Acute Gravitational Stress Selectively Impairs Dynamic Cerebrovascular Reactivity in the Anterior Circulation Independent of Changes to the Central Respiratory Chemoreflex

Cerebrovascular reactivity (CVR) to changes in the partial pressure of arterial carbon dioxide (PaCO2) is an important mechanism that maintains CO2 or pH homeostasis in the brain. To what extent this is influenced by gravitational stress and corresponding implications for the regulation of cerebral blood flow (CBF) remain unclear. The present study examined the onset responses of pulmonary ventilation (V̇E) and anterior middle (MCA) and posterior (PCA) cerebral artery mean blood velocity (Vmean) responses to acute hypercapnia (5% CO2) to infer dynamic changes in the central respiratory chemoreflex and cerebrovascular reactivity (CVR), in supine and 50° head-up tilt (HUT) positions. Each onset response was evaluated using a single-exponential regression model consisting of the response time latency [CO2-response delay (t0)] and time constant (τ). Onset response of V̇E and PCA Vmean to changes in CO2 was unchanged during 50° HUT compared with supine (τ: V̇E, p = 0.707; PCA Vmean, p = 0.071 vs. supine) but the MCA Vmean onset response was faster during supine than during 50° HUT (τ: p = 0.003 vs. supine). These data indicate that gravitational stress selectively impaired dynamic CVR in the anterior cerebral circulation, whereas the posterior circulation was preserved, independent of any changes to the central respiratory chemoreflex. Collectively, our findings highlight the regional heterogeneity underlying CBF regulation that may have translational implications for the microgravity (and hypercapnia) associated with deep-space flight notwithstanding terrestrial orthostatic diseases that have been linked to accelerated cognitive decline and neurodegeneration.

Potential use of dimensionhydrinate/cinnarizine combination in the treatment of vertigo

Vertigo is a fairly common complaint with which patients present to physicians of various profiles, and especially to general practitioners, neurologists, and otorhinolaryngologists. Vertigo is a condition where a person has the illusion of movement or of surrounding objects moving when they are not. Vertigo is a symptom of a wide range of diseases, both benign and life-threatening. Vertigo can have a variety of causes, and the suggested treatment should depend on the cause. Due to the multifactorial etiology of medical care, many patients receive inadequate treatment under the primary healthcare scheme, especially during initial presentation. The main causes of vertigo are benign paroxysmal positional vertigo, Meniere’s disease, vestibular neuritis, vestibular migraine, and cerebrovascular diseases. Patients with other disorders, such as depression and hyperventilation syndrome, may present with complaints of nonrotary vertigo. Differential diagnosis of vertigo can be made using easy-to-perform tests during physical examination, including assessment of nystagmus, Dix-Hallpike maneuver, and blood pressure measurements with head-up tilt table tests. Treatment of patients with complaints of vertigo includes drug and non-drug therapy, depending on the established nosological form. However, due to the multifactorial etiology, many patients receive inadequate treatment under the primary healthcare scheme, especially during initial presentation. The dimensionhydrinate/cinnarizine combination is one of the drugs for the symptomatic treatment of vertigo of various origins in adults.

Orthostatic Symptoms and Reductions in Cerebral Blood Flow in Long-Haul COVID-19 Patients: Similarities with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Background and Objectives: Symptoms and hemodynamic findings during orthostatic stress have been reported in both long-haul COVID-19 and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), but little work has directly compared patients from these two groups. To investigate the overlap in these clinical phenotypes, we compared orthostatic symptoms in daily life and during head-up tilt, heart rate and blood pressure responses to tilt, and reductions in cerebral blood flow in response to orthostatic stress in long-haul COVID-19 patients, ME/CFS controls, and healthy controls. Materials and Methods: We compared 10 consecutive long-haul COVID-19 cases with 20 age- and gender-matched ME/CFS controls with postural tachycardia syndrome (POTS) during head-up tilt, 20 age- and gender-matched ME/CFS controls with a normal heart rate and blood pressure response to head-up tilt, and 10 age- and gender-matched healthy controls. Identical symptom questionnaires and tilt test procedures were used for all groups, including measurement of cerebral blood flow and cardiac index during the orthostatic stress. Results: There were no significant differences in ME/CFS symptom prevalence between the long-haul COVID-19 patients and the ME/CFS patients. All long-haul COVID-19 patients developed POTS during tilt. Cerebral blood flow and cardiac index were more significantly reduced in the three patient groups compared with the healthy controls. Cardiac index reduction was not different between the three patient groups. The cerebral blood flow reduction was larger in the long-haul COVID-19 patients compared with the ME/CFS patients with a normal heart rate and blood pressure response. Conclusions: The symptoms of long-haul COVID-19 are similar to those of ME/CFS patients, as is the response to tilt testing. Cerebral blood flow and cardiac index reductions during tilt were more severely impaired than in many patients with ME/CFS. The finding of early-onset orthostatic intolerance symptoms, and the high pre-illness physical activity level of the long-haul COVID-19 patients, makes it unlikely that POTS in this group is due to deconditioning. These data suggest that similar to SARS-CoV-1, SARS-CoV-2 infection acts as a trigger for the development of ME/CFS.

Orthostatic intolerance in adults with long COVID was not associated with postural orthostatic tachycardia syndrome

In this observational cross-sectional study, we investigated predictors of orthostatic intolerance (OI) in adults with long COVID. Participants underwent a 3-minute active stand (AS) with Finapres NOVA, followed by a 10-minute unmedicated 70-degree head-up tilt test. 85 participants were included (mean age 46 years, range 25-78; 74% women), of which 56 (66%) reported OI during AS (OIAS). OIAS seemed associated with female sex, more fatigue and depressive symptoms, and greater inability to perform activities of daily living (ADL), as well as a higher heart rate (HR) at the lowest systolic blood pressure (SBP) point before the 1st minute post-stand (mean HRnadir: 88 vs 75 bpm, P=0.004). In a regression model also including age, sex, fatigue, depression, ADL inability, and peak HR after the nadir SBP, HRnadir was the only OIAS predictor (OR=1.09, 95% CI: 1.01-1.18, P=0.027). 22 participants had initial (iOH) and 5 classical (cOH) orthostatic hypotension, but neither correlated with OIAS. 71 participants proceeded to tilt, of which 28 had OI during tilt (OItilt). Of the 53 who had a 10-minute tilt, 7 (13%) fulfilled hemodynamic postural orthostatic tachycardia syndrome (POTS) criteria, but 6 did not report OItilt. OIAS was associated with a higher initial HR on AS, which after 1 minute equalized with the non-OIAS group. Despite these initial orthostatic HR differences, POTS was infrequent and largely asymptomatic. ClinicalTrials.gov Identifier: NCT05027724 (retrospectively registered on August 30, 2021).

Gravitational effects on ocular pressure and perfusion pressure

Changes in the gravitational vector by postural changes or weightlessness induce fluid shifts impacting ocular hemodynamics and regional pressures. This investigation explores the impact of changes in direction of the gravitational vector on intraocular pressure (IOP), mean arterial pressure at eyelevel (MAPeye), and ocular perfusion pressure (OPP), which is critical for ocular health. Thirteen subjects underwent 360° of tilt (including both prone and supine positions) at 15º increments. At each angle, steady-state IOP and MAPeye were measured and OPP calculated as MAPeye-IOP. Experimental data were compared to a 6-compartment lumped parameter model of the eye. Mean IOP, MAPeye, and OPP significantly increased from 0º supine to 90º head down tilt (HDT) by 20.7±1.7 mmHg (ᵅD; < 0.001), 38.5±4.1 mmHg (ᵅD; < 0.001), and 17.4±3.2 mmHg (ᵅD; <0.001), respectively. Head up tilt (HUT) significantly decreased OPP by 16.5±2.5 mmHg (ᵅD; < 0.001). IOP was significantly higher in prone vs. supine position for much of the tilt range. Our study indicates that OPP is highly gravitationally dependent. Specifically, data show that MAPeye is more gravitationally dependent than IOP, thus causing OPP to increase during HDT and to decrease during HUT. Additionally, IOP was elevated in prone position compared to supine position due to the additional hydrostatic column between the base of the rostral globe to the mid-caudal plane, supporting the notion that hydrostatic forces play an important role in ocular hemodynamics. Changes in OPP as a function of changes in gravitational stress and/or weightlessness may play a role in the pathogenesis of spaceflight-associated neuro-ocular syndrome.

Information decomposition in the frequency domain: a new framework to study cardiovascular and cardiorespiratory oscillations

While cross-spectral and information-theoretic approaches are widely used for the multivariate analysis of physiological time series, their combined utilization is far less developed in the literature. This study introduces a framework for the spectral decomposition of multivariate information measures, which provides frequency-specific quantifications of the information shared between a target and two source time series and of its expansion into amounts related to how the sources contribute to the target dynamics with unique, redundant and synergistic information. The framework is illustrated in simulations of linearly interacting stochastic processes, showing how it allows us to retrieve amounts of information shared by the processes within specific frequency bands which are otherwise not detectable by time-domain information measures, as well as coupling features which are not detectable by spectral measures. Then, it is applied to the time series of heart period, systolic and diastolic arterial pressure and respiration variability measured in healthy subjects monitored in the resting supine position and during head-up tilt. We show that the spectral measures of unique, redundant and synergistic information shared by these variability series, integrated within specific frequency bands of physiological interest and reflect the mechanisms of short-term regulation of cardiovascular and cardiorespiratory oscillations and their alterations induced by the postural stress. This article is part of the theme issue 'Advanced computation in cardiovascular physiology: new challenges and opportunities'.