Lower Body Negative Pressure: Physiological Effects, Applications, and Implementation.

This review presents lower body negative pressure (LBNP) as a unique tool to investigate the physiology of integrated systemic compensatory responses to altered hemodynamic patterns during conditions of central hypovolemia in humans. An early review published in Physiological Reviews over 40 yr ago (Wolthuis et al. Physiol Rev 54: 566-595, 1974) focused on the use of LBNP as a tool to study effects of central hypovolemia, while more than a decade ago a review appeared that focused on LBNP as a model of hemorrhagic shock (Cooke et al. J Appl Physiol (1985) 96: 1249-1261, 2004). Since then there has been a great deal of new research that has applied LBNP to investigate complex physiological responses to a variety of challenges including orthostasis, hemorrhage, and other important stressors seen in humans such as microgravity encountered during spaceflight. The LBNP stimulus has provided novel insights into the physiology underlying areas such as intolerance to reduced central blood volume, sex differences concerning blood pressure regulation, autonomic dysfunctions, adaptations to exercise training, and effects of space flight. Furthermore, approaching cardiovascular assessment using prediction models for orthostatic capacity in healthy populations, derived from LBNP tolerance protocols, has provided important insights into the mechanisms of orthostatic hypotension and central hypovolemia, especially in some patient populations as well as in healthy subjects. This review also presents a concise discussion of mathematical modeling regarding compensatory responses induced by LBNP. Given the diverse applications of LBNP, it is to be expected that new and innovative applications of LBNP will be developed to explore the complex physiological mechanisms that underline health and disease.

Implanted System for Orthostatic Hypotension in Multiple-System Atrophy.

Orthostatic hypotension is a cardinal feature of multiple-system atrophy. The upright posture provokes syncopal episodes that prevent patients from standing and walking for more than brief periods. We implanted a system to restore regulation of blood pressure and enable a patient with multiple-system atrophy to stand and walk after having lost these abilities because of orthostatic hypotension. This system involved epidural electrical stimulation delivered over the thoracic spinal cord with accelerometers that detected changes in body position. (Funded by the Defitech Foundation.).

In hypertension, with or without orthostatic hypotension, more- vs. less-intensive BP therapy improves clinical outcomes.

SOURCE CITATION: Juraschek SP, Hu JR, Cluett JL, et al. Orthostatic hypotension, hypertension treatment, and cardiovascular disease: an individual participant meta-analysis. JAMA. 2023;330:1459-1471. 37847274.

A novel mechanism of idiopathic orthostatic hypotension and hypocatecholaminemia due to autoimmunity against aromatic l-Amino acid decarboxylase.

Orthostatic hypotension (OH) is a common condition. Many potential etiologies of OH have been identified, but in clinical practice the underlying cause of OH is often unknown. In the present study, we identified a novel and extraordinary etiology of OH. We describe a first case of acquired severe OH with syncope, and the female patient had extremely low levels of catecholamines and serotonin in plasma, urine and cerebrospinal fluid (CSF). Her clinical and biochemical evidence showed a deficiency of the enzyme aromatic l-amino acid decarboxylase (AADC), which converts l-DOPA to dopamine, and 5-hydroxytryptophan to serotonin, respectively. The consequence of pharmacologic stimulation of catecholaminergic nerves and radionuclide examination revealed her catecholaminergic nerves denervation. Moreover, we found that the patient's serum showed presence of autoantibodies against AADC, and that isolated peripheral blood mononuclear cells (PBMCs) from the patient showed cytokine-induced toxicity against AADC. These observations suggest that her autoimmunity against AADC is highly likely to cause toxicity to adrenal medulla and catecholaminergic nerves which contain AADC, resulting in hypocatecholaminemia and severe OH. Administration of vitamin B6, an essential cofactor of AADC, enhanced her residual AADC activity and drastically improved her symptoms. Our data thus provide a new insight into pathogenesis and pathophysiology of OH.

Orthostatic blood pressure changes do not influence cognitive outcomes following intensive blood pressure control.

BACKGROUND: Effects of intensive blood pressure (BP) control on cognitive outcomes in patients with excess orthostatic BP changes are unclear. We aimed to evaluate whether orthostatic BP changes modified the effects of BP intervention on cognitive impairment. METHODS: We analyzed 8547 participants from the Systolic Blood Pressure Intervention Trial Memory and cognition IN Decreased Hypertension. Associations between orthostatic BP changes and incident cognitive outcomes were evaluated by restricted cubic spline curves based on Cox models. The interactions between orthostatic BP changes and intensive BP intervention were assessed. RESULTS: The U-shaped associations were observed between baseline orthostatic systolic BP changes and cognitive outcomes. However, there were insignificant interactions between either change in orthostatic systolic BP (P for interaction = 0.81) or diastolic BP (P for interaction = 0.32) and intensive BP intervention for the composite outcome of probable dementia or mild cognitive impairment (MCI). The hazard ratio of intensive versus standard target for the composite cognitive outcome was 0.82 (95% CI 0.50-1.35) in those with an orthostatic systolic BP reduction of >20 mmHg and 0.41 (95% CI 0.21-0.80) in those with an orthostatic systolic BP increase of >20 mmHg. Results were similar for probable dementia and MCI. The annual changes in global cerebral blood flow (P for interaction = 0.86) consistently favored intensive BP treatment across orthostatic systolic BP changes. CONCLUSION: Intensive BP control did not have a deteriorating effect on cognitive outcomes among hypertensive patients experiencing significant postural BP changes.

In vivo cerebral metabolic and dopaminergic characteristics in multiple system atrophy with orthostatic hypotension.

PURPOSE: Multiple system atrophy (MSA) is a rare neurodegenerative disease, often presented with orthostatic hypotension (OH), which is a disabling symptom but has not been very explored. Here, we investigated MSA patients with OH by using positron emission tomography (PET) with 18F-fluorodeoxyglucose (18F-FDG) and 11C-N-2-carbomethoxy-3-(4-fluorophenyl)-tropane (11C-CFT) for in vivo evaluation of the glucose metabolism and dopaminergic function of the brain. METHODS: Totally, 51 patients with MSA and 20 healthy controls (HC) who underwent 18F-FDG PET/CT were retrospectively enrolled, among which 24 patients also underwent 11C-CFT PET/CT. All patients were divided into MSA-OH(+) and MSA-OH(-) groups. Then, statistical parametric mapping (SPM) method was used to reveal the regional metabolic and dopaminergic characteristics of MSA-OH(+) compared with MSA-OH(-). Moreover, the metabolic networks of MSA-OH(+), MSA-OH(-) and HC groups were also constructed and analyzed based on graph theory to find possible network-level changes in MSA patients with OH. RESULTS: The SPM results showed significant hypometabolism in the pons and right cerebellar tonsil, as well as hypermetabolism in the left parahippocampal gyrus and left superior temporal gyrus in MSA-OH(+) compared with MSA-OH(-). A reduced 11C-CFT uptake in the left caudate was also shown in MSA-OH(+) compared with MSA-OH(-). In the network analysis, significantly reduced local efficiency and clustering coefficient were shown in MSA-OH(+) compared with HC, and decreased nodal centrality in the frontal gyrus was found in MSA-OH(+) compared with MSA-OH(-). CONCLUSION: In this study, the changes in glucose metabolism in the pons, right cerebellar tonsil, left parahippocampal gyrus and left superior temporal gyrus were found closely related to OH in MSA patients. And the decreased presynaptic dopaminergic function in the left caudate may contribute to OH in MSA. Taken together, this study provided in vivo pathophysiologic information on MSA with OH from neuroimaging approach, which is essential for a better understanding of MSA with OH.

Neurogenic orthostatic hypotension in Parkinson's disease: is there a role for locus coeruleus magnetic resonance imaging?

Locus coeruleus (LC) is the main noradrenergic nucleus of the brain, and degenerates early in Parkinson's disease (PD). The objective of this study is to test whether degeneration of the LC is associated with orthostatic hypotension (OH) in PD. A total of 22 cognitively intact PD patients and 52 age-matched healthy volunteers underwent 3 T magnetic resonance (MRI) with neuromelanin-sensitive T1-weighted sequences (LC-MRI). For each subject, a template space-based LC-MRI was used to calculate LC signal intensity (LC contrast ratio-LCCR) and the estimated number of voxels (LCVOX) belonging to LC. Then, we compared the LC-MRI parameters in PD patients with OH (PDOH+) versus without OH (PDOH-) (matched for sex, age, and disease duration) using one-way analysis of variance followed by multiple comparison tests. We also tested for correlations between subject's LC-MRI features and orthostatic drop in systolic blood pressure (SBP). PDOH- and PDOH+ did not differ significantly (p > 0.05) based on demographics and clinical characteristics, except for blood pressure measurements and SCOPA-AUT cardiovascular domain (p < 0.05). LCCR and LCVOX measures were significantly lower in PD compared to HC, while no differences were observed between PDOH- and PDOH+. Additionally, no correlation was found between the LC-MRI parameters and the orthostatic drop in SBP or the clinical severity of autonomic symptoms (p > 0.05). Conversely, RBD symptom severity negatively correlated with several LC-MRI parameters. Our results failed to indicate a link between the LC-MRI features and the presence of OH in PD but confirmed a marked alteration of LC signal in PD patients.

Levodopa-induced orthostatic hypotension in parkinsonism: A red flag of autonomic failure.

BACKGROUND AND PURPOSE: Levodopa (LD) is the main treatment for parkinsonism, but its use may be limited by a potential hypotensive effect. METHODS: We evaluated the cardiovascular effect of LD performing head-up tilt test (HUTT) before and 60 min after 100/25 mg LD/dopa-decarboxylase inhibitor (pre-LD vs. post-LD HUTT) in 164 patients with parkinsonism on chronic LD treatment. Features predictive of LD-induced orthostatic hypotension (OH) were assessed by logistic regression analysis. RESULTS: Basal supine blood pressure (BP) and heart rate (HR) decreased after LD. During post-LD HUTT, BP drop and HR increase were significantly greater than at pre-LD HUTT. Thirty-eight percent of patients had OH at post-LD HUTT compared to 22% of patients presenting OH at pre-LD HUTT (p < 0.001). Risk factors for LD-induced/worsened OH were pre-LD OH (odds ratio [OR] = 36, 95% confidence interval [CI] = 10-131), absence of overshoot at Valsalva maneuver (OR = 9, 95% CI = 4-20), and pathological Valsalva ratio (OR = 6, 95% CI = 2-15). CONCLUSIONS: LD administration caused/worsened hypotension in both supine and orthostatic conditions. Patients with cardiovascular autonomic failure had a higher risk of developing LD-induced OH. In clinical practice, LD-induced OH could represent a red flag for cardiovascular autonomic failure.

Study protocol for the Heads-Up trial: a phase II randomized controlled trial investigating head-up tilt sleeping to alleviate orthostatic intolerance in Parkinson's Disease and parkinsonism.

BACKGROUND: In persons with Parkinson's Disease (PD) or certain forms of atypical parkinsonism, orthostatic hypotension is common and disabling, yet often underrecognized and undertreated. About half of affected individuals also exhibit supine hypertension. This common co-occurrence of both orthostatic hypotension and supine hypertension complicates pharmacological treatments as the treatment of the one can aggravate the other. Whole-body head-up tilt sleeping (HUTS) is the only known intervention that may improve both. Evidence on its effectiveness and tolerability is, however, lacking, and little is known about the implementability. METHODS: In this double-blind multicenter randomized controlled trial (phase II) we will test the efficacy and tolerability of HUTS at different angles in 50 people with PD or parkinsonism who have both symptomatic orthostatic hypotension and supine hypertension. All participants start with one week of horizontal sleeping and subsequently sleep at three different angles, each maintained for two weeks. The exact intervention will vary between the randomly allocated groups. Specifically, the intervention group will consecutively sleep at 6°, 12° and 18°, while the delayed treatment group starts with a placebo angle (1°), followed by 6° and 12°. We will evaluate tolerability using questionnaires and compliance to the study protocol. The primary endpoint is the change in average overnight blood pressure measured by a 24-hour ambulatory blood pressure recording. Secondary outcomes include orthostatic blood pressure, orthostatic tolerance, supine blood pressure, nocturia and various other motor and non-motor tests and questionnaires. DISCUSSION: We hypothesize that HUTS can simultaneously alleviate orthostatic hypotension and supine hypertension, and that higher angles of HUTS are more effective but less tolerable. The Heads-Up trial will help to clarify the effectiveness, tolerability, and feasibility of this intervention at home and can guide at-home implementation. TRIAL REGISTRATION: ClinicalTrials.gov NCT05551377; Date of registration: September 22, 2022.

Mechanism-based therapy of non-cardiac syncope: a practical guide.

The term non-cardiac syncope includes all forms of syncope, in which primary intrinsic cardiac mechanism and non-syncopal transient loss of consciousness can be ruled out. Reflex syncope and orthostatic hypotension are the most frequent aetiologies of non-cardiac syncope. As no specific therapy is effective for all types of non-cardiac syncope, identifying the underlying haemodynamic mechanism is the essential prerequisite for an effective personalized therapy and prevention of syncope recurrences. Indeed, choice of appropriate therapy and its efficacy are largely determined by the syncope mechanism rather than its aetiology and clinical presentation. The two main haemodynamic phenomena leading to non-cardiac syncope include either profound hypotension or extrinsic asystole/pronounced bradycardia, corresponding to two different haemodynamic syncope phenotypes, the hypotensive and bradycardic phenotypes. The choice of therapy-aimed at counteracting hypotension or bradycardia-depends on the given phenotype. Discontinuation of blood pressure-lowering drugs, elastic garments, and blood pressure-elevating agents such as fludrocortisone and midodrine are the most effective therapies in patients with hypotensive phenotype. Cardiac pacing, cardioneuroablation, and drugs preventing bradycardia such as theophylline are the most effective therapies in patients with bradycardic phenotype of extrinsic cause.

Drug-induced orthostatic hypotension: Cluster analysis of co-prescription patterns in older people in UK primary care.

PURPOSE: Over 250 medications are reported to cause orthostatic hypotension, associated with serious adverse outcomes in older adults. Studies suggest a harmful cumulative risk of orthostatic hypotension with multiple medication use. However, there is limited evidence on the potential for harm in practice, particularly which drugs is co-prescribed and may increase risk of orthostatic hypotension. METHODS: Retrospective cohort study and cluster analysis using general practice data from IQVIA Medical Research Data (IMRD) in patients aged ≥50 contributing data between 1 January 2018 and 31 December 2018. Thirteen drug groups known to be associated with orthostatic hypotension by mechanism, were analyzed and clusters generated by sex and age-band. RESULTS: A total of 602 713 individuals aged ≥50 with 283 912 (47%) men and 318 801 (53%) women were included. The most prevalent prescriptions that might contribute to orthostatic hypotension were ACE inhibitors, calcium-channel blockers, beta-blockers, selective serotonin reuptake inhibitors and uroselective alpha-blockers. We identified distinct clusters of cardiovascular system (cardiovascular system) drugs in men and women at all ages. cardiovascular system plus psychoactive drug clusters were common in women at all ages, and in men aged ≤70. cardiovascular system plus uroselective alpha-blockers were identified in men aged ≥70. CONCLUSIONS: Distinct clusters of drugs associated with orthostatic hypotension exist in practice, which change over the life course. Our findings highlight potentially harmful drug combinations that may cause cumulative risk of orthostatic hypotension in older people. This may guide clinicians about the potential of synergistic harm and to monitor for orthostatic hypotension if using combinations of cardiovascular system drugs, cardiovascular system plus psychoactive drugs and/or alpha-blockers-particularly in patients aged ≥70 or at high-risk due to comorbidity. Future research should consider quantifying the risk of drug-induced orthostatic hypotension with such drug combinations.

Syncope in older adults: challenges, approach and treatment.

Syncope can have devastating consequences, resulting in injuries, accidents or even death. In our ageing society, the subsequent healthcare usage, such as emergency room presentations, surgeries and hospital admissions, forms a significant and growing socioeconomic burden. Causes of syncope in the older adult include orthostatic hypotension, carotid sinus syndrome, vasovagal syncope, structural cardiac abnormalities, cardiac arrhythmias and conduction abnormalities. As stated in the recently published World Falls Guidelines, syncope in older adults often presents as falls, which is either due to amnesia for loss of consciousness, or pre-syncope leading to a fall, especially in those prone to falls with several other risk-factors for falls present. This difference in presentation can hinder the recognition of syncope. In patients with unexplained falls, or in whom the history comprises red flags for potential syncope, special attention to (pre)syncope is therefore warranted. When syncope is mistaken for other causes of a transient loss of consciousness, such as epileptic seizures, or when syncope presents as falls, patients are often referred to multiple specialists, which may in turn lead to excessive and unnecessary diagnostic testing and costs. Specialist services that are able to provide a comprehensive assessment can improve diagnostic yield and minimise diagnostic testing, thus improving patient satisfaction. Comprehensive assessment also leads to reduced length of hospital stay. Increasingly, geriatricians are involved in the assessment of syncope in the older patient, especially given the overlap with falls. Therefore, awareness of causes of syncope, as well as state-of-the-art assessment and treatment, is of great importance.

Hypotensive episodes at 24-h ambulatory blood pressure monitoring predict adverse outcomes in Parkinson's disease.

PURPOSE: Neurogenic orthostatic hypotension (nOH) is a frequent nonmotor feature of Parkinson's disease (PD), associated with adverse outcomes. Recently, 24-h ambulatory blood pressure monitoring (ABPM) showed good accuracy in diagnosing nOH. This study aims at evaluating the prognostic role of ABPM-hypotensive episodes in predicting PD disability milestones and mortality and comparing it to the well-defined prognostic role of bedside nOH. METHODS: Patients with PD who underwent ABPM from January 2012 to December 2014 were retrospectively enrolled and assessed for the development of falls, fractures, dementia, bed/wheelchair confinement, hospitalization, and mortality, during an up-to-10-year follow-up. Significant ABPM-hypotensive episodes were identified when greater than or equal to two episodes of systolic BP drop ≥ 15 mmHg (compared with the average 24 h) were recorded during the awakening-to-lunch period. RESULTS: A total of 99 patients (74% male, age 64.0 ± 10.1 years, and PD duration 6.4 ± 4.0 years) were enrolled. At baseline, 38.4% of patients had ABPM-hypotensive episodes and 46.5% had bedside nOH. On Kaplan-Meier analysis, patients with ABPM-hypotensive episodes showed earlier onset of falls (p = 0.001), fractures (p = 0.004), hospitalizations (p = 0.009), bed/wheelchair confinement (p = 0.032), dementia (p = 0.001), and shorter survival (8.0 versus 9.5 years; p = 0.009). At Cox regression analysis (adjusted for age, disease duration, Charlson Comorbidity Index, and Hoehn and Yahr stage) a significant association was confirmed between ABPM-hypotensive episodes and falls [odds ratio (OR) 3.626; p = 0.001), hospitalizations (OR 2.016; p = 0.038), and dementia (OR 2.926; p = 0.008), while bedside nOH was only associated with falls (OR 2.022; p = 0.039) and dementia (OR 1.908; p = 0.048). CONCLUSIONS: The presence of at least two ABPM-hypotensive episodes independently predicted the development of falls, dementia, and hospitalization, showing a stronger prognostic value than the simple bedside assessment.

Tilt-evoked, breathing-driven blood pressure oscillations: Independence from baroreflex-sympathoneural function.

PURPOSE: Orthostasis increases the variability of continuously recorded blood pressure (BP). Low-frequency (LF) BP oscillations (Mayer waves) in this setting are related to the vascular-sympathetic baroreflex. Mechanisms of increased high-frequency (HF) BP oscillations at the periodicity of respiration during orthostasis have received less research attention. A previously reported patient with post-neurosurgical orthostatic hypotension (OH) and vascular-sympathetic baroreflex failure had large tilt-evoked, breathing-driven BP oscillations, suggesting that such oscillations can occur independently of vascular-sympathetic baroreflex modulation. In the present study we assessed effects of orthostasis on BP variability in the frequency domain in patient cohorts with or without OH. METHODS: Power spectral analysis of systolic BP variability was conducted on recordings from 73 research participants, 42 with neurogenic OH [13 pure autonomic failure, 14 Parkinson's disease (PD) with OH, 12 parkinsonian multiple system atrophy, and 3 status post-brainstem neurosurgery] and 31 without OH (control group of 16 healthy volunteers and 15 patients with PD lacking OH), before, during, and after 5' of head-up tilt at 90 degrees from horizontal. The data were log transformed for statistical testing. RESULTS: Across all subjects, head-up tilting increased HF power of systolic BP variability (p = 0.001), without a difference between the neurogenic OH and control groups. LF power during orthostasis was higher in the control than in the OH groups (p = 0.009). CONCLUSIONS: The results of this observational cohort study confirm those based on our case report and lead us to propose that even in the setting of vascular-sympathetic baroreflex failure orthostasis increases HF power of BP variability.

Effect of levodopa on postural blood pressure changes in Parkinson disease: a randomized crossover study.

PURPOSE: We investigated the effect of levodopa on postural blood pressure changes in individuals with Parkinson disease (PD) with (PD+OH) and without neurogenic OH (PD-OH). METHODS: We performed a prospective randomized crossover study with autonomic testing performed ON and OFF levodopa. The primary outcome was the change in systolic blood pressure (SBP) from supine to 70° tilt at 3 min (ΔSBP-3'). Secondary outcomes included indices of baroreflex function and blood pressure and heart rate during tilt. RESULTS: We enrolled 40 individuals with PD (21 PD+OH, 19 PD-OH), mean age (SD) 73.2 years (7.9), 13 women (32.5%)). There was no difference in age, sex, disease duration, and severity between PD+OH and PD-OH. Mean difference in ΔSBP-3' ON versus OFF levodopa in the whole study population was - 3.20 mmHg [- 7.36 to 0.96] (p = 0.14). Mean difference in ΔSBP-3' was - 2.14 mmHg [- 7.55 to 3.28] (p = 0.45) in PD+OH and - 5.14 mmHg [- 11.63 to 1.35] (p = 0.14) in PD-OH. Mean difference in ΔSBP ON versus OFF levodopa was greater at 7 and 10 min (- 7.52 mmHg [- 11.89 to - 3.15], p = 0.002, and - 7.82 mmHg [- 14.02 to - 1.67], p = 0.02 respectively). Levodopa was associated with lower absolute values of blood pressure in both PD+OH and PD-OH and cardiovascular noradrenergic baroreflex impairment. CONCLUSION: Levodopa decreases blood pressure in both PD with and without autonomic failure, but it does not cause a greater fall in blood pressure from supine to standing at 3 min. Levodopa-induced baroreflex sympathetic noradrenergic impairment may contribute to lower blood pressure. Lower standing blood pressure with levodopa may increase the risks of fall and syncope.

Chronic kidney disease and orthostatic hypotension in hospitalised older adults.

PURPOSE: Orthostatic hypotension (OH) may predispose older adults to health complications leading to functional impairment. Despite the central role of the kidney in blood pressure control, the contribution of renal function in orthostatic hypotension is poorly investigated. To verify the association between Chronic Kidney Disease (CKD) and OH a population of hospitalised elderly patients with comorbidities was studied. MATERIALS AND METHODS: 174 patients were consecutively admitted to Acute Geriatric Wards. On admission, patients underwent postural systolic (SBP) and diastolic (DBP) blood pressure evaluation by automatic oscillometric device after 10 min rest in lying position, and in standing position at time 0, 1, 3 and 5 min. CKD was assumed for estimated glomerular filtration rate (e-GFR) less than 60 mL/min/1.73 m2. RESULTS: The mean age of the population enrolled was 74.4 ± 7.0. OH was found in 46.0% and CKD in 56.3% of patients, respectively. A lower e-GFR was observed in patients with (56.1 ± 16.7 mL/min/1.73 m2) than in those without OH (61.1 ± 15.9 mL/min/1.73 m2) (p < 0.05). A greater fall in SBP at 0-min (12.8 ± 6.3 vs. 7.7 ± 3.2 mmHg) and at 1-min (8.4 ± 4.5 vs. 5.7 ± 2.8 mmHg) was found in CKD patients in respect to patients without CKD during active standing test (p < 0.05). Similarly, a DBP reduction at 0-min and at 1-min was observed in CKD patients in respect to patients without CKD (p < 0.05). A multivariate logistic regression analysis showed that CKD was associated to OH (OR 2.426; 95%CI 1.192-4.937; p = 0.014). CONCLUSIONS: CKD is associated to OH in hospitalised older adults.

Orthostatic hypotension: Review and expert position statement.

Orthostatic hypotension is defined as a drop in systolic blood pressure of at least 20mmHg or a drop in diastolic blood pressure of at least 10mmHg within 3minutes of standing. It is a common disorder, especially in high-risk populations such as elderly subjects and patients with neurological diseases, and is associated with markedly increased morbidity and mortality. Its management can be challenging, particularly in cases where supine hypertension is associated with severe orthostatic hypotension. Education of the patient, non-pharmacological measures, and drug adaptation are the cornerstones of treatment. Pharmacological treatment should be individualized according to the severity, underlying cause, 24-hour blood pressure profile, and associated coexisting conditions. First-line therapies are midodrine and fludrocortisone, which may need to be combined for optimal care of severe cases.

[Afferent baroreflex failure with hyponatremia: A case report].

Afferent baroreflex failure (ABF) is a rare disease. It refers to the clinical syndrome caused by the impairment of the afferent limb of the baroreflex or its central connections at the level of the medulla. The recognized causes include trauma, surgery in related areas (radical neck tumor surgery, carotid endarterectomy), neck radiotherapy, brain stem stroke, tumor growth paraganglioma and hereditary diseases, among which the most common cause is extensive neck surgery or radiotherapy for neck cancer. The main manifestations are fluctuating hypertension, orthostatic hypotension, paroxysmal tachycardia and bradycardia. This case is a young man, whose main feature is blood pressure fluctuation, accom-panied by neurogenic orthostatic hypotension (nOH). After examination, the common causes of hypertension and nOH were ruled out. Combined with the previous neck radiotherapy and neck lymph node dissection, it was considered that the blood pressure regulation was abnormal due to the damage of carotid sinus baroreceptor after radiotherapy for nasopharyngeal carcinoma and neck lymph node dissection, which was called ABF. At the same time, the patient was complicated with chronic hyponatremia. Combined with clinical and laboratory examination, the final consideration was caused by syndrome of in- appropriate antidiuretic hormone (SIADH). Baroreceptors controlled the secretion of heart rate, blood pressure and antidiuretic hormone through the mandatory "inhibition" signal. We speculate that the carotid sinus baroreceptor was damaged after neck radiotherapy and surgery, which leads to abnormal blood pressure regulation and nOH, while the function of inhibiting ADH secretion was weakened, resulting in higher ADH than normal level and mild hyponatremia. The goal of treating ABF patients was to reduce the frequency and amplitude of sudden changes in blood pressure and heart rate, and to alleviate the onset of symptomatic hypotension. At present, drug treatment is still controversial, and non-drug treatment may alleviate some patients' symptoms, but long-term effective treatment still needs further study. The incidence of ABF is not high, but it may lead to serious cardiovascular and cerebrovascular events, and the mechanism involved is extremely complicated, and there are few related studies. The reports of relevant medical records warn that patients undergoing neck radiotherapy or surgery should minimize the da-mage to the baroreceptor in the carotid sinus in order to reduce the adverse prognosis caused by complications.

High-intensity exercise does not protect against orthostatic intolerance following bedrest in 55- to 65-yr-old men and women.

Prolonged bedrest provokes orthostatic hypotension and intolerance of upright posture. Limited data are available on the cardiovascular responses of older adults to head-up tilt following bedrest, with no studies examining the potential benefits of exercise to mitigate intolerance in this age group. This randomized controlled trial of head-down bedrest (HDBR) in 55- to 65-yr-old men and women investigated if exercise could avert post-HDBR orthostatic intolerance. Twenty-two healthy older adults (11 female) underwent a strict 14-day HDBR and were assigned to either an exercise (EX) or control (CON) group. The exercise intervention included high-intensity, aerobic, and resistance exercises. Head-up tilt-testing to a maximum of 15 minutes was performed at baseline (Pre-Bedrest) and immediately after HDBR (R1), as well as 6 days (R6) and 4 weeks (R4wk) later. At Pre-Bedrest, three participants did not complete the full 15 minutes of tilt. At R1, 18 did not finish, with no difference in tilt end time between CON (422 ± 287 s) and EX (409 ± 346 s). No differences between CON and EX were observed at R6 or R4wk. At R1, just 1 participant self-terminated the test with symptoms, while 12 others reported symptoms only after physiological test termination criteria were reached. Finishers on R1 protected arterial pressure with higher total peripheral resistance relative to Pre-Bedrest. Cerebral blood velocity decreased linearly with reductions in arterial pressure, end-tidal CO2, and cardiac output. High-intensity interval exercise did not benefit post-HDBR orthostatic tolerance in older adults. Multiple factors were associated with the reduction in cerebral blood velocity leading to intolerance.

The effect of age and mitigation strategies during hot water immersion on orthostatic intolerance and thermal stress.

NEW FINDINGS: What is the central question of this study? The aim was to characterize adverse responses to whole-body hot water immersion and to investigate practical strategies to mitigate these effects. What is the main finding and its importance? Whole-body hot water immersion induced transient orthostatic hypotension and impaired postural control, which recovered to baseline within 10 min. Hot water immersion was well tolerated by middle-aged adults, but younger adults suffered from a greater frequency and severity of dizziness. Cooling the face with a fan or not immersing the arms can mitigate some of these adverse responses in younger adults. ABSTRACT: Hot water immersion improves cardiovascular health and sporting performance, yet its adverse responses are understudied. Thirteen young and 17 middle-aged adults (n = 30) were exposed to 2 × 30 min bouts of whole-body 39°C water immersion. Young adults also completed cooling mitigation strategies in a randomized cross-over design. Orthostatic intolerance and selected physiological, perceptual, postural and cognitive responses were assessed. Orthostatic hypotension occurred in 94% of middle-aged adults and 77% of young adults. Young adults exhibited greater dizziness upon standing (young subjects, 3 out of 10 arbitrary units (AU) vs. middle-aged subjects, 2 out of 10 AU), with four terminating the protocol early owing to dizziness or discomfort. Despite middle-aged adults being largely asymptomatic, both age groups had transient impairments in postural sway after immersion (P < 0.05), but no change in cognitive function (P = 0.58). Middle-aged adults reported lower thermal sensation, higher thermal comfort, and higher basic affect than young adults (all P < 0.01). Cooling mitigation trials had 100% completion rates, with improvements in sit-to-stand dizziness (P < 0.01, arms in, 3 out of 10 AU vs. arms out, 2 out of 10 AU vs. fan, 4 out 10 AU), lower thermal sensation (P = 0.04), higher thermal comfort (P < 0.01) and higher basic affect (P = 0.02). Middle-aged adults were predominantly asymptomatic, and cooling strategies prevented severe dizziness and thermal intolerance in younger adults.