Confined spaces in space: Cerebral implications of chronic elevations of inspired carbon dioxide and implications for long-duration space travel.

Cerebrovascular regulation is critically dependent upon the arterial partial pressure of carbon dioxide ( ), owing to its effect on cerebral blood flow, tissue , tissue proton concentration, cerebral metabolism and cognitive and neuronal function. In normal environments and in the absence of pathology, at least over acute time frames, hypercapnia is usually managed readily via the respiratory chemoreflex arcs and/or acid-base buffering capacity, such that there is minimal impact on cerebrovascular and neurological function. However, in non-normal environments, such as enclosed spaces, or with pathology, extended exposures to elevations in can be detrimental to cerebral health.

New evidence for baroreflex and respiratory chemoreflex mediated cerebral sympathetic activation in humans.

The brain is highly innervated by sympathetic nerve fibres; however, their physiological purpose is poorly understood. We hypothesized that unilateral cerebral norepinephrine (NE) spillover, an index of cerebral sympathetic nerve activity (SNA), would be elevated when engaging the baroreflex [via lower-body negative pressure (LBNP; -20 and -40 Torr)] and respiratory chemoreflexes [via carbon dioxide (CO) administration (+8 Torr)], independently, and in combination. Twelve young and healthy participants (5 females) underwent simultaneous blood sampling from the right radial artery and internal jugular vein.

Respiratory Dysfunction and Abnormal Hypoxic Ventilatory Response in Mild to Moderate Parkinson's Disease.

Background: Respiratory dysfunction is an important contributor to morbidity and mortality in advanced Parkinson's disease (PD), but it is unclear what parameters are sensitive to diagnose and monitor respiratory dysfunction across disease phases.

Objectives: We aimed to characterize respiratory dysfunction in mild to moderate PD.

Methods: In 20 individuals without cardiopulmonary comorbidity, pulmonary and inspiratory muscle function testing were performed ON-medication.

Micro- and macrovascular function in the highest city in the world: a cross sectional study.

Background: Since vascular responses to hypoxia in both healthy high-altitude natives and chronic mountain sickness (a maladaptive high-altitude pathology characterised by excessive erythrocytosis and the presence of symptoms-CMS) remain unclear, the role of inflammation and oxidative/nitrosative stress on the endothelium- and - responses in both the micro- and macrocirculation, in healthy Andeans at different altitudes and in CMS patients, was examined.

Methods: 94 men were included: 18 lowlanders (LL), 38 healthy highlanders permanently living at 3800 m (n = 21-HL-3800) or in La Rinconada, the highest city in the world (5100-5300 m) (n = 17-HL-5100/No CMS). Moreover, 14 participants with mild (Mild CMS) and 24 with moderate to severe CMS (Mod/Sev CMS) were recruited.

Cardiovascular and hematological responses to a dry dynamic apnea in breath hold divers.

The mammalian dive reflex, characterized by bradycardia and peripheral vasoconstriction, occurs in all mammals, including humans, in response to apnea. However, the dive reflex to a single, maximal, dry, dynamic apnea (DYN) and how it compares to a time-matched exercise control trial (EX) or dry static apnea (SA) has not been studied. We examined the hypotheses that, compared with EX and SA, the magnitude of the ) cardiovascular response and ) hematological response to DYN would be greater.

Evidence for direct CO -mediated alterations in cerebral oxidative metabolism in humans.

Aim: How the cerebral metabolic rates of oxygen and glucose utilization (CMRO and CMR, respectively) are affected by alterations in arterial PCO (PaCO) is equivocal and therefore was the primary question of this study.

Methods: This retrospective analysis involved pooled data from four separate studies, involving 41 healthy adults (35 males/6 females). Participants completed stepwise steady-state alterations in PaCO ranging between 30 and 60 mmHg.

Randomized controlled trial of intermittent hypoxia in Parkinson's disease: study rationale and protocol.

Background: Parkinson's disease (PD) is a neurodegenerative disease for which no disease-modifying therapies exist. Preclinical and clinical evidence suggest that repeated exposure to intermittent hypoxia might have short- and long-term benefits in PD. In a previous exploratory phase I trial, we demonstrated that in-clinic intermittent hypoxia exposure is safe and feasible with short-term symptomatic effects on PD symptoms.

Selected and shared hematological responses to apnea in elite human free divers and northern elephant seals ().

Despite elite human free divers achieving incredible feats in competitive free diving, there has yet to be a study that compares consummate divers, (i.e. northern elephant seals) to highly conditioned free divers (i.

Acute isometric and dynamic exercise do not alter cerebral sympathetic nerve activity in healthy humans.

The impact of physiological stressors on cerebral sympathetic nervous activity (SNA) remains controversial. We hypothesized that cerebral noradrenaline (NA) spillover, an index of cerebral SNA, would not change during both submaximal isometric handgrip (HG) exercise followed by a post-exercise circulatory occlusion (PECO), and supine dynamic cycling exercise. Twelve healthy participants (5 females) underwent simultaneous blood sampling from the right radial artery and right internal jugular vein.

A narrative review of periodic breathing during sleep at high altitude: From acclimatizing lowlanders to adapted highlanders.

Periodic breathing during sleep at high altitude is almost universal among sojourners. Here, in the context of acclimatization and adaptation, we provide a contemporary review on periodic breathing at high altitude, and explore whether this is an adaptive or maladaptive process. The mechanism(s), prevalence and role of periodic breathing in acclimatized lowlanders at high altitude are contrasted with the available data from adapted indigenous populations (e.

Hemorheological, cardiorespiratory, and cerebrovascular effects of pentoxifylline following acclimatization to 3,800 m.

Pentoxifylline is a nonselective phosphodiesterase inhibitor used for the treatment of peripheral artery disease. Pentoxifylline acts through cyclic adenosine monophosphate, thereby enhancing red blood cell deformability, causing vasodilation and decreasing inflammation, and potentially stimulating ventilation. We conducted a double-blind, placebo-controlled, crossover, counter-balanced study to test the hypothesis that pentoxifylline could lower blood viscosity, enhance cerebral blood flow, and decrease pulmonary artery pressure in lowlanders following 11-14 days at 3,800 m.

Intense exercise at high altitude causes platelet loss across the brain in humans.

Platelets are known primarily for their role in blood clotting; however, it is becoming clear that they play diverse roles beyond that of haemostasis. Exercise has been shown to activate platelets and stimulate neurogenesis, neuroplasticity and improve cognitive function, highlighting a potentially powerful link between platelet function and brain health. Despite this clear link between platelets and the brain, very little is known about the behaviour of platelets through the cerebral circulation in humans.

The influence of maturation and sex on intracranial blood velocities during exercise in children.

Cerebral blood velocity (CBv) increases in response to moderate exercise in humans, but the magnitude of change is smaller in children compared with postpubertal adolescents and adults. Whether sex differences exist in the anterior or posterior CBv response to exercise across pubertal development remains to be determined. We assessed middle cerebral artery (MCAv) and posterior cerebral artery (PCAv) blood velocity via transcranial Doppler in 38 prepubertal (18 males) and 48 postpubertal (23 males) with cerebrovascular and cardiorespiratory measures compared at baseline and ventilatory threshold.

Loop gain response to increased cerebral blood flow at high altitude.

Purpose: To compare loop gain (LG) before and during pharmacological increases in cerebral blood flow (CBF) at high altitude (HA). Loop gain (LG) describes stability of a negative-feedback control system; defining the magnitude of response to a disturbance, such as hyperpnea to an apnea in periodic breathing (PB). "Controller-gain" sensitivity from afferent peripheral (PCR) and central-chemoreceptors (CCR) plays a key role in perpetuating PB.

Cerebral uptake of microvesicles occurs in normocapnic but not hypocapnic passive hyperthermia in young healthy male adults.

Passive hyperthermia causes cerebral hypoperfusion primarily from heat-induced respiratory alkalosis. However, despite the cerebral hypoperfusion, it is possible that the mild alkalosis might help to attenuate cerebral inflammation. In this study, the cerebral exchange of extracellular vesicles (microvesicles), which are known to elicit pro-inflammatory responses when released in conditions of stress, were examined in hyperthermia with and without respiratory alkalosis.

Cerebral blood flow and cerebrovascular reactivity are modified by maturational stage and exercise training status during youth.

New Findings: What is the central question of this study? Gonadal hormones modulate cerebrovascular function while insulin-like growth factor 1 (IGF-1) facilitates exercise-mediated cerebral angiogenesis; puberty is a critical period of neurodevelopment alongside elevated gonadal hormone and IGF-1 activity: but whether exercise training across puberty enhances cerebrovascular function is unkown. What is the main finding and its importance? Cerebral blood flow is elevated in endurance trained adolescent males when compared to untrained counterparts. However, cerebrovascular reactivity to hypercapnia is faster in trained vs.

Exercise breaks prevent attenuation in cerebrovascular function following an acute bout of uninterrupted sitting in healthy children.

The purpose of this study was to examine the effect of an acute bout of prolonged sitting with and without exercise breaks on cerebrovascular function in 7- to 13-year-old children. Forty-two children and adolescents were recruited to a crossover trial, with 15 girls (mean age 10.1 ± 2.

Greater male variability in daily energy expenditure develops through puberty.

There is considerably greater variation in metabolic rates between men than between women, in terms of basal, activity and total (daily) energy expenditure (EE). One possible explanation is that EE is associated with male sexual characteristics (which are known to vary more than other traits) such as musculature and athletic capacity. Such traits might be predicted to be most prominent during periods of adolescence and young adulthood, when sexual behaviour develops and peaks.

Impact of Water- and Land-Based Exercise Training on Risk Factors and Vascular Function in Middle-Aged and Older Men and Women.

Introduction: Exercise improves vascular function, but it is unclear whether benefits are mediated by traditional cardiovascular risk factors or whether sex differences in training effects exist in older adults. We hypothesized that exercise would improve cardiovascular risk factors, that males and females would benefit similarly, and that improvements in risk factors would correlate with changes in vascular function.

Methods: Seventy-two healthy middle-aged/older adults (age, 62 ± 7 yr; 26%♂) were randomized to a land-walking ( n = 23), water-walking ( n = 25), or a nonexercise control group (C; n = 23).

Recent insights into mechanisms of hypoxia-induced vasodilatation in the human brain.

The cerebral vasculature manages oxygen delivery by adjusting arterial blood in-flow in the face of reductions in oxygen availability. Hypoxic cerebral vasodilatation, and the associated hypoxic cerebral blood flow reactivity, involve many vascular, erythrocytic and cerebral tissue mechanisms that mediate elevations in cerebral blood flow via micro- and macrovascular dilatation. This contemporary review focuses on in vivo human work - with reference to seminal preclinical work where necessary - on hypoxic cerebrovascular reactivity, particularly where recent advancements have been made.

The jugular venous-to-arterial difference during rebreathing and end-tidal forcing: Relationship with cerebral perfusion.

We examined two assumptions of the modified rebreathing technique for the assessment of the ventilatory central chemoreflex (CCR) and cerebrovascular CO reactivity (CVR), hypothesizing: (1) that rebreathing abolishes the gradient between the partial pressures of arterial and brain tissue CO [measured via the surrogate jugular venous and arterial difference (P CO )] and (2) rebreathing eliminates the capacity of CVR to influence the P CO difference, and thus affect CCR sensitivity. We also evaluated these variables during two separate dynamic end-tidal forcing (ETF) protocols (termed: ETF-1 and ETF-2), another method of assessing CCR sensitivity and CVR. Healthy participants were included in the rebreathing (n = 9), ETF-1 (n = 11) and ETF-2 (n = 10) protocols and underwent radial artery and internal jugular vein (advanced to jugular bulb) catheterization to collect blood samples.