Saade MB, Holden S, Kakinami L
… +6 more, McGrath JJ, Mathieu MÈ, Poirier P, Barnett TA, Beaucage P, Henderson M
Clin Auton Res
· 2024 Dec · PMID 39304555
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PURPOSE: Data on associations between adiposity and heart rate variability (HRV) in prepubertal children are limited. We examined the associations between adiposity indices and HRV, independent of lifestyle behaviors, co...PURPOSE: Data on associations between adiposity and heart rate variability (HRV) in prepubertal children are limited. We examined the associations between adiposity indices and HRV, independent of lifestyle behaviors, comparing multiple indicators of adiposity, and explored differences between boys and girls. METHODS: Data stem from 469 participants of the QUALITY cohort (630 children aged 8-10 years with a parental history of obesity). Adiposity indices included waist-to-height ratio, body mass index (BMI) percentiles and categories (overweight, obesity), dual-energy x-ray absorptiometry (DEXA) defined fat mass percentage and android/gynoid ratio. HRV indices in the frequency and the spectral domain were derived from a daytime 3-h Holter recording. Multivariable linear regression models were adjusted for age, sex, Tanner stage, physical activity, screen time, and fitness. Interactions between sex and adiposity were tested. RESULTS: Greater adiposity was associated with decreased parasympathetic modulation and increased sympathetic dominance. Waist-to-height ratio was associated with lower parasympathetic activity: root mean square of the successive differences (RMSSD) [B = -23.32, 95% confidence interval (CI) -42.42, -4.22], pNN50 (B = -16.93, 95% CI - 28.58, - 5.27), LF/HF ratio (B = 1.83, 95% CI 0.97-2.70). Patterns of association were similar for android/gynoid ratio. Overweight was not associated with altered HRV. Obesity was negatively associated with RMSSD and pNN50 and positively with LF/HF ratio. Greater fat mass percentage was associated with lower RMSSD, pNN50, and HF, and increased LF/HF ratio. There were no differences between boys and girls. CONCLUSIONS: Specific markers of adiposity relate to altered HRV in childhood, with waist-to-height ratio being potentially a more relevant marker of HRV than BMI and more pragmatic than percent body fat. TRIAL REGISTRATION: NCT03356262, 11 November 2017.
Clin Auton Res
· 2024 Dec · PMID 39300002
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PURPOSE: A blood pressure stabilization during late phase II of Valsalva's maneuver may be utilized to confirm sympathetic vasoconstrictor control after a spinal cord injury. This study investigated whether Valsalva resp...PURPOSE: A blood pressure stabilization during late phase II of Valsalva's maneuver may be utilized to confirm sympathetic vasoconstrictor control after a spinal cord injury. This study investigated whether Valsalva response was predictive of hemodynamics during tilt or isometric handgrip. METHODS: Presence/absence of Valsalva response was compared to heart rate, mean arterial pressure, leg blood flow, and vascular resistance during head-up tilt and isometric handgrip to fatigue in 14 adults with spinal cord injury from C7 to T12 and 14 controls. Statistics were performed with two-way repeated measure analysis of variance (ANOVA), post hoc t-tests for between-group comparisons, and Mann-Whitney U tests for within-group. RESULTS: In total, six participants with spinal cord injury lacked a blood pressure stabilization for Valsalva's maneuver. However, this was not related to vasoconstrictor responses during the other tests. The groups had similar heart rate and blood pressure changes during tilt, though leg blood flow decreases and vascular resistance increases tended to be smaller at 20° tilt in those with spinal cord injury (p = 0.07 and p = 0.11, respectively). Participants with spinal cord injury had lower heart rates and markedly smaller blood pressure increases during handgrip (both p < 0.05). There were no group differences in leg blood flow, but those with spinal cord injury demonstrated a blunted vascular resistance increase by the final 10% of the handgrip (p < 0.01). CONCLUSIONS: Valsalva response was not consistent with hemodynamics during other stimuli, but some individuals evidence increases in sub-lesional vascular resistance to isometric handgrip comparable to controls, suggesting a sympathoexcitatory stimulus may be critical to provoke hemodynamic responses after spinal cord injury.
Mwesigwa N, Millar Vernetti P, Kirabo A
… +7 more, Black B, Ding T, Martinez J, Palma JA, Biaggioni I, Kaufmann H, Shibao CA
Clin Auton Res
· 2024 Dec · PMID 39294522
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PURPOSE: We previously reported that single doses of the norepinephrine transporter inhibitor, atomoxetine, increased standing blood pressure (BP) and ameliorated symptoms in patients with neurogenic orthostatic hypotens...PURPOSE: We previously reported that single doses of the norepinephrine transporter inhibitor, atomoxetine, increased standing blood pressure (BP) and ameliorated symptoms in patients with neurogenic orthostatic hypotension (nOH). We aimed to evaluate the effect of atomoxetine over four weeks in patients with nOH. METHODS: A randomized, double-blind, placebo-controlled crossover clinical trial between July 2016 and May 2021 was carried out with an initial open-label, single-dose phase (10 or 18 mg atomoxetine), followed by a 1-week wash-out, and a subsequent double-blind 4-week treatment sequence (period 1: atomoxetine followed by placebo) or vice versa (period 2). The trial included a 2-week wash-out period. The primary endpoint was symptoms of nOH as measured by the orthostatic hypotension questionnaire (OHQ) assessed at 2 weeks. RESULTS: A total of 68 patients were screened, 40 were randomized, and 37 completed the study. We found no differences in the OHQ composite score between atomoxetine and placebo at 2 weeks (-0.3 ± 1.7 versus -0.4 ± 1.5; P = 0.806) and 4 weeks (-0.6 ± 2.4 versus -0.5 ± 1.6; P = 0.251). There were no differences either in the OHSA scores at 2 weeks (3 ± 1.9 versus 4 ± 2.1; P = 0.062) and at 4 weeks (3 ± 2.2 versus 3 ± 2.0; P = 1.000) or in the OH daily activity scores (OHDAS) at 2 weeks (4 ± 3.0 versus 5 ± 3.1, P = 0.102) and 4 weeks (4 ± 3.0 versus 4 ± 2.7, P = 0.095). Atomoxetine was well-tolerated. CONCLUSIONS: While previous evidence suggested that acute doses of atomoxetine might be efficacious in treating nOH; results of this clinical trial indicated that it was not superior to placebo to ameliorate symptoms of nOH. TRIAL REGISTRATION: ClinicalTrials.gov; NCT02316821.
Kakavand B, Tsuda T, Centner A
… +2 more, Centner S, Maul T
Clin Auton Res
· 2025 Feb · PMID 39249159
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BACKGROUND: The autonomic nervous system (ANS) is critical in regulating involuntary bodily functions, including heart rate. Heart rate variability (HRV) reflects the complex interplay between the ANS and humoral factors...BACKGROUND: The autonomic nervous system (ANS) is critical in regulating involuntary bodily functions, including heart rate. Heart rate variability (HRV) reflects the complex interplay between the ANS and humoral factors, making it a valuable noninvasive tool for assessing autonomic function. While HRV has been extensively studied in adults, normative data for HRV in children, primarily based on long-term rhythm recordings, are limited. OBJECTIVE: This study aimed to establish comprehensive normative data for HRV in children. METHODS: In this retrospective study, we examined 24-h Holter monitors of children aged 1 day to 18 years, divided into six age groups, at Nemours Children's Health in Orlando, Florida, spanning the years 2013-2023. HRV analysis encompassed time-domain, frequency-domain, and nonlinear indices. RESULTS: Holter data for a total of 247 patients in six age groups were included. An age-related uptrend was observed in all time- and frequency-domain variables except the normalized unit of low-frequency power. Entropy analysis revealed contradictory results among different entropy techniques. Sample and approximate entropy analyses were consistent and showed less complexity and more predictability of HRV with decreasing heart rate, while Shannon entropy analysis showed the opposite. Fractal detrended fluctuation analysis exhibited significant decreases across the age groups, suggestive of diminishing self-similarity of HRV patterns. CONCLUSION: Control of heart rate and HRV is a highly complex process and requires further study for a better understanding. It seems that no single parameter can fully elucidate the entire process. A combination of time-domain, frequency-domain, and nonlinear indices may be necessary to explain HRV behavior in the growing body.
Delucenay-Clarke R, Niérat MC, Frugière A
… +3 more, Similowski T, Cayetanot F, Bodineau L
Clin Auton Res
· 2024 Aug · PMID 39133345
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Direct current stimulation (DCS) is a non-invasive approach to stimulate the nervous system that is now considered a powerful tool for treating neurological diseases such as those affecting cognitive or locomotor functio...Direct current stimulation (DCS) is a non-invasive approach to stimulate the nervous system that is now considered a powerful tool for treating neurological diseases such as those affecting cognitive or locomotor functions. DCS, as applied clinically today, is an approach built on early uses in antiquity and knowledge gained over time. Its current use makes use of specific devices and takes into account knowledge of the mechanisms by which this approach modulates functioning of the nervous system at the cellular level. Over the last 20 years, although there are few studies, it has been shown that DCS can also modulate the breathing autonomic function. In this narrative review, after briefly providing the historical perspective and describing the principles and the main cellular and molecular effects, we summarize the currently available data regarding the modulation of ventilation, and propose that DCS could be used to treat autonomic or non-autonomic neurological disorders affecting breathing.
Rahman S, Gamboa A, Saleem M
… +5 more, Kulapatana S, Diedrich A, Biaggioni I, Kirabo A, Shibao CA
Clin Auton Res
· 2024 Aug · PMID 39090323
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PURPOSE: Hypertension is one of the major causes of cardiovascular morbidity and mortality in the USA and disproportionately affects Black women. Endothelial-derived nitric oxide (eNO) substantially regulates blood press...PURPOSE: Hypertension is one of the major causes of cardiovascular morbidity and mortality in the USA and disproportionately affects Black women. Endothelial-derived nitric oxide (eNO) substantially regulates blood pressure in humans, and impaired NO-mediated vasodilation has been reported in the Black population. Previous studies using an NO synthase inhibitor, N-monomethyl-L-arginine (L-NMMA) did not fully determine the NO contribution to blood pressure because of baroreflex buffering. Therefore, in the present study we used trimethaphan, a ganglionic blocker, to inhibit baroreflex buffering and study NO modulation of blood pressure in Black women during L-NMMA infusion. METHODS: L-NMMA at doses of 250 μg/kg per minute was infused in combination with trimethaphan at doses of 4 mg/min to eliminate baroreflex mechanisms. Heart rate (HR) was obtained with continuous electrocardiogram monitoring, and continuous blood pressure was measured with the volume clamp method. The increase in systolic blood pressure (SBP) during both infusions was used to estimate the contribution of NO to blood pressure. RESULTS: Ten Black (age range 30-50 years, body mass index [BMI] 30-45 kg/m), and nine White women (age range 30-50 years, body mass index 30-45 kg/m) were enrolled in this study. During autonomic blockade, there was no difference in the decrease in SBP between Black and White women (- 20 ± 16.45 vs. - 24 ± 15.49 mm Hg, respectively; P = 0.659). When autonomic blockade was combined with L-NMMA, Black women had a significant increase in SBP compared to White women (54 ± 13.62 vs. 39 ± 09.64 mm Hg, respectively; P = 0.022, respectively). CONCLUSION: Autonomic blood pressure regulation was similar between Black and White women. However, NO contribution to blood pressure was significantly greater in Black women compared to White women. REGISTRATION: ClinicalTrials.gov: NCT01122407.
Clin Auton Res
· 2024 Aug · PMID 39039354
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PURPOSE: Memory plays an essential role in daily life and is one of the first functions to deteriorate in cognitive impairment and dementia. Transcutaneous vagus nerve stimulation (tVNS) is a promising therapeutic method...PURPOSE: Memory plays an essential role in daily life and is one of the first functions to deteriorate in cognitive impairment and dementia. Transcutaneous vagus nerve stimulation (tVNS) is a promising therapeutic method; however, its ability to enhance memory is underexplored, especially considering long-term stimulation. We aimed to investigate the effect of a 2-week course of auricular tVNS (taVNS) on memory in a non-clinical population. METHODS: This single-blind randomized placebo-wait-list controlled trial recruited 76 participants (30 men; mean age 48.32 years) and randomized them into four groups: early active/sham taVNS and late active/sham taVNS. Participation in the study lasted 4 weeks; early groups underwent 2 weeks intervention immediately following the first study site visit (days 0-13) and late groups 2 weeks after the first study site visit (days 14-27). Active and sham taVNS included 2 weeks of daily 4-h neurostimulation at the tragus or earlobe, respectively. To assess memory, we used the Rey Auditory Verbal Learning Test. RESULTS: Two weeks of active taVNS, but not sham taVNS, improved immediate recall and short-term memory score both in early and late groups. Furthermore, the improvements persisted over subsequent follow-up in early active taVNS. Importantly, the effect of active taVNS was superior to sham for immediate recall in both early and late groups. There were no statistical differences in delayed recall. CONCLUSION: Our findings suggest that taVNS has potential to improve memory, particularly immediate recall, and may be an effective method in preventing memory loss and mitigating cognitive aging.
Dell'Oro R, Quarti-Trevano F, Ciardullo S
… +3 more, Perseghin G, Mancia G, Grassi G
Clin Auton Res
· 2024 Aug · PMID 39037542
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PURPOSE: Clinical trials have shown that in type 2 diabetes mellitus (T2D) resting office heart rate (HR) values > 70 beats/minute are associated with an increased cardiovascular risk, a worse prognosis and an unfavorabl...PURPOSE: Clinical trials have shown that in type 2 diabetes mellitus (T2D) resting office heart rate (HR) values > 70 beats/minute are associated with an increased cardiovascular risk, a worse prognosis and an unfavorable outcome. The present study was aimed at investigating whether the above mentioned treshold HR values reflect a sympathetic overdrive of marked degree. METHODS: In 58 T2D patients (age range: 39-57 years) without signs of autonomic neuropathy and in 52 age-matched healthy controls, we assessed muscle sympathetic nerve activity (MSNA, microneurography) and venous plasma norepinephrine (NE, HPLC), subdividing the study population in different subgroups according to their clinic and 24-h HR values. RESULTS: In T2D progressively greater clinic and 24-h HR values were accompanied by progressive increases in MSNA and NE. HR cutoff values indicated by clinical trials as associated with an increased cardiovascular risk (> 70 beats/minute) were accompanied by MSNA values significantly higher than those detected in patients with lower HR, this being the case also for NE. In T2D both MSNA and NE were significantly related to clinic (r = 0.93, P < 0.0001 and r = 0.87, P < 0.0001, respectively) and 24-h (r = 0.92, P < 0.0001 and r = 0.84, P < 0.0001, respectively) HR. The MSNA and NE behaviour observed in T2D was not detected in healthy controls. CONCLUSIONS: In T2D clinic HR values allow to detect patients with a greater sympathetic overactivity. Considering the adverse clinical impact of the sympathetic overdrive on prognosis, our data emphasize the need of future studies investigating the potential usefulness of lifestyle and pharmacological interventions exerting sympathomodulatory effects.
Clin Auton Res
· 2024 Aug · PMID 39002040
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This is a self report. It is age related because I am 96 years old; about 5 years ago I was asymptomatic in this respect. I describe the difficulties to think to have to take a breath without getting evidence of hypoxia...This is a self report. It is age related because I am 96 years old; about 5 years ago I was asymptomatic in this respect. I describe the difficulties to think to have to take a breath without getting evidence of hypoxia such as flashes of light and other evidence of hypoxia such as loss of muscle tone. The problem I have is loss of autonomic function which normally controls breathing without the need to think to take a breath.
Clin Auton Res
· 2024 Aug · PMID 38980470
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PURPOSE: The goal of this manuscript was to review the biological and clinical evidence that serotonin neurotransmission might play an important role in the physiology and treatment of vasovagal syncope. METHODS: The au...PURPOSE: The goal of this manuscript was to review the biological and clinical evidence that serotonin neurotransmission might play an important role in the physiology and treatment of vasovagal syncope. METHODS: The authors reviewed PubMed and handsearches of secondary sources for papers related to the Bezold-Jarisch reflex and serotonin, the plausible involvement of the Bezold-Jarisch reflex in vasovagal syncope, and three lines of clinical evidence involving serotonin and the syncope. RESULTS: The Bezold-Jarisch reflex was first described following the infusion of veratrum alkaloids into animals in the 19th century. The reflex is triggered by serotonin stimulation chemoreceptors and mechanoreceptors in the the left ventricle. The afferent component of the reflex is carried by unmyelinated type C vagal nerve fibers, which results in parasympathetic efferent stimulation that causes bradycardia. The similarity of the combination of hypotension and bradycardia in the Bezold-Jarisch reflex and in vasovagal syncope led to the suggestion that the reflex was the cause of the syndrome. Three lines of evidence implicate the serotonin 5HT3 receptors in the heart in the reflex. There is genetic and physiologic evidence for the serotonin 5HT1A and 5HT3 receptors and the serotonin reuptake transporter (SERT). Acute blockade of SERT induces vasovagal syncope in humans undergoing head-up tilt table testing, and SERT inhibition reduces hypotension and bradycardia during spinal anaesthesia. Finally, three randomized clinical trials of SERT inhibitors uniformly reported that they significantly reduce the likelihood of vasovagal syncope recurrences. CONCLUSION: Multiple lines of evidence implicate serotonin neurotransmission in the cause of vasovagal syncope.
Kulapatana S, Diedrich A, Lersritwimanmaen P
… +1 more, Watanapa WB
Clin Auton Res
· 2024 Aug · PMID 38937334
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Postural orthostatic tachycardia syndrome (POTS) is a heterogeneous autonomic disorder. All patients have exaggerated tachycardia upon standing, but the pathophysiology may be diverse. We present a young adult Thai male...Postural orthostatic tachycardia syndrome (POTS) is a heterogeneous autonomic disorder. All patients have exaggerated tachycardia upon standing, but the pathophysiology may be diverse. We present a young adult Thai male with a chief complaint of palpitations while in an upright posture since childhood. The patient underwent a modified Ewing test battery which included standing test, deep breathing, and Valsalva maneuver. His heart rate increased more than 30 beats per minute (bpm) during repeated active stand tests (65 to 110 bpm and 77 to 108 bpm), while upright diastolic blood pressure increased more than 10 mmHg. Normal Valsalva ratio (2.01 and 1.86) and baseline heart rate variability (HF = 4030.24 ms and 643.92 ms) indicated intact vagal function. High low-frequency systolic blood pressure variability (LF = 20.93 mmHg), increased systolic blood pressure overshoot in phase IV of Valsalva (42 mmHg), and increased upright diastolic blood pressure indicated a hyperadrenergic state. In conclusion, the overall autonomic profile was compatible with hyperadrenergic POTS. Thus, we confirmed the first male POTS case reported in Thailand. We demonstrated the importance of autonomic function testing with continuous measurements to confirm POTS. There is a need for further research in POTS in Thailand.
Shoemaker LN, Sajid A, Schondorf R
… +1 more, Shoemaker JK
Clin Auton Res
· 2024 Jun · PMID 38926194
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PURPOSE: The compensatory mechanisms supporting cerebral perfusion throughout head-up tilt (HUT) in patients with vasovagal syncope (VVS) remain unclear. We tested the hypothesis that increased cerebrovascular compliance...PURPOSE: The compensatory mechanisms supporting cerebral perfusion throughout head-up tilt (HUT) in patients with vasovagal syncope (VVS) remain unclear. We tested the hypothesis that increased cerebrovascular compliance (Ci) and decreased cerebrovascular resistance (CVR) support cerebral blood velocity (CBV) during pre-syncope in VVS. METHODS: Finger arterial blood pressure (ABP) and right middle cerebral artery blood velocity (CBV) were recorded in 15 individuals diagnosed with VVS (n = 11 female, mean age: 40 ± 16 years, mean body mass index: 24.9 ± 4.0 kg/m) at supine rest and during HUT (80 degree angle). Individual ABP and CBV waveforms during VVS were input into a modified Windkessel model to calculate Ci and ohmic CVR. Gosling's pulsatility index (Pi; pulse amplitude/mean CBV) was calculated. RESULTS: Diastolic ABP, systolic ABP, mean ABP (72 ± 11 to 51 ± 12 mmHg), and CVR decreased progressively during presyncope (all P ≤ 0.04). As expected, systolic CBV was sustained (all P ≥ 0.29) while diastolic and mean CBV (51 ± 13 to 38 ± 13 mmHg) fell during presyncope (all P ≤ 0.04). Both Ci and Pi increased during presyncope (128 ± 97 and 60 ± 41%, respectively; all P ≤ 0.049) and were positively correlated (R = 0.79, P < 0.01). Increased Ci contributed to changes in mean CBV (P < 0.01) but decreased CVR did not (P = 0.28). CONCLUSIONS: These data provide evidence that Ci increases during presyncope in patients with VVS and is likely involved in the maintenance of systolic CBV during a fall in diastolic CBV. However, this regulation is not sufficient to preserve CBV in the presence of such extreme and progressive reductions in ABP.
Solinsky R, Burns K, Taylor JA
… +1 more, Singer W
Clin Auton Res
· 2024 Aug · PMID 38916658
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PURPOSE: This work's purpose was to quantify rapid sympathetic activation in individuals with spinal cord injury (SCI), and to identify associated correlations with symptoms of orthostatic hypotension and common autonomi...PURPOSE: This work's purpose was to quantify rapid sympathetic activation in individuals with spinal cord injury (SCI), and to identify associated correlations with symptoms of orthostatic hypotension and common autonomically mediated secondary medical complications. METHODS: This work was a cross-sectional study of individuals with SCI and uninjured individuals. Symptoms of orthostatic hypotension were recorded using the Composite Autonomic Symptom Score (COMPASS)-31 and Autonomic Dysfunction following SCI (ADFSCI) survey. Histories of secondary complications of SCI were gathered. Rapid sympathetic activation was assessed using pressure recovery time of Valsalva maneuver. Stepwise multiple linear regression models identified contributions to secondary medical complication burden. RESULTS: In total, 48 individuals (24 with SCI, 24 uninjured) underwent testing, with symptoms of orthostatic hypotension higher in those with SCI (COMPASS-31, 3.3 versus 0.6, p < 0.01; ADFSCI, 21.2 versus. 3.2, p < 0.01). Pressure recovery time was prolonged after SCI (7.0 s versus. 1.7 s, p < 0.01), though poorly correlated with orthostatic symptom severity. Neurological level of injury after SCI influenced pressure recovery time, with higher injury levels associated with more prolonged time. Stepwise multiple linear regression models identified pressure recovery time as the primary explanation for variance in number of urinary tract infections (34%), histories of hospitalizations (12%), and cumulative secondary medical complication burden (24%). In all conditions except time for bowel program, pressure recovery time outperformed current clinical tools for assessing such risk. CONCLUSIONS: SCI is associated with impaired rapid sympathetic activation, demonstrated here by prolonged pressure recovery time. Prolonged pressure recovery time after SCI predicts higher risk for autonomically mediated secondary complications, serving as a viable index for more "autonomically complete" injury.