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Applied Psychophysiology and Biofeedback May 2024Orthostatic hypotension (OH) is a form of orthostatic intolerance (OI) and a key physiological indicator of autonomic dysfunction that is associated with an increased...
Orthostatic hypotension (OH) is a form of orthostatic intolerance (OI) and a key physiological indicator of autonomic dysfunction that is associated with an increased risk of major cerebrocardiovascular events. Symptoms of cerebral hypoperfusion have been reported in patients with OH, which worsens symptoms and increases the risk of syncope. Since pharmacological interventions increase blood pressure (BP) independent of posture and do not restore normal baroreflex control, nonpharmacological treatments are considered the foundation of OH management. While reductions in cerebral blood flow velocity (CBF) during orthostatic stress are associated with a decrease in end-tidal CO (EtCO) and hypocapnia in patients with OI, their contribution to the severity of OH is not well understood. These measures have been physiological targets in a wide variety of biofeedback interventions. This study explored the relationship between cardiovascular autonomic control, EtCO and cerebral hypoperfusion in patients (N = 72) referred for OI. Patients with systolic OH were more likely to be male, older, demonstrate reduced adrenal and vagal baroreflex sensitivity, and reduced cardiovagal control during head-up tilt (HUT) than patients without systolic OH. Greater reduction in CBF during HUT was associated with a larger reduction in ETCO and systolic BP during HUT. While deficits in cardiovascular autonomic control played a more important role in systolic OH, reduced EtCO was a major contributor to orthostatic cerebral hypoperfusion. These findings suggest that biofeedback treatments targeting both the autonomic nervous system and EtCO should be part of nonpharmacological interventions complementing the standard of care in OH patients with symptoms of cerebral hypoperfusion.
PubMed: 38809485
DOI: 10.1007/s10484-024-09646-1 -
Journal of Neurology May 2024Autonomic dysfunction is common and disabling in Parkinson's disease (PD). The effects of deep brain stimulation (DBS) on the cardiovascular system in PD remain poorly... (Review)
Review
BACKGROUND
Autonomic dysfunction is common and disabling in Parkinson's disease (PD). The effects of deep brain stimulation (DBS) on the cardiovascular system in PD remain poorly understood. We aimed to assess the effect of DBS on cardiovascular symptoms and objective measures in PD patients.
METHODS
We conducted a systematic literature search in PubMed/MEDLINE.
RESULTS
36 out of 472 studies were included, mostly involving DBS of the subthalamic nucleus, and to a lesser extent the globus pallidus pars interna and pedunculopontine nucleus. Seventeen studies evaluated the effect of DBS on patient-reported or clinician-rated cardiovascular symptoms, showing an improvement in the first year after surgery but not with longer-term follow-up. DBS has no clear direct effects on blood pressure during an orthostatic challenge (n = 10 studies). DBS has inconsistent effects on heart rate variability (n = 10 studies).
CONCLUSION
Current evidence on the impact of DBS on cardiovascular functions in PD is inconclusive. DBS may offer short-term improvement of cardiovascular symptoms in PD, particularly orthostatic hypotension, which may be attributed to dopaminergic medication reduction after surgery. There is insufficient evidence to draw conclusions on the direct effect of DBS on blood pressure and heart rate variability.
PubMed: 38809271
DOI: 10.1007/s00415-024-12459-1 -
Health Science Reports May 2024The nonmotor symptoms (NMS) of Parkinson's disease (PD) and their potential role in early diagnosis are recent debates. Herein, we aimed to investigate the association...
BACKGROUND AND AIMS
The nonmotor symptoms (NMS) of Parkinson's disease (PD) and their potential role in early diagnosis are recent debates. Herein, we aimed to investigate the association between depression and NMS of PD including sleep disorders, hyposexuality, hyposmia, constipation, and orthostatic hypotension.
METHODS
A total of 93 PD patients with depression and 67 PD patients without depression were included in the study, and NMS were compared between the two groups. Furthermore, the possible associations between depression severity measured by Beck Depression Inventory (BDI) and NMS were investigated using linear regression or binary logistic regression models controlled for possible confounders. Eventually, we performed a subgroup analysis in each mild, moderate, and severe depression group.
RESULTS
Orthostatic hypotension, constipation, and hyposexuality showed a significant difference between PD patients with and without depression ( < 0.001, = 0.029, and < 0.001, respectively). The BDI score was significantly associated with hyposexuality, Montreal cognitive assessment (MoCA), and Pittsburgh Sleep Quality ( = 0.016, = 0.010, and = 0.011, respectively); however, after adjustments for possible confounders, the associations of the BDI score with the MoCA score and hyposexuality remained significant ( = 0.015 and = 0.019, respectively). Considering subgroup analysis, a similar pattern of significant results was observed particularly in the severe group.
CONCLUSIONS
This study suggests a possible association between depression in PD patients and some NMS observed in the course of PD. These findings could be beneficial for early diagnosis of the disease, which eventually could make a considerable difference in the management of PD patients. Additional interventional longitudinal studies are warranted to explore how controlling depression could impact the NMS of patients with PD.
PubMed: 38803654
DOI: 10.1002/hsr2.2106 -
Cureus Apr 2024Background While the effects of exercise on the cardiovascular system are well documented, ultra-endurance sports involve distances beyond the scope of traditional...
Background While the effects of exercise on the cardiovascular system are well documented, ultra-endurance sports involve distances beyond the scope of traditional marathons and have grown in popularity at a staggering pace in recent years. While short-term high-intensity exercise stimulates sympathetic rises in heart rate (HR) and blood pressure (BP), the depletion of fluid and electrolyte reserves characteristic of ultra-endurance sports may contribute to decreases in overall BP after the race. If decompensation of the autonomic safety net occurs, orthostatic hypotension as a result of fluid loss during an event may cause fatigue, dizziness, syncope, or collapse. Methodology Subjects were recruited by emails sent to race participants and at pre-race meetings, and no participants were excluded from the study. We observed BP and HR changes in subjects before and after ultramarathon activity in both supine and standing positions over multiple races of variant length and terrain from 50 to 240 km from 2013 to 2018. Participants entered races in Florida, with a mean age of 43.8 and an average body mass index (BMI) of 21.2. In addition to pre-race and post-race measurements, positional post-race BPs and HRs were analyzed for orthostatic trends. Results Of those who participated, 140 completed the events and post-race HR and BP measurements were recorded. The mean systolic blood pressure (SBP) increase from pre-race to post-race standing was 21 mmHg, while the mean diastolic blood pressure (DBP) rise was 13 mmHg. While in a supine position, there was a 15 mmHg increase in SBP from pre-race to post-race, along with a 7 mmHg rise in diastolic pressure. Post-race supine to standing average BP change was insignificant. In the supine position, the mean HR increased by 20 beats per minute (bpm) after the race and by 27 bpm while standing. After the race, the average increase in HR supine to standing was 15 bpm. Conclusions The SBP changed much more notably than diastolic pressures likely due to the increase in stroke volume associated with the sympathetic response during exercise. HR values also climbed as a result of exercise stress in the setting of catecholamine release, and the combined influence contributed to increased cardiac output despite water and electrolyte loss during the event. Post-race, no trends of orthostatic hypotension were noted either with HR or BP when rising from a supine position. The significance of the contribution of fluid intake during the race to compensatory mechanisms under neural control requires further study.
PubMed: 38800277
DOI: 10.7759/cureus.58923 -
Journal of Alzheimer's Disease : JAD 2024Higher blood pressure variability (BPV) predisposes to cognitive decline. To investigate underlying mechanisms, we measured 24-h ambulatory BPV, nocturnal dipping and...
Higher blood pressure variability (BPV) predisposes to cognitive decline. To investigate underlying mechanisms, we measured 24-h ambulatory BPV, nocturnal dipping and orthostatic hypotension in 518 participants with vascular cognitive impairment, carotid occlusive disease, heart failure, or reference participants. We determined cross-sectional associations between BPV indices and plasma biomarkers of neuronal injury (neurofilament light chain) and Alzheimer's disease (phosphorylated-tau-181 and Aβ42/Aβ40). None of the BPV indices were significantly associated with any of the biomarkers. Hence, in patients with diseases along the heart-brain axis, we found no evidence for an association between BPV and selected markers of neuronal injury or Alzheimer's disease.
Topics: Humans; Alzheimer Disease; Male; Female; Aged; Biomarkers; Blood Pressure; Amyloid beta-Peptides; Cross-Sectional Studies; tau Proteins; Middle Aged; Peptide Fragments; Neurofilament Proteins; Brain; Hypotension, Orthostatic; Heart Failure; Aged, 80 and over
PubMed: 38788076
DOI: 10.3233/JAD-240119 -
Nephrology, Dialysis, Transplantation :... May 2024Volenrelaxin, is a half-life-extended recombinant human relaxin protein developed for improving kidney perfusion and cardiorenal function. This study assessed the...
BACKGROUND AND HYPOTHESIS
Volenrelaxin, is a half-life-extended recombinant human relaxin protein developed for improving kidney perfusion and cardiorenal function. This study assessed the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of volenrelaxin following single- and multiple-ascending doses (SAD and MAD) administration.
METHODS
In this Phase 1, 4-part, randomized, double-blinded, placebo-controlled SAD and MAD study in healthy participants, SAD participants (n = 56) received an intravenous (IV) or subcutaneous (SC) dose of volenrelaxin or placebo in a dose-ascending manner. MAD participants (n = 77) received volenrelaxin or placebo SC once weekly for 5 weeks. Effective renal plasma flow (ERPF) and measured glomerular filtration rate (mGFR) were determined by para-aminohippurate and iohexol clearance, respectively.
RESULTS
Volenrelaxin demonstrated an extended half-life and increased acute and chronic placebo-adjusted ERPF change from baseline by 50% and 44%, respectively (p < 0.0001). Measured GFR was unchanged, while filtration fraction and afferent/efferent renal arteriolar resistances were reduced. Systolic and diastolic blood pressures decreased, and pulse rate increased with increasing volenrelaxin exposures, demonstrating maximal model-derived placebo-adjusted changes (90% confidence interval) of -6.16 (-8.04, -4.28) mmHg, -6.10 (-7.61, -4.58) mmHg, and + 4.39 (3.38, 5.39) bpm, respectively. Adverse events were mild, with no difference in orthostatic hypotension between volenrelaxin and placebo.
CONCLUSION
Volenrelaxin was well-tolerated, safe and suitable for weekly SC dosing. Volenrelaxin showed a sustained improvement in kidney perfusion upon repeated dosing, supporting further clinical development in chronic kidney disease and chronic heart failure. Clinical trial registration: NCT04768855.
PubMed: 38782726
DOI: 10.1093/ndt/gfae112 -
Endocrine Practice : Official Journal... May 2024Hypermetabolic state in Graves' disease (GD) has a great impact on heart homeostasis, acting directly on the heart muscle and modulating the autonomic nervous system. To...
OBJECTIVES
Hypermetabolic state in Graves' disease (GD) has a great impact on heart homeostasis, acting directly on the heart muscle and modulating the autonomic nervous system. To characterize cardiac autonomic neuropathy (CAN) as a possible complication in patients with GD.
METHODS
We evaluated euthyroid GD patients and a control group of healthy euthyroid people. CAN was assessed using autonomic tests of cardiovascular reflex and heart rate variability: respiratory, Valsalva, orthostatic and orthostatic hypotension tests, high frequency, low frequency, and very low-frequency bands. Transthoracic echocardiography was performed in GD patients.
RESULTS
Sixty GD patients and 50 people in control group were assessed. CAN was diagnosed in 20% of GD and 14% in the control group. Among GD, 13.3% presented incipient, and 6.7% established CAN, while in the control group, it was verified incipient in 8% and established in 6% (P = .7479). All GD patients with CAN presented an alteration in the deep breathing test. Age and smoking were evidenced as factors associated with the presence of CAN, while higher TRAb values at diagnosis decreased the chance of CAN.
CONCLUSIONS
The prevalence of CAN in euthyroid GD patients was 20%. Changes in the cardiac autonomic nervous system were identified, pointing to the importance of evaluating this complication in these patients. Smoking was a predictive factor for CAN, increasing its relationship with conditions that aggravate GD.
PubMed: 38777033
DOI: 10.1016/j.eprac.2024.05.010 -
Experimental Gerontology Aug 2024Orthostatic hypotension (OH) is common in older adults with hypertension. Antihypertensive treatment (AHT) prevents cardio- and cerebrovascular events. However,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Orthostatic hypotension (OH) is common in older adults with hypertension. Antihypertensive treatment (AHT) prevents cardio- and cerebrovascular events. However, physicians are concerned to cause OH, making them hesitant to initiate or augment AHT in older adults with hypertension.
METHODS
We systematically researched electronic databases for trials with older participants (≥65 years) with hypertension and OH assessment after initiating, discontinuing, or augmenting AHT. Study quality was assessed using the ROBINS-I tool. Meta-analyses on OH prevalence and postural blood pressure (BP) drop were performed.
RESULTS
Twenty-five studies (26,695 participants) met inclusion criteria, of which fifteen could be included in the meta-analyses. OH prevalence decreased after AHT initiation or augmentation (risk ratio 0.39 (95 % CI = 0.21-0.72; I = 47 %; p < 0.01), n = 6 studies), but also after AHT discontinuation (risk ratio 0.39 (95 % CI = 0.28-0.55; I = 0 %; p < 0.01), n = 2 studies). Postural BP drop did not change after initiation or augmentation of AHT (mean difference 1.07 (95 % CI = -0.49-2.64; I = 92 %; p = 0.18), n = 11 studies). The main reason for ten studies not to be included in the meta-analyses was absence of baseline OH data. Most of these studies reported OH incidences between 0 and 2 %. Studies were heterogeneous in OH assessment methods (postural change, timing of BP measurements, and OH definition). Risk of bias was moderate to serious in twenty studies.
CONCLUSION
Results suggest that AHT initiation or augmentation decreases OH prevalence, implying that the risk of inducing OH may be overestimated in current AHT decision-making in older adults. However, the overall low level of evidence and the finding that AHT discontinuation reduces OH prevalence limit firm conclusions at present and highlight an important research gap. Future AHT trials in older adults should measure OH in a standardized protocol, adhering to consensus guidelines to overcome these limitations.
Topics: Aged; Aged, 80 and over; Humans; Antihypertensive Agents; Blood Pressure; Hypertension; Hypotension, Orthostatic; Prevalence
PubMed: 38772447
DOI: 10.1016/j.exger.2024.112461 -
Hypertension (Dallas, Tex. : 1979) Jul 2024The NET (norepinephrine transporter) is situated in the prejunctional plasma membrane of noradrenergic neurons. It is responsible for >90% of the norepinephrine uptake... (Review)
Review
The NET (norepinephrine transporter) is situated in the prejunctional plasma membrane of noradrenergic neurons. It is responsible for >90% of the norepinephrine uptake that is released in the autonomic neuroeffector junction. Inhibitors of this cell membrane transporter, known as norepinephrine reuptake inhibitors (NRIs), are commercially available for the treatment of depression and attention deficit hyperactivity disorder. These agents increase norepinephrine levels, potentiating its action in preganglionic and postganglionic adrenergic neurons, the latter through activation of α-1 adrenoreceptors. Previous studies found that patients with neurogenic orthostatic hypotension can improve standing blood pressure and reduce symptoms of neurogenic orthostatic hypotension after a single administration of the selective NRI atomoxetine. This effect was primarily observed in patients with impaired central autonomic pathways with otherwise normal postganglionic sympathetic fibers, known as multiple system atrophy. Likewise, patients with normal or high norepinephrine levels may benefit from NRIs. The long-term efficacy of NRIs for the treatment of neurogenic orthostatic hypotension-related symptoms is currently under investigation. In summary, an in-depth understanding of the pathophysiology of neurogenic orthostatic hypotension resulted in the discovery of a new therapeutic pathway targeted by NRI.
Topics: Humans; Hypotension, Orthostatic; Adrenergic Uptake Inhibitors; Norepinephrine; Atomoxetine Hydrochloride; Norepinephrine Plasma Membrane Transport Proteins; Blood Pressure
PubMed: 38766862
DOI: 10.1161/HYPERTENSIONAHA.124.22069 -
Acta Neurochirurgica May 2024Early mobilization is key in neurologically impaired persons, limiting complications and improving long-term recovery. Self-balanced exoskeletons are used in... (Observational Study)
Observational Study
INTRODUCTION
Early mobilization is key in neurologically impaired persons, limiting complications and improving long-term recovery. Self-balanced exoskeletons are used in rehabilitation departments to help patients stand and walk. We report the first case series of exoskeleton use in acute neurosurgery and intensive care patients, evaluating safety, clinical feasibility and patients' satisfaction.
METHODS
We report a retrospective observational study including individuals hospitalized in the neurosurgical intensive care and neurosurgery departments. We included patients with a medical prescription for an exoskeleton session, and who met no contraindication. Patients benefited from standing sessions using a self-balanced exoskeleton (Atalante, Wandercraft, France). Patients and sessions data were collected. Safety, feasibility and adherence were evaluated.
RESULTS
Seventeen patients were scheduled for 70 standing sessions, of which 27 (39%) were completed. They were typically hospitalized for intracranial hemorrhage (74%) and presented with unilateral motor impairments, able to stand but with very insufficient weight shifting to the hemiplegic limb, requiring support (MRC 36.2 ± 3.70, SPB 2.0 ± 1.3, SPD 0.7 ± 0.5). The average duration of standing sessions was 16 ± 9 min. The only side effect was orthostatic hypotension (18.5%), which resolved with returning to seating position. The most frequent reason for not completing a session was understaffing (75%). All patients were satisfied and expressed a desire to repeat it.
CONCLUSIONS
Physiotherapy using the exoskeleton is safe and feasible in the acute neurosurgery setting, although it requires adaptation from the staff to organize the sessions. An efficacy study is ongoing to evaluate the benefits for the patients.
Topics: Humans; Male; Female; Middle Aged; Exoskeleton Device; Retrospective Studies; Aged; Neurosurgical Procedures; Adult; Early Ambulation; Patient Satisfaction; Feasibility Studies
PubMed: 38763932
DOI: 10.1007/s00701-024-06112-z