Guerrero RVD, Vianna LC, Lehnen GCS
… +3 more, Daher M, Teixeira AL, Fernandes IA
Clin Auton Res
· 2025 Apr · PMID 39815060
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PURPOSE: Resting beat-to-beat blood pressure variability is a strong predictor of cardiovascular events and mortality. However, its underlying mechanisms remain incompletely understood. Given that the sympathetic nervous...PURPOSE: Resting beat-to-beat blood pressure variability is a strong predictor of cardiovascular events and mortality. However, its underlying mechanisms remain incompletely understood. Given that the sympathetic nervous system plays a pivotal role in cardiovascular regulation, we hypothesized that alpha-1 adrenergic receptors (the main sympathetic receptor controlling peripheral vasoconstriction) may contribute to resting beat-to-beat blood pressure variability. METHODS: Beat-to-beat heart rate (electrocardiography) and blood pressure (photoplethysmography) were continuously measured before and 2 h following, selective blockade of alpha-1 adrenergic receptors via oral administration of prazosin (1 mg/20 kg) in ten young healthy adults (two women). Cardiac output and total peripheral resistance were estimated using the ModelFlow method. RESULTS: Selective blockade of alpha-1 adrenergic receptors was confirmed by the marked reduction in the pressor response to intravenous infusion of phenylephrine hydrochloride (-80 ± 15%, P = 0.001 versus pre-prazosin). The blockade significantly decreased the standard deviation of the systolic (pre-prazosin versus post-prazosin: 5.6 ± 1.4 versus 3.8 ± 0.7 mmHg, P = 0.002), diastolic (3.2 ± 1.2 versus 2.2 ± 0.5 mmHg, P = 0.022), and mean blood pressure (3.7 ± 1.2 versus 2.5 ± 0.5 mmHg, P = 0.009), as well as total peripheral resistance (0.8 ± 0.5 versus 0.5 ± 0.1 mmHg/L/min, P = 0.047), but not cardiac output (521 ± 188 versus 453 ± 160 mL/min, P = 0.321). Similar results were found using different indices of variability. CONCLUSION: These findings indicate that alpha-1 adrenergic receptors play a significant role in regulating resting beat-to-beat blood pressure variability in young, healthy adults.
de Lange FJ, van Zanten S, Rivasi G
… +10 more, Groppelli A, Russo V, Maggi R, Capacci M, Nawaz S, Comune A, Ungar A, Parati G, Brignole M, Fedorowski A
Clin Auton Res
· 2025 Jun · PMID 39718670
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AIM: The study aimed to assess the haemodynamic effects of fludrocortisone and midodrine, alone or combined, in patients with recurrent syncope and/or symptoms due to hypotension and ≥ 1 daytime systolic blood pressure (...AIM: The study aimed to assess the haemodynamic effects of fludrocortisone and midodrine, alone or combined, in patients with recurrent syncope and/or symptoms due to hypotension and ≥ 1 daytime systolic blood pressure (SBP) drop < 90 mmHg or ≥ 2 daytime SBP drops < 100 mmHg recorded by 24-h ambulatory blood pressure monitoring (ABPM1). METHOD: A total of 53 patients (mean age, 40.9 ± 18.5 years, 37 female) were treated with fludrocortisone (0.05-0.2 mg per day) and/or midodrine (2.5-10 mg two or three times per day). A second ABPM (ABPM2) was performed within 6 months and the results of ABPM1 AND ABPM2 were compared to assess the effects of BP-rising drugs. RESULTS: In 32 patients assigned to fludrocortisone, 24-h SBP increased from 107.1 ± 9.9 mmHg to 116.3 ± 14.9 (p = 0.0001), the number of daily SBP drops < 90 mmHg decreased by 73% (p = 0.0001) and that of drops < 100 mmHg decreased by 41% (p = 0.0005). In 14 patients assigned to midodrine, 24-h SBP increased from 112.7 ± 7.4 mmHg to 115.0 ± 9.1 (p = 0.12), the number of daily SBP drops < 90 mmHg decreased by 52% (p = 0.04) and that of drops < 100 mmHg decreased by 34% (p = 0.007). In the seven patients taking both fludrocortisone and midodrine, 24-h SBP increased from 110.1 ± 11.5 mmHg to 114.0 ± 12.4 (p = 0.002), the number of daily SBP drops < 90 mmHg decreased by 69% (p = 0.22) and that of drops < 100 mmHg decreased by 44% (p = 0.04). CONCLUSIONS: Both fludrocortisone and midodrine effectively increased 24-h SBP and reduced SBP drops on ABPM but fludrocortisone seemed to be more effective than midodrine. Further randomised studies are needed to confirm these observations.
Clin Auton Res
· 2025 Feb · PMID 39692954
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PURPOSE: The parasympathetic effects of the sphenopalatine ganglion (SPG) on the cerebral vasculature provide a compelling rationale for its therapeutic application in cerebrovascular ischemia. In recent years, attempts...PURPOSE: The parasympathetic effects of the sphenopalatine ganglion (SPG) on the cerebral vasculature provide a compelling rationale for its therapeutic application in cerebrovascular ischemia. In recent years, attempts have been made to stimulate the SPG to achieve beneficial effects on cerebral circulation. METHODS: This review synthesizes the available publications on SPG stimulation. It critically evaluates the evidence from preclinical studies and clinical trials to assess its potential as a treatment for acute cerebrovascular disorders and outlines aspects that still require more study. RESULTS: The medical literature provides consistent evidence of the significant effects of stimulating the SPG on cerebrovascular circulation. In addition, considerable evidence supports the therapeutic role of SPG stimulation in patients with cerebral ischemia. CONCLUSION: Given the current understanding, future research could explore the potential of SPG stimulation as a non-reperfusion intervention to improve long-term outcomes for individuals with ischemic cerebrovascular conditions.
Sorola S, Hyrylä V, Eronen T
… +5 more, Kupari S, Venojärvi M, Tikkanen H, Tarvainen M, Lindholm H
Clin Auton Res
· 2025 Jun · PMID 39681809
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PURPOSE: Cardiovascular autonomic neuropathy remains underdiagnosed in type 1 diabetes mellitus, posing a risk for severe complications, particularly in patients with lowered V̇O, compared to controls. This study aimed t...PURPOSE: Cardiovascular autonomic neuropathy remains underdiagnosed in type 1 diabetes mellitus, posing a risk for severe complications, particularly in patients with lowered V̇O, compared to controls. This study aimed to determine whether heart rate variability during cardiovascular autonomic reflex tests reveals early signs of cardiovascular autonomic neuropathy in patients with uncomplicated type 1 diabetes mellitus and normal cardiovascular fitness, compared to healthy controls. METHODS: A type 1 diabetes mellitus group (n = 14) with no other diagnosed diseases (diabetes duration 15 ± 7 years) and a control group (n = 31) underwent deep breathing test, passive orthostatic test, and cardiopulmonary exercise test. Participants were assessed for heart rate variability, heart rate, blood pressure, and V̇O (mL/min/kg). RESULTS: Participant characteristics, including V̇O (mL/min/kg), showed no significant differences. The type 1 diabetes mellitus group had higher systolic blood pressure during the supine phase of the orthostatic test than healthy controls (131.6 ± 14.7 mmHg vs. 122.4 ± 10.8 mmHg, p = 0.022). After 5 mins in the upright position, systolic blood pressure (132.2 ± 20.6 mmHg vs. 118.7 ± 11.7 mmHg, p = 0.036), heart rate (85 (76; 89) bpm vs. 75 (72; 83) bpm, p = 0.013), and the root mean square of successive RR interval differences (20.22 (11.22; 27.42) vs. 27.11 (19.90; 35.52), p = 0.033) were significantly different compared to controls. CONCLUSION: Patients with uncomplicated type 1 diabetes mellitus, despite having normal cardiorespiratory fitness, exhibited higher systolic pressure and greater sympathetic activation in orthostatic tests, suggesting subclinically altered cardiovascular autonomic function.
Treadwell JR, Wagner J, Reston JT
… +3 more, Phillips T, Hedden-Gross A, Tipton KN
Clin Auton Res
· 2025 Feb · PMID 39658729
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PURPOSE: For Long COVID autonomic dysfunction, we have summarized published evidence on treatment effectiveness, clinical practice guidelines, and unpublished/ongoing studies. METHODS: We first interviewed 11 stakeholder...PURPOSE: For Long COVID autonomic dysfunction, we have summarized published evidence on treatment effectiveness, clinical practice guidelines, and unpublished/ongoing studies. METHODS: We first interviewed 11 stakeholders (clinicians, clinician/researchers, payors, patient advocates) to gain clinical insights and identify key areas of focus. We searched Embase, CINAHL, Medline, PsycINFO, and PubMed databases for relevant English-language articles published between 1 January 2020 and 30 April 2024. We also searched several other resources for additional relevant guidelines (e.g., UpToDate) and unpublished/ongoing studies (e.g., the International Clinical Trials Registry Platform). All information was summarized narratively. RESULTS: We included 11 effectiveness studies that investigated numerous treatment regimens (fexofenadine + famotidine, maraviroc + pravastatin, selective serotonin reuptake inhibitors, nutraceutical formulations, multicomponent treatments, heart rate variability biofeedback, inspiratory muscle training, or stellate ganglion block). One randomized trial reported benefits of a nutraceutical (SIM01) on fatigue and gastrointestinal upset. The 11 guidelines and position statements addressed numerous aspects of treatment, but primarily exercise/rehabilitation, fluid/salt intake, and the use of compression garments. The 15 unpublished/ongoing studies are testing nine different interventions, most prominently ivabradine and intravenous immunoglobulin. CONCLUSION: Existing studies on the treatment of Long COVID autonomic dysfunction are often small and uncontrolled, making it unclear whether the observed pre-post changes were due solely to the administered treatments. Guidelines display some overlap, and we identified no direct contradictions. Unpublished/ongoing studies may shed light on this critical area of patient management.
Clin Auton Res
· 2025 Apr · PMID 39656385
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BACKGROUND: Autonomic synucleinopathies feature autonomic failure and intracellular deposition of the protein alpha-synuclein. Three such conditions are the Lewy body diseases (LBDs) Parkinson's disease (PD) and pure aut...BACKGROUND: Autonomic synucleinopathies feature autonomic failure and intracellular deposition of the protein alpha-synuclein. Three such conditions are the Lewy body diseases (LBDs) Parkinson's disease (PD) and pure autonomic failure (PAF) and the non-LBD synucleinopathy multiple system atrophy (MSA). These diseases all entail catecholaminergic abnormalities in the brain, sympathetically innervated organs, or both; however, little is known about renal catecholaminergic functions in autonomic synucleinopathies. We measured urinary excretion rates of the sympathetic neurotransmitter norepinephrine, the hormone epinephrine, the autocrine-paracrine substance dopamine, the catecholamine precursor 3,4-dihydroxyphenylalanine (DOPA), 3,4-dihydroxyphenylglycol (DHPG, the main neuronal metabolite of norepinephrine), and 3,4-dihydroxyphenylacetic acid (DOPAC, a major dopamine metabolite), in PD, PAF, and MSA groups and controls. METHODS: Data were reviewed from all research participants who had urine collections (usually 3.5 h) at the National Institutes of Health (NIH) Clinical Center from 1995 to 2024. The control cohort had neither autonomic failure nor a movement disorder. RESULTS: Norepinephrine excretion rates were decreased compared with controls in PD (p = 0.0001), PAF (p < 0.0001), and MSA (p < 0.0001). Dopamine excretion was also decreased in the three groups (PD: p = 0.0136, PAF: p = 0.0027, MSA: p = 0.0344). DHPG excretion was decreased in PD (p = 0.0004) and PAF (p = 0.0004) but not in MSA. DOPA and epinephrine excretion did not differ among the study groups. CONCLUSIONS: Autonomic synucleinopathies involve decreased urinary excretion rates of norepinephrine and dopamine. Since virtually all of urinary dopamine in humans is derived from circulating DOPA, the low rates of urinary norepinephrine and dopamine excretion may reflect dysfunctions in the renal sympathetic noradrenergic system, the DOPA-dopamine autocrine-paracrine system, or both systems.
Galli S, De Carolis L, Bianchini E
… +6 more, Alborghetti M, Caliò B, Pacilio P, Fanciulli A, Pontieri FE, Rinaldi D
Clin Auton Res
· 2025 Apr · PMID 39633032
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PURPOSE: Autonomic failure has a major impact on the quality of life of individuals with Parkinson's disease (PD), especially in advanced stages of the disease. Levodopa/carbidopa intestinal gel (LCIG) infusion is a well...PURPOSE: Autonomic failure has a major impact on the quality of life of individuals with Parkinson's disease (PD), especially in advanced stages of the disease. Levodopa/carbidopa intestinal gel (LCIG) infusion is a well-established treatment for advanced PD with severe motor fluctuations and provides substantial benefit in managing some non-motor symptoms (NMS), such as sleep, fatigue, and neuropsychiatric issues. The effect of LCIG on autonomic symptoms is by contrast not well known. Here we performed a systematic review on the influence of LCIG therapy on autonomic dysfunction in PD individuals. METHODS: Following the PRISMA guidelines, we systematically searched for studies that included autonomic outcome measures in LCIG-treated PD individuals, limiting the search to articles written in English and published between January 2005 and June 2023. We evaluated improvement, stability, or worsening of gastrointestinal, urinary, and cardiovascular symptoms at six different timepoints according to clinimetric scale changes compared to baseline. Data on autonomic adverse events (AEs) possibly related to LCIG treatment were also collected. RESULTS: Of the 1476 studies identified in the initial search, 16 ultimately met the inclusion criteria and underwent quality assessment and data extraction, with data from 1361 PD patients (18.3 months mean follow-up). Thirteen studies reported improvement or stability of gastrointestinal, urinary, and cardiovascular symptoms over the interventional period. One study found a worsening of cardiovascular symptoms and two of urological symptoms. Regarding safety, seven studies reported gastrointestinal (8.4%), urinary (0.5%), and cardiovascular (1.1%) autonomic LCIG-related AEs. CONCLUSIONS: LCIG infusion may help to reduce the burden of autonomic symptoms in advanced PD. Prospective studies specifically addressing the effect of LCIG on autonomic function in advanced PD are warranted.
Debs R, Diene G, Cortadellas J
… +4 more, Molinas C, Kermorgant M, Tauber M, Pavy Le Traon A
Clin Auton Res
· 2025 Apr · PMID 39633031
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PURPOSE: Prader-Willi syndrome (PWS) is a rare genetic neurodevelopmental condition characterized by cognitive disabilities, behavioral problems, hypothalamic dysfunction with obesity, and sleep disorders. A few studies...PURPOSE: Prader-Willi syndrome (PWS) is a rare genetic neurodevelopmental condition characterized by cognitive disabilities, behavioral problems, hypothalamic dysfunction with obesity, and sleep disorders. A few studies have reported autonomic nervous system dysfunction. Our aim was to investigate dysautonomia by combining sleep studies and standard autonomic testing in regularly followed children with PWS. METHODS: In this retrospective study, heart rate variability was analyzed during each sleep stage (polysomnography) using time and frequency domains in PWS children (N = 37) compared with age-matched controls (N = 20). Cardiovascular autonomic testing (Ewing tests) and sweating assessment (electrochemical skin conductance) were also performed in patients over 6 years (N = 23). RESULTS: Autonomic testing: Heart rate changes with active standing and with deep breathing were impaired in 47% and 22% of the children, respectively. Asymptomatic orthostatic hypotension (OH) was found in 26%. Baroreflex sensitivity in supine position was in normal range (14.1 ± 6.7 ms/mmHg). Electrochemical skin conductance was normal. Sleep study: 46% of the children with PWS had obstructive sleep apnea and 24% had central sleep apnea. None of these events were observed in the control group. Mean R-R and time domain heart rate variability parameters were significantly lower compared with controls in N2 and Rapid Eye Movement (REM) sleep stages. Narcoleptic-like phenotype was found in 47% associated with lower low-frequency (LF) power (sympathetic index) in REM sleep. CONCLUSION: Our study confirms a decreased vagal modulation during both wakefulness and sleep in children with PWS. OH in some patients suggests a sympathetic dysfunction. These changes may contribute to the increased cardiovascular risk in PWS.
Kulapatana S, Urechie V, Rigo S
… +8 more, Mohr A, Vance YA, Okamoto LE, Gamboa A, Shibao C, Biaggioni I, Furlan R, Diedrich A
Clin Auton Res
· 2025 Apr · PMID 39614968
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PURPOSE: The semiautomated carbon monoxide (CO) rebreathing method has been introduced as a noninvasive and radiation-free blood volume estimation method. We tested whether the semiautomated CO rebreathing method can det...PURPOSE: The semiautomated carbon monoxide (CO) rebreathing method has been introduced as a noninvasive and radiation-free blood volume estimation method. We tested whether the semiautomated CO rebreathing method can detect the blood volume deficit in postural orthostatic tachycardia syndrome (POTS). In addition, we explored the relationship between blood volume estimated from CO rebreathing and body impedance. PATIENTS AND METHODS: We recruited 53 subjects (21 female patients with POTS, 19 healthy female participants, and 13 healthy male participants) to record blood volumes and hemodynamic data. Blood volumes were measured by CO rebreathing and segmental body impedance. Linear regression models to predict normal values of red blood cell volume (RBCV), plasma volume (PV), and total blood volume (BV) were developed. Percentage deviations from the predicted normal volumes were calculated. RESULTS: Patients with POTS had lower RBCV (25.18 ± 3.95 versus 28.57 ± 3.68 mL/kg, p = 0.008, patients with POTS versus healthy female participants), BV (64.53 ± 10.02 versus 76.78 ± 10.00 mL/kg, p < 0.001), and BV deviation (-13.92 ± 10.38% versus -0.02 ± 10.18%, p < 0.001). Patients with POTS had higher supine heart rate (HR) (84 ± 14 versus 69 ± 11 bpm, p < 0.001) and upright HR (123 ± 23 versus 89 ± 22 bpm, p < 0.001). We found a correlation between BV deviation and upright HR in patients with POTS (r = -0.608, p = 0.003), but not in healthy participants. Volumes from the CO rebreathing and body impedance were well correlated (r = 0.629, p < 0.001). CONCLUSIONS: The CO rebreathing method can detect BV deficit, as well as the RBCV deficit in patients with POTS. The negative correlation between BV deviation and upright HR indicates that hypovolemia is one of the pathophysiological causes of POTS. Correlations between body impedance and CO rebreathing volume suggest its usefulness for measurements of volume changes.
Warnakulasuriya T, George B, Lever N
… +1 more, Ramchandra R
Clin Auton Res
· 2025 Apr · PMID 39601940
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PURPOSE: The use of circulatory assist devices has been shown to improve glomerular filtration rate and reduce the incidence of acute kidney injury in patients following acute cardiac pathology. However, the mechanisms o...PURPOSE: The use of circulatory assist devices has been shown to improve glomerular filtration rate and reduce the incidence of acute kidney injury in patients following acute cardiac pathology. However, the mechanisms of improvement in kidney function are not clear. We tested the hypothesis that mechanical circulatory support would result in a decrease in directly recorded renal sympathetic nerve activity (RSNA) and mediate the improvement in renal blood flow (RBF) in a setting of acute myocardial infarction (AMI)-induced left ventricular systolic dysfunction. METHODS: An anaesthetized ovine model was used to induce AMI (n = 8) using injections of microspheres into the left coronary artery in one group. The second group did not undergo embolization (n = 6). The effects of mechanical circulatory support using the Impella CP on directly recorded renal sympathetic nerve activity were examined in these two groups of animals. RESULTS: Injection of microspheres resulted in a drop in mean arterial pressure (MAP) of 21 ± 4 mmHg compared to baseline values (p < 0.05; n = 8). This was associated with a 67% increase in renal sympathetic nerve activity (RSNA; from 16 ± 5 to 21 ± 5 spikes/s; p < 0.05; n = 7). Impella CP support significantly increased MAP by 13 ± 1.5 mmHg at pump level 8 (p < 0.05) in the AMI group. Incremental pump support resulted in a significant decrease in RSNA (p < 0.05) in both groups. At pump level P8 in the AMI group, RSNA was decreased by 21 ± 5.5% compared to pump level P0 when the pump was not on. CONCLUSION: Our data indicate that the improvement in kidney function following mechanical circulatory support may be mediated in part by renal sympathoinhibition.
Clin Auton Res
· 2025 Apr · PMID 39592549
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PURPOSE: We compared standing and upright tilt in patients with postural tachycardia syndrome (POTS) and healthy volunteers to determine whether standing accurately tests for POTS in youngsters < 19 years. POTS in adoles...PURPOSE: We compared standing and upright tilt in patients with postural tachycardia syndrome (POTS) and healthy volunteers to determine whether standing accurately tests for POTS in youngsters < 19 years. POTS in adolescents is defined by orthostatic intolerance plus sustained excessive upright tachycardia, without hypotension during upright tilt. We examined whether active standing is a valid classifier for POTS in adolescents compared to tilt. METHODS: Patients with POTS (N = 36, 12.2-18.8 years) and healthy volunteers (N = 39, 13.1-18.9 years) performed stand for a minimum of 5-min and were tilted to 70° for 10 min. Receiver operating characteristics analyses (ROC) were performed at 5-min stand, and at 5 and 10 min tilt for optimal threshold for heart rate (HR) increase (ΔHR), and test sensitivity and specificity. RESULTS: Most subjects were unable to stand for 10 min. ΔHRs at 5 min stand were higher in POTS (31 ± 3) compared with control (21 ± 2) and elevated at 5- or 10-min tilt in POTS (51 ± 3 and 51 ± 2) versus control (26 ± 2 and 25 ± 2) compared with standing. ΔHR in POTS and controls for 10 min were not different from 5 min. For 5 min stand ROC threshold was 26 beats per min (bpm), sensitivity of 70.6%, and specificity of 68.2% compared with 39 bpm, 88.2%, and 95.1% for 5 min tilt, and 40 bpm, 94.1%, and 95.1% for 10-min tilt. A precision-recall graph confirmed the superior discriminating ability of 5 min and 10 min tilt compared to 5 min stand. CONCLUSIONS: The stand test is relatively non-specific and imprecise compared to tilt and does not satisfactorily distinguish POTS from control in patients aged < 19 years old.