex arc, including baroreflex sensitivity, efferent sympathetic outflow, and peripheral sympathetic transduction, at rest and during various physiological stressors. To this point, aging women experience increasing sympathetic outflow, blunted sympathetic transduction, and reduced cardiovagal baroreflex sensitivity, which may be further potentiated by the presence of hypertension. Additionally, this review applies some clinical perspective to the physiological findings in order to identify potential therapeutic pathways. The information gathered in this review has important implications for future research into women's autonomic blood pressure regulation and its impact on the genesis of hypertension.
{"title":"Autonomic control of blood pressure in women: The roles of hypertension and aging","authors":"John D. Akins, Takuro Washio, Qi Fu","doi":"10.1016/j.autneu.2025.103274","DOIUrl":"10.1016/j.autneu.2025.103274","url":null,"abstract":"<div><div>Hypertension remains a leading cause of cardiovascular morbidity and mortality worldwide, with implications in women's health across the lifespan. Of note, autonomic nervous system imbalances have been linked to the development of hypertension and are present with natural aging and various conditions unique to women (e.g., menopause, hypertensive disorders of pregnancy, polycystic ovary syndrome). As such, this article reviews the critical changes in the sympathetic and parasympathetic nervous systems that occur in women and may contribute to the development of hypertension. Special focus is paid to the regulating pathways across the baroreflex arc, including baroreflex sensitivity, efferent sympathetic outflow, and peripheral sympathetic transduction, at rest and during various physiological stressors. To this point, aging women experience increasing sympathetic outflow, blunted sympathetic transduction, and reduced cardiovagal baroreflex sensitivity, which may be further potentiated by the presence of hypertension. Additionally, this review applies some clinical perspective to the physiological findings in order to identify potential therapeutic pathways. The information gathered in this review has important implications for future research into women's autonomic blood pressure regulation and its impact on the genesis of hypertension.</div></div>","PeriodicalId":55410,"journal":{"name":"Autonomic Neuroscience-Basic & Clinical","volume":"260 ","pages":"Article 103274"},"PeriodicalIF":3.2,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143783679","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-26DOI: 10.1016/j.autneu.2025.103272
Lauren E. Maier , Sarah E. Meyer , Andy Deprato , Stephen Busch , Allison Sivak , Margie H. Davenport , Craig D. Steinback
This systematic review and meta-analysis was conducted to quantify the sympathetic response to rhythmic handgrip exercise in healthy and diseased populations. Structured searches of databases were performed until June 12, 2024. We included all primary studies (other than systematic reviews and meta-analyses), and inclusion criteria were: population (all populations); intervention (rhythmic handgrip); comparator (baseline); and outcome (MSNA, BP, HR). Forty-nine studies (n = 930) were included. Burst frequency was elevated by 6.1 bursts/min during rhythmic handgrip (95 % CI, 4.52, 7.63; I2 = 53 %; p < 0.00001) across all populations. Similarly, burst incidence and total activity showed significant increases during handgrip (BI: MD, 3.0 bursts/100 hbs; 95 % CI, 0.11, 5.85; I2 = 0 %; p = 0.04; TA: MD, 49.4 a.u.; 95 % CI, 36.56, 62.20; I2 = 86 %; p < 0.00001). Subgroup analyses found greater responses in MSNA during rhythmic handgrip in healthy individuals compared to cardiovascular diseases and other conditions. Specifically, the change in burst frequency during handgrip (p = 0.0009) and total activity during handgrip (p < 0.00001) suggest a blunted sympathetic response to rhythmic handgrip in diseased populations. Meta-regression analyses in healthy populations found no relationship between the volume of handgrip applied with the associated change in sympathetic activity; however, there was a significant positive relationship between both the change in heart rate (slope = 0.131; adjusted R2 = 0.2773; p = 0.002) and the change in mean blood pressure (slope = 0.163; adjusted R2 = 0.3594; p < 0.001) with handgrip volume. An increase in MSNA is observed during rhythmic handgrip despite ranging protocols, populations, and co-interventions. These results suggest exercise is a unique stressor and challenges the understanding of general sympathetic hyperactivity in diseased populations.
{"title":"The effects of rhythmic handgrip exercise on muscle sympathetic nerve activity: A systematic review and meta-analysis","authors":"Lauren E. Maier , Sarah E. Meyer , Andy Deprato , Stephen Busch , Allison Sivak , Margie H. Davenport , Craig D. Steinback","doi":"10.1016/j.autneu.2025.103272","DOIUrl":"10.1016/j.autneu.2025.103272","url":null,"abstract":"<div><div>This systematic review and meta-analysis was conducted to quantify the sympathetic response to rhythmic handgrip exercise in healthy and diseased populations. Structured searches of databases were performed until June 12, 2024. We included all primary studies (other than systematic reviews and meta-analyses), and inclusion criteria were: population (all populations); intervention (rhythmic handgrip); comparator (baseline); and outcome (MSNA, BP, HR). Forty-nine studies (n = 930) were included. Burst frequency was elevated by 6.1 bursts/min during rhythmic handgrip (95 % CI, 4.52, 7.63; I<sup>2</sup> = 53 %; p < 0.00001) across all populations. Similarly, burst incidence and total activity showed significant increases during handgrip (BI: MD, 3.0 bursts/100 hbs; 95 % CI, 0.11, 5.85; I<sup>2</sup> = 0 %; p = 0.04; TA: MD, 49.4 a.u.; 95 % CI, 36.56, 62.20; I<sup>2</sup> = 86 %; p < 0.00001). Subgroup analyses found greater responses in MSNA during rhythmic handgrip in healthy individuals compared to cardiovascular diseases and other conditions. Specifically, the change in burst frequency during handgrip (p = 0.0009) and total activity during handgrip (p < 0.00001) suggest a blunted sympathetic response to rhythmic handgrip in diseased populations. Meta-regression analyses in healthy populations found no relationship between the volume of handgrip applied with the associated change in sympathetic activity; however, there was a significant positive relationship between both the change in heart rate (slope = 0.131; adjusted R<sup>2</sup> = 0.2773; p = 0.002) and the change in mean blood pressure (slope = 0.163; adjusted R<sup>2</sup> = 0.3594; p < 0.001) with handgrip volume. An increase in MSNA is observed during rhythmic handgrip despite ranging protocols, populations, and co-interventions. These results suggest exercise is a unique stressor and challenges the understanding of general sympathetic hyperactivity in diseased populations.</div></div>","PeriodicalId":55410,"journal":{"name":"Autonomic Neuroscience-Basic & Clinical","volume":"259 ","pages":"Article 103272"},"PeriodicalIF":3.2,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143791926","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-25DOI: 10.1016/j.autneu.2025.103271
E.L. Williams , J. Lando , V.-E.M. Lucci , B.C.D. Hockin , K. Elabd , S.N. Robinovitch , I.T. Parsons , V.E. Claydon
Counterpressure maneuvers (CPM) are movements used to delay or abort syncope, but may have practical barriers to use. We recently showed exaggerated postural sway produces protective responses against syncope. Accordingly, we aimed to evaluate a series of discreet, accessible movements as novel preventative CPM.
We tested 26 healthy adults (12 female) aged 28.9 ± 1.2 years. Participants performed a baseline stand (BL), followed by three randomized CPM trials (exaggerated anteroposterior sway, AP; toe clenching, TC; gluteal muscle clenching, GC). Non-invasive beat-to-beat systolic arterial pressure (SAP), heart rate, stroke volume (SV), cardiac output (CO), total peripheral resistance (TPR), mean middle cerebral artery blood velocity (mMCAv), and total path length moved (TPL) were measured. Muscularity was assessed using bioelectrical impedance.
All discreet CPM augmented orthostatic SV (p < 0.001) and CO (p < 0.001), while reducing TPR (p < 0.001). SAP increased during AP (p < 0.001) and GC (p < 0.001), but not TC. GC responses were unstable, with increased standard deviation of SAP (p = 0.002) and SV (p = 0.022) that may predispose syncope. Only AP improved mMCAv (p = 0.005) and sympathovagal balance (p < 0.001). Responses were largest in those with greater initial cardiovascular instability (p < 0.003), larger leg muscle mass (p < 0.02), and where TPL was greater (p < 0.002).
These novel CPM hold clinical potential for the prevention of orthostatic syncope and presyncope, while addressing real-world patient-reported barriers to CPM. Exaggerated AP sway was most robust and stable at improving orthostatic hemodynamics in healthy controls, with reduced reliance on sympathetic baroreflex-mediated vasoconstriction during enhanced muscle pumping activity. Accordingly, AP shows the most promise as a simple and discrete CPM.
{"title":"Orthostatic cardiovascular responses to postural sway and discreet counterpressure maneuvers","authors":"E.L. Williams , J. Lando , V.-E.M. Lucci , B.C.D. Hockin , K. Elabd , S.N. Robinovitch , I.T. Parsons , V.E. Claydon","doi":"10.1016/j.autneu.2025.103271","DOIUrl":"10.1016/j.autneu.2025.103271","url":null,"abstract":"<div><div>Counterpressure maneuvers (CPM) are movements used to delay or abort syncope, but may have practical barriers to use. We recently showed exaggerated postural sway produces protective responses against syncope. Accordingly, we aimed to evaluate a series of discreet, accessible movements as novel preventative CPM.</div><div>We tested 26 healthy adults (12 female) aged 28.9 ± 1.2 years. Participants performed a baseline stand (BL), followed by three randomized CPM trials (exaggerated anteroposterior sway, AP; toe clenching, TC; gluteal muscle clenching, GC). Non-invasive beat-to-beat systolic arterial pressure (SAP), heart rate, stroke volume (SV), cardiac output (CO), total peripheral resistance (TPR), mean middle cerebral artery blood velocity (mMCAv), and total path length moved (TPL) were measured. Muscularity was assessed using bioelectrical impedance.</div><div>All discreet CPM augmented orthostatic SV (<em>p</em> < 0.001) and CO (<em>p</em> < 0.001), while reducing TPR (<em>p</em> < 0.001). SAP increased during AP (<em>p</em> < 0.001) and GC (<em>p</em> < 0.001), but not TC. GC responses were unstable, with increased standard deviation of SAP (<em>p</em> = 0.002) and SV (<em>p</em> = 0.022) that may predispose syncope. Only AP improved mMCAv (<em>p</em> = 0.005) and sympathovagal balance (<em>p</em> < 0.001). Responses were largest in those with greater initial cardiovascular instability (<em>p</em> < 0.003), larger leg muscle mass (<em>p</em> < 0.02), and where TPL was greater (<em>p</em> < 0.002).</div><div>These novel CPM hold clinical potential for the prevention of orthostatic syncope and presyncope, while addressing real-world patient-reported barriers to CPM. Exaggerated AP sway was most robust and stable at improving orthostatic hemodynamics in healthy controls, with reduced reliance on sympathetic baroreflex-mediated vasoconstriction during enhanced muscle pumping activity. Accordingly, AP shows the most promise as a simple and discrete CPM.</div></div>","PeriodicalId":55410,"journal":{"name":"Autonomic Neuroscience-Basic & Clinical","volume":"260 ","pages":"Article 103271"},"PeriodicalIF":3.2,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143777539","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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