The Impact of Valsalva Manoeuvres and Exercise on Intracranial Pressure and Cerebrovascular Dynamics in Idiopathic Intracranial Hypertension.

Idiopathic intracranial hypertension (IIH) is a disease characterised by elevated intracranial pressure (ICP). The impact of straining and exercise on ICP regulation is poorly understood yet clinically relevant to IIH patient care. We sought to investigate the impact of Valsalva manoeuvres (VMs) and exercise on ICP and cerebrovascular haemodynamics in IIH. People with IIH were prospectively enrolled and had an intraparenchymal telemetric ICP sensor inserted. Three participants (age [mean ± standard deviation]: 40.3 ± 13.9 years) underwent continuous real-time ICP monitoring coupled with cerebrovascular haemodynamic assessments during VMs and moderate exercise. Participants had IIH with supine ICP measuring 15.3 ± 8.7 mmHg (20.8 ± 11.8 cm cerebrospinal fluid (CSF)) and sitting ICP measuring -4.2 ± 7.9 mmHg (-5.7 ± 10.7 cmCSF). During phase I of a VM ICP increased by 29.4 ± 13.5 mmHg (40.0 ± 18.4 cmCSF) but returned to baseline within 16 seconds from VM onset. The pattern of ICP changes during the VM phases was associated to that of changes in blood pressure, the middle cerebral artery blood velocity and prefrontal cortex haemodynamics. Exercise led to minimal effects on ICP. In conclusion, VM-induced changes in ICP were coupled to cerebrovascular haemodynamics and showed no sustained impact on ICP. Exercise did not lead to prolonged elevation of ICP. Those with IIH experiencing VMs (for example, during exercise and labour) may be reassured at the brief nature of the changes. Future research must look to corroborate the findings in a larger IIH cohort.

The intensity paradox: A systematic review and meta-analysis of its impact on the cardiorespiratory fitness of older adults.

AIM: The present systematic review and meta-analysis aimed to compare the effect of moderate- versus high-intensity aerobic exercise on cardiorespiratory fitness (CRF) in older adults, taking into account the volume of exercise completed. METHODS: The databases MEDLINE (Ovid), EMBASE (Ovid), and CENTRAL (Cochrane Library) were searched to identify randomized controlled trials (RCTs). Two reviewers extracted data and assessed bias. Comprehensive Meta-Analysis software calculated overall effect size, intensity differences, and performed meta-regression analyses using pre-to-post intervention or change scores of peak oxygen uptake (V̇O2 peak). The review included 23 RCTs with 1332 older adults (intervention group: n = 932; control group: n = 400), divided into moderate-intensity (435 older adults) and high-intensity (476 older adults) groups. RESULTS: Meta-regression analysis showed a moderate, but not significant, relationship between exercise intensity and improvements in V̇O2 peak after accounting for the completed exercise volume (ß = 0.31, 95% CI = [-0.04; 0.67]). Additionally, studies comparing moderate- versus high-intensity revealed a small, but not significant, effect in favor of high-intensity (Hedges' g = 0.20, 95% CI = [-0.02; 0.41]). Finally, no significant differences in V̇O2 peak improvements were found across exercise groups employing various methods, modalities, and intensity monitoring strategies. CONCLUSION: Findings challenge the notion that high-intensity exercise is inherently superior and indicate that regular aerobic exercise, irrespective of the specific approach and intensity, provides the primary benefits to CRF in older adults. Future RCTs should prioritize valid and reliable methodologies for monitoring and reporting exercise volume and adherence among older adults.

Exposure to passive heat and cold stress differentially modulates cerebrovascular-CO2 responsiveness.

Heat and cold stress influence cerebral blood flow (CBF) regulatory factors (e.g., arterial CO2 partial pressure). However, it is unclear whether the CBF response to a CO2 stimulus (i.e., cerebrovascular-CO2 responsiveness) is maintained under different thermal conditions. This study aimed to compare cerebrovascular-CO2 responsiveness between normothermia, passive heat, and cold stress conditions. Sixteen participants (8 females; 25 ± 7 yr) completed two experimental sessions (randomized) comprising normothermic and either passive heat or cold stress conditions. Middle and posterior cerebral artery velocity (MCAv, PCAv) were measured during rest, hypercapnia (5% CO2 inhalation), and hypocapnia (voluntary hyperventilation to an end-tidal CO2 of 30 mmHg). The linear slope of the cerebral blood velocity (CBv) response to changing end-tidal CO2 was calculated to measure cerebrovascular-CO2 responsiveness, and cerebrovascular conductance (CVC) was used to examine responsiveness independent of blood pressure. CBv-CVC-CO2 responsiveness to hypocapnia was greater during heat stress compared with cold stress (MCA: +0.05 ± 0.08 cm/s/mmHg/mmHg, P = 0.04; PCA: +0.02 ± 0.02 cm/s/mmHg/mmHg, P = 0.002). CBv-CO2 responsiveness to hypercapnia decreased during heat stress (MCA: -0.67 ± 0.89 cm/s/mmHg, P = 0.02; PCA: -0.64 ± 0.62 cm/s/mmHg; P = 0.01) and increased during cold stress (MCA: +0.98 ± 1.33 cm/s/mmHg, P = 0.03; PCA: +1.00 ± 0.82 cm/s/mmHg; P = 0.01) compared with normothermia. However, CBv-CVC-CO2 responsiveness to hypercapnia was not different between thermal conditions (P > 0.08). Overall, passive heat, but not cold, stress challenges the maintenance of cerebral perfusion. A greater cerebrovascular responsiveness to hypocapnia during heat stress likely reduces an already impaired cerebrovascular reserve capacity and may contribute to adverse events (e.g., syncope).NEW & NOTEWORTHY This study demonstrates that thermoregulatory-driven perfusion pressure changes, from either cold or heat stress, impact cerebrovascular responsiveness to hypercapnia. Compared with cold stress, heat stress poses a greater challenge to the maintenance of cerebral perfusion during hypocapnia, challenging cerebrovascular reserve capacity while increasing cerebrovascular-CO2 responsiveness. This likely exacerbates cerebral hypoperfusion during heat stress since hyperthermia-induced hyperventilation results in hypocapnia. No regional differences in middle and posterior cerebral artery responsiveness were found with thermal stress.

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. Changes in CBF may have a critical role via effects on central chemo-sensitivity during sleep. METHODS: Polysomnography (PSG) was performed on volunteers after administration of I.V. Acetazolamide (ACZ-10mg/kg) + Dobutamine (DOB-2-5 µg/kg/min) to increase CBF (via Duplex-ultrasound). Central sleep apnea (CSA) was measured from NREM sleep. The duty ratio (DR) was calculated as ventilatory duration (s) divided by cycle duration (s) (hyperpnea/hyperpnea + apnea), LG = 2π/(2πDR-sin2πDR). RESULTS: A total of 11 volunteers were studied. Compared to placebo-control, ACZ/DOB showed a significant increase in the DR (0.79 ± 0.21 vs 0.52 ± 0.03, P = 0.002) and reduction in LG (1.90 ± 0.23 vs 1.29 ± 0.35, P = 0.0004). ACZ/DOB increased cardiac output (CO) (8.19 ± 2.06 vs 6.58 ± 1.56L/min, P = 0.02) and CBF (718 ± 120 vs 526 ± 110ml/min, P < 0.001). There was no significant change in arterial blood gases, minute ventilation (VE), or hypoxic ventilatory response (HVR). However, there was a reduction of hypercapnic ventilatory response (HCVR) by 29% (5.9 ± 2.7 vs 4.2 ± 2.8 L/min, P = 0.1). CONCLUSION: Pharmacological elevation in CBF significantly reduced LG and severity of CSA. We speculate the effect was on HCVR "controller gain," rather than "plant gain," because PaCO2 and VE were unchanged. An effect via reduced circulation time is unlikely, as the respiratory-cycle length did not change.

Exercise and aerobic capacity in individuals with spinal cord injury: A systematic review with meta-analysis and meta-regression.

BACKGROUND: A low level of cardiorespiratory fitness [CRF; defined as peak oxygen uptake ([Formula: see text]O2peak) or peak power output (PPO)] is a widely reported consequence of spinal cord injury (SCI) and a major risk factor associated with chronic disease. However, CRF can be modified by exercise. This systematic review with meta-analysis and meta-regression aimed to assess whether certain SCI characteristics and/or specific exercise considerations are moderators of changes in CRF. METHODS AND FINDINGS: Databases (MEDLINE, EMBASE, CENTRAL, and Web of Science) were searched from inception to March 2023. A primary meta-analysis was conducted including randomised controlled trials (RCTs; exercise interventions lasting >2 weeks relative to control groups). A secondary meta-analysis pooled independent exercise interventions >2 weeks from longitudinal pre-post and RCT studies to explore whether subgroup differences in injury characteristics and/or exercise intervention parameters explained CRF changes. Further analyses included cohort, cross-sectional, and observational study designs. Outcome measures of interest were absolute (A[Formula: see text]O2peak) or relative [Formula: see text]O2peak (R[Formula: see text]O2peak), and/or PPO. Bias/quality was assessed via The Cochrane Risk of Bias 2 and the National Institute of Health Quality Assessment Tools. Certainty of the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Random effects models were used in all meta-analyses and meta-regressions. Of 21,020 identified records, 120 studies comprising 29 RCTs, 67 pre-post studies, 11 cohort, 7 cross-sectional, and 6 observational studies were included. The primary meta-analysis revealed significant improvements in A[Formula: see text]O2peak [0.16 (0.07, 0.25) L/min], R[Formula: see text]O2peak [2.9 (1.8, 3.9) mL/kg/min], and PPO [9 (5, 14) W] with exercise, relative to controls (p < 0.001). Ninety-six studies (117 independent exercise interventions comprising 1,331 adults with SCI) were included in the secondary, pooled meta-analysis which demonstrated significant increases in A[Formula: see text]O2peak [0.22 (0.17, 0.26) L/min], R[Formula: see text]O2peak [2.8 (2.2, 3.3) mL/kg/min], and PPO [11 (9, 13) W] (p < 0.001) following exercise interventions. There were subgroup differences for R[Formula: see text]O2peak based on exercise modality (p = 0.002) and intervention length (p = 0.01), but there were no differences for A[Formula: see text]O2peak. There were subgroup differences (p ≤ 0.018) for PPO based on time since injury, neurological level of injury, exercise modality, and frequency. The meta-regression found that studies with a higher mean age of participants were associated with smaller changes in A[Formula: see text]O2peak and R[Formula: see text]O2peak (p < 0.10). GRADE indicated a moderate level of certainty in the estimated effect for R[Formula: see text]O2peak, but low levels for A[Formula: see text]O2peak and PPO. This review may be limited by the small number of RCTs, which prevented a subgroup analysis within this specific study design. CONCLUSIONS: Our primary meta-analysis confirms that performing exercise >2 weeks results in significant improvements to A[Formula: see text]O2peak, R[Formula: see text]O2peak, and PPO in individuals with SCI. The pooled meta-analysis subgroup comparisons identified that exercise interventions lasting up to 12 weeks yield the greatest change in R[Formula: see text]O2peak. Upper-body aerobic exercise and resistance training also appear the most effective at improving R[Formula: see text]O2peak and PPO. Furthermore, acutely injured, individuals with paraplegia, exercising for ≥3 sessions/week will likely experience the greatest change in PPO. Ageing seemingly diminishes the adaptive CRF responses to exercise training in individuals with SCI. REGISTRATION: PROSPERO: CRD42018104342.

Fat Consumption Attenuates Cortical Oxygenation during Mental Stress in Young Healthy Adults.

Mental stress has been associated with cardiovascular events and stroke, and has also been linked with poorer brain function, likely due to its impact on cerebral vasculature. During periods of stress, individuals often increase their consumption of unhealthy foods, especially high-fat foods. Both high-fat intake and mental stress are known to impair endothelial function, yet few studies have investigated the effects of fat consumption on cerebrovascular outcomes during periods of mental stress. Therefore, this study examined whether a high-fat breakfast prior to a mental stress task would alter cortical oxygenation and carotid blood flow in young healthy adults. In a randomised, counterbalanced, cross-over, postprandial intervention study, 21 healthy males and females ingested a high-fat (56.5 g fat) or a low-fat (11.4 g fat) breakfast 1.5 h before an 8-min mental stress task. Common carotid artery (CCA) diameter and blood flow were assessed at pre-meal baseline, 1 h 15 min post-meal at rest, and 10, 30, and 90 min following stress. Pre-frontal cortex (PFC) tissue oxygenation (near-infrared spectroscopy, NIRS) and cardiovascular activity were assessed post-meal at rest and during stress. Mental stress increased heart rate, systolic and diastolic blood pressure, and PFC tissue oxygenation. Importantly, the high-fat breakfast reduced the stress-induced increase in PFC tissue oxygenation, despite no differences in cardiovascular responses between high- and low-fat meals. Fat and stress had no effect on resting CCA blood flow, whilst CCA diameter increased following consumption of both meals. This is the first study to show that fat consumption may impair PFC perfusion during episodes of stress in young healthy adults. Given the prevalence of consuming high-fat foods during stressful periods, these findings have important implications for future research to explore the relationship between food choices and cerebral haemodynamics during mental stress.

Effects of Stroop task duration on subsequent cognitive and physical performance.

The strength model of self-control purports to explain why brief cognitive response inhibition tasks impair subsequent isometric handgrip endurance. According to the model, ego depleting tasks requiring self-control resources impair performance on subsequent tasks that also require self-control resources. However, several lines of evidence challenge this model, including evidence of improved exercise performance following longer cognitive tasks. Our study investigated the effects of cognitive task duration on (1) subsequent physical endurance performance, (2) concurrent cognitive task performance, and (3) subsequent novel cognitive task performance. Adopting an experimental design, with Stroop task type (incongruent, congruent) and duration (5, 10, 20 min) as between-participant factors, participants (N = 180) completed a color word Stroop task, an isometric handgrip to exhaustion task, and a novel 5-min incongruent number word Stroop task. In the handgrip task, endurance performance was worse following incongruent word Stroop than congruent word Stroop for 10-min tasks but not 5-min and 20-min tasks. In the word Stroop task, accuracy was lower and speed was slower following incongruent word Stroop than congruent word Stroop. Importantly, reaction times improved with longer task durations. In the novel number Stroop task, accuracy was higher following incongruent word Stroop than congruent word Stroop. In conclusion, the finding that the ego depletion effect was moderated by cognitive task duration is better explained by the expected value of control model than the strength model.

Single vesicle analysis reveals the release of tetraspanin positive extracellular vesicles into circulation with high intensity intermittent exercise.

Small extracellular vesicles (sEVs) are released from all cell types and participate in the intercellular exchange of proteins, lipids, metabolites and nucleic acids. Proteomic, flow cytometry and nanoparticle tracking analyses suggest sEVs are released into circulation with exercise. However, interpretation of these data may be influenced by sources of bias introduced by different analytical approaches. Seven healthy participants carried out a high intensity intermittent training (HIIT) cycle protocol consisting of 4 × 30 s at a work-rate corresponding to 200% of individual max power (watts) interspersed by 4.5 min of active recovery. EDTA-treated blood was collected before and immediately after the final effort. Platelet-poor (PPP) and platelet-free (PFP) plasma was derived by one or two centrifugal spins at 2500 g, respectively (15 min, room temperature). Platelets were counted on an automated haemocytometer. Plasma samples were assessed with the Exoview R100 platform, which immobilises sEVs expressing common tetraspanin markers CD9, CD63, CD81 and CD41a on microfluidic chips and with the aid of fluorescence imaging, counts their abundance at a single sEV resolution, importantly, without a pre-isolation step. There was a lower number of platelets in the PFP than PPP, which was associated with a lower number of CD9, CD63 and CD41a positive sEVs. HIIT induced an increase in fluorescence counts in CD9, CD63 and CD81 positive sEVs in both PPP and PFP. These data support the concept that sEVs are released into circulation with exercise. Furthermore, platelet-free plasma is the preferred, representative analyte to study sEV dynamics and phenotype during exercise. KEY POINTS: Small extracellular vesicles (sEV) are nano-sized particles containing protein, metabolites, lipid and RNA that can be transferred from cell to cell. Previous findings implicate that sEVs are released into circulation with exhaustive, aerobic exercise, but since there is no gold standard method to isolate sEVs, these findings may be subject to bias introduced by different approaches. Here, we use a novel method to immobilise and image sEVs, at single-vesicle resolution, to show sEVs are released into circulation with high intensity intermittent exercise. Since platelet depletion of plasma results in a reduction in sEVs, platelet-free plasma is the preferred analyte to examine sEV dynamics and phenotype in the context of exercise.

Detrimental effects of physical inactivity on peripheral and brain vasculature in humans: Insights into mechanisms, long-term health consequences and protective strategies.

The growing prevalence of physical inactivity in the population highlights the urgent need for a more comprehensive understanding of how sedentary behaviour affects health, the mechanisms involved and what strategies are effective in counteracting its negative effects. Physical inactivity is an independent risk factor for different pathologies including atherosclerosis, hypertension and cardiovascular disease. It is known to progressively lead to reduced life expectancy and quality of life, and it is the fourth leading risk factor for mortality worldwide. Recent evidence indicates that uninterrupted prolonged sitting and short-term inactivity periods impair endothelial function (measured by flow-mediated dilation) and induce arterial structural alterations, predominantly in the lower body vasculature. Similar effects may occur in the cerebral vasculature, with recent evidence showing impairments in cerebral blood flow following prolonged sitting. The precise molecular and physiological mechanisms underlying inactivity-induced vascular dysfunction in humans are yet to be fully established, although evidence to date indicates that it may involve modulation of shear stress, inflammatory and vascular biomarkers. Despite the steady increase in sedentarism in our societies, only a few intervention strategies have been investigated for their efficacy in counteracting the associated vascular impairments. The current review provides a comprehensive overview of the evidence linking acute and short-term physical inactivity to detrimental effects on peripheral, central and cerebral vascular health in humans. We further examine the underlying molecular and physiological mechanisms and attempt to link these to long-term consequences for cardiovascular health. Finally, we summarize and discuss the efficacy of lifestyle interventions in offsetting the negative consequences of physical inactivity.

Non-pharmacological interventions for vascular health and the role of the endothelium.

The most common non-pharmacological intervention for both peripheral and cerebral vascular health is regular physical activity (e.g., exercise training), which improves function across a range of exercise intensities and modalities. Numerous non-exercising approaches have also been suggested to improved vascular function, including repeated ischemic preconditioning (IPC); heat therapy such as hot water bathing and sauna; and pneumatic compression. Chronic adaptive responses have been observed across a number of these approaches, yet the precise mechanisms that underlie these effects in humans are not fully understood. Acute increases in blood flow and circulating signalling factors that induce responses in endothelial function are likely to be key moderators driving these adaptations. While the impact on circulating factors and environmental mechanisms for adaptation may vary between approaches, in essence, they all centre around acutely elevating blood flow throughout the circulation and stimulating improved endothelium-dependent vascular function and ultimately vascular health. Here, we review our current understanding of the mechanisms driving endothelial adaptation to repeated exposure to elevated blood flow, and the interplay between this response and changes in circulating factors. In addition, we will consider the limitations in our current knowledge base and how these may be best addressed through the selection of more physiologically relevant experimental models and research. Ultimately, improving our understanding of the unique impact that non-pharmacological interventions have on the vasculature will allow us to develop superior strategies to tackle declining vascular function across the lifespan, prevent avoidable vascular-related disease, and alleviate dependency on drug-based interventions.

Cognitive tasks elicit mental fatigue and impair subsequent physical task endurance: Effects of task duration and type.

Although mentally fatiguing cognitive tasks can impair subsequent physical endurance, the importance of cognitive task duration and the role of response inhibition remain unclear. This study compared the effects of a serial incongruent Stroop color-classification task (i.e., with response inhibition) and N-back memory updating task (i.e., without response inhibition) on mental fatigue and subsequent rhythmic handgrip exercise. Participants (N = 90) were randomly assigned to one of three cognitive task groups (Stroop, 2-back, control) and completed four 10-min blocks of one cognitive task followed by a 5-min physical endurance task (self-paced rhythmic handgrip exercise). Heart rate, heart rate variability, electromyographic forearm activity, and force were recorded throughout along with self-reported measures of fatigue, exertion, and motivation. From the start, the Stroop and 2-back tasks elicited higher heart rate and lower heart rate variability as well as greater fatigue, effort, and interest/enjoyment than the control task. From the second block onwards, the Stroop and 2-back groups produced less force than the control group. There were no group differences in forearm muscle activity. In sum, mental fatigue was induced after performing a cognitive task for 10 mins, whereas muscular endurance was impaired after performing a cognitive task for 20 mins. That these effects were observed for both types of cognitive task indicates that response inhibition is not a necessary condition. The cognitive task duration required to induce mental fatigue and impair rhythmic handgrip endurance performance lay between the durations reported previously for isometric (a few minutes) and whole-body (half an hour) endurance exercise.

Baseline Psychological Traits Contribute to Lake Louise Acute Mountain Sickness Score at High Altitude.

Talks, Benjamin James, Catherine Campbell, Stephanie J. Larcombe, Lucy Marlow, Sarah L. Finnegan, Christopher T. Lewis, Samuel J.E. Lucas, Olivia K. Harrison, and Kyle T.S. Pattinson. Baseline psychological traits contribute to Lake Louise Acute Mountain Sickness score at high altitude. High Alt Med Biol. 23:69-77, 2022. Background: Interoception refers to an individual's ability to sense their internal bodily sensations. Acute mountain sickness (AMS) is a common feature of ascent to high altitude that is only partially explained by measures of peripheral physiology. We hypothesized that interoceptive ability may explain the disconnect between measures of physiology and symptom experience in AMS. Methods: Two groups of 18 participants were recruited to complete a respiratory interoceptive task three times at 2-week intervals. The control group remained in Birmingham (140 m altitude) for all three tests. The altitude group completed test 1 in Birmingham, test 2 the day after arrival at 2,624 m, and test 3 at 2,728 m after an 11-day trek at high altitude (up to 4,800 m). Results: By measuring changes to metacognitive performance, we showed that acute ascent to altitude neither presented an interoceptive challenge, nor acted as interoceptive training. However, AMS symptom burden throughout the trek was found to relate to sea level measures of anxiety, agoraphobia, and neuroticism. Conclusions: This suggests that the Lake Louise AMS score is not solely a reflection of physiological changes on ascent to high altitude, despite often being used as such by researchers and commercial trekking companies alike.

Postexercise urinary alpha-1 acid glycoprotein is not dependent on hypoxia.

Proteinuria is a transient physiological phenomenon that occurs with a range of physical activities and during ascent to altitude. Exercise intensity appears to dictate the magnitude of postexercise proteinuria; however, evidence also indicates the possible contributions from exercise-induced hypoxemia or reoxygenation. Using an environmental hypoxic chamber, this crossover-designed study aimed to evaluate urinary alpha-1 acid glycoprotein (α1-AGP) excretion pre/postexercise performed in hypoxia (HYP) and normoxia (NOR). Sixteen individuals underwent experimental sessions in normoxia (NOR, 20.9% O2) and hypoxia (HYP, 12.0% O2). Sessions began with a 2-h priming period before completing a graded maximal exercise test (GXT) on a cycle ergometer, which was followed by continuation of exposure for an additional 2 h. Physiological responses (i.e., blood pressure, heart rate, and peripheral oxygenation), Lake Louise Scores (LLSs), and urine specimens (analyzed for albumin and α1-AGP) were collected pre- and postexercise (after 30, 60, and 120 min). Peak power output was significantly reduced in HYP (193 ± 45 W) compared with NOR (249 ± 59 W, P < 0.01). Postexercise urinary α1-AGP was greater in NOR (20.04 ± 14.84 µg·min-1) than in HYP (15.08 ± 13.46 µg·min-1), albeit the difference was not significant (P > 0.05). Changes in urinary α1-AGP from pre- to post-30 min were not related to physiological responses or performance outcomes observed during GXT in NOR or HYP. Despite profound systemic hypoxemia with maximal exercise in hypoxia, postexercise α1-AGP excretion was not elevated above the levels observed following normoxic exercise.NEW & NOTEWORTHY By superimposing hypoxic exposure and maximal exercise, we were able to investigate the impact of hypoxia on postexercise proteinuria. Urinalysis for α1-AGP (via particle-enhanced immunoturbidimetry) in specimens collected pre-/postexercise enabled the sensitive detection of altered glomerular permeability. Data indicated that exercise intensity, rather than the degree of exercise-induced hypoxemia, determines postexercise proteinuria.

Menstrual phase influences cerebrovascular responsiveness in females but may not affect sex differences.

Background and aims: Sex differences in the rate and occurrence of cerebrovascular diseases (e.g., stroke) indicate a role for female sex hormones (i.e., oestrogen and progesterone) in cerebrovascular function and regulation. However, it remains unclear how cerebrovascular function differs between the sexes, and between distinct phases of the menstrual cycle. This study aimed to compare cerebrovascular-CO2 responsiveness in 1) females during the early follicular (EF), ovulatory (O) and mid-luteal (ML) phases of their menstrual cycle; and 2) males compared to females during phases of lower oestrogen (EF) and higher oestrogen (O). Methods: Eleven females (25 ± 5 years) complete experimental sessions in the EF (n = 11), O (n = 9) and ML (n = 11) phases of the menstrual cycle. Nine males (22 ± 3 years) completed two experimental sessions, approximately 2 weeks apart for comparison to females. Middle and posterior cerebral artery velocity (MCAv, PCAv) was measured at rest, during two stages of hypercapnia (2% and 5% CO2 inhalation) and hypocapnia (voluntary hyperventilation to an end-tidal CO2 of 30 and 24 mmHg). The linear slope of the cerebral blood velocity response to changes in end-tidal CO2 was calculated to measure cerebrovascular-CO2 responsiveness.. Results: In females, MCAv-CO2 responsiveness to hypocapnia was lower during EF (-.78 ± .45 cm/s/mmHg) when compared to the O phase (-1.17 ± .52 cm/s/mmHg; p < .05) and the ML phase (-1.30 ± .82; p < .05). MCAv-CO2 responsiveness to hypercapnia and hypo-to-hypercapnia, and PCAv-CO2 responsiveness across the CO2 range were similar between menstrual phases (p ≥ .20). MCAv-CO2 responsiveness to hypo-to hypercapnia was greater in females compared to males (3.12 ± .91 cm/s/mmHg vs. 2.31 ± .46 cm/s/mmHg; p = .03), irrespective of menstrual phase (EF or O). Conclusion: Females during O and ML phases have an enhanced vasoconstrictive capacity of the MCA compared to the EF phase. Additionally, biological sex differences can influence cerebrovascular-CO2 responsiveness, dependent on the insonated vessel.

A Systematic Review and Meta-Analysis Examining Whether Changing Ovarian Sex Steroid Hormone Levels Influence Cerebrovascular Function.

Sex differences in cerebrovascular disease rates indicate a possible role for ovarian sex steroid hormones in cerebrovascular function. To synthesise and identify knowledge gaps, a systematic review and meta-analysis was conducted to assess how ovarian sex steroid hormone changes across the lifespan affect cerebrovascular function in women. Three databases (EMBASE, MEDLINE and Web of Science) were systematically searched for studies on adult cerebrovascular function and ovarian sex steroid hormones. Forty-five studies met pre-defined inclusion criteria. Studied hormone groups included hormone replacement therapy (HRT; n = 17), pregnancy (n = 12), menstrual cycle (n = 7), menopause (n = 5), oral contraception (n = 2), and ovarian hyperstimulation (n = 2). Outcome measures included pulsatility index (PI), cerebral blood flow/velocity (CBF), resistance index (RI), cerebral autoregulation, and cerebrovascular reactivity. Meta-analysis was carried out on HRT studies. PI significantly decreased [-0.05, 95% CI: (-0.10, -0.01); p = 0.01] in post-menopausal women undergoing HRT compared to post-menopausal women who were not, though there was considerable heterogeneity (I 2 = 96.8%). No effects of HRT were seen in CBF (p = 0.24) or RI (p = 0.77). This review indicates that HRT improves PI in post-menopausal women. However, there remains insufficient evidence to determine how changing ovarian sex steroid hormone levels affects cerebrovascular function in women during other hormonal phases (e.g., pregnancy, oral contraception).

Sex differences in adaptation to intermittent post-exercise sauna bathing in trained middle-distance runners.

BACKGROUND: The purpose of this study was to investigate the effect of sex on the efficacy of intermittent post-exercise sauna bathing to induce heat acclimation and improve markers of temperate exercise performance in trained athletes. METHODS: Twenty-six trained runners (16 female; mean ± SD, age 19 ± 1 years, V̇O2max F: 52.6 ± 6.9 mL⋅kg-1⋅min-1, M: 64.6 ± 2.4 mL⋅kg-1⋅min-1) performed a running heat tolerance test (30 min, 9 km⋅h-1/2% gradient, 40 °C/40%RH; HTT) and temperate (18 °C) exercise tests (maximal aerobic capacity [V̇O2max] and lactate profile) pre and post 3 weeks of normal exercise training plus 29 ± 1 min post-exercise sauna bathing (101-108 °C) 3 ± 1 times per week. RESULTS: Females and males exhibited similar reductions (interactions p > 0.05) in peak rectal temperature (- 0.3 °C; p < 0.001), skin temperature (- 0.9 °C; p < 0.001) and heart rate (- 9 beats·min-1; p = 0.001) during the HTT at post- vs pre-intervention. Only females exhibited an increase in active sweat glands on the forearm (measured via modified iodine technique; F: + 57%, p < 0.001; M: + 1%, p = 0.47). Conversely, only males increased forearm blood flow (measured via venous occlusion plethysmography; F: + 31%, p = 0.61; M: + 123%; p < 0.001). Females and males showed similar (interactions p > 0.05) improvements in V̇O2max (+ 5%; p = 0.02) and running speed at 4 mmol·L-1 blood lactate concentration (+ 0.4 km·h-1; p = 0.001). CONCLUSIONS: Three weeks of post-exercise sauna bathing effectively induces heat acclimation in females and males, though possibly amid different thermoeffector adaptations. Post-exercise sauna bathing is also an effective ergogenic aid for both sexes.

Losing the dogmatic view of cerebral autoregulation.

In 1959, Niels Lassen illustrated the cerebral autoregulation curve in the classic review article entitled Cerebral Blood Flow and Oxygen Consumption in Man. This concept suggested a relatively broad mean arterial pressure range (~60-150 mmHg) wherein cerebral blood flow remains constant. However, the assumption that this wide cerebral autoregulation plateau could be applied on a within-individual basis is incorrect and greatly variable between individuals. Indeed, each data point on the autoregulatory curve originated from independent samples of participants and patients and represented interindividual relationships between cerebral blood flow and mean arterial pressure. Nonetheless, this influential concept remains commonly cited and illustrated in various high-impact publications and medical textbooks, and is frequently taught in medical and science education without appropriate nuances and caveats. Herein, we provide the rationale and additional experimental data supporting the notion we need to lose this dogmatic view of cerebral autoregulation.

The Acute Cardiorespiratory and Cerebrovascular Response to Resistance Exercise.

Resistance exercise (RE) is a popular modality for the general population and athletes alike, due to the numerous benefits of regular participation. The acute response to dynamic RE is characterised by temporary and bidirectional physiological extremes, not typically seen in continuous aerobic exercise (e.g. cycling) and headlined by phasic perturbations in blood pressure that challenge cerebral blood flow (CBF) regulation. Cerebral autoregulation has been heavily scrutinised over the last decade with new data challenging the effectiveness of this intrinsic flow regulating mechanism, particularly to abrupt changes in blood pressure over the course of seconds (i.e. dynamic cerebral autoregulation), like those observed during RE. Acutely, RE can challenge CBF regulation, resulting in adverse responses (e.g. syncope). Compared with aerobic exercise, RE is relatively understudied, particularly high-intensity dynamic RE with a concurrent Valsalva manoeuvre (VM). However, the VM alone challenges CBF regulation and generates additional complexity when trying to dissociate the mechanisms underpinning the circulatory response to RE. Given the disparate circulatory response between aerobic and RE, primarily the blood pressure profiles, regulation of CBF is ostensibly different. In this review, we summarise current literature and highlight the acute physiological responses to RE, with a focus on the cerebral circulation.

Regulation of cerebral blood flow by arterial PCO2 independent of metabolic acidosis at 5050 m.

KEY POINTS: We investigated the influence of arterial PCO2 (PaCO2 ) with and without experimentally altered pH on cerebral blood flow (CBF) regulation at sea level and with acclimatization to 5050 m. At sea level and high altitude, we assessed stepwise alterations in PaCO2 following metabolic acidosis (via 2 days of oral acetazolamide; ACZ) with and without acute restoration of pH (via intravenous sodium bicarbonate; ACZ+HCO3- ). Total resting CBF was unchanged between trials at each altitude even though arterial pH and [HCO3- ] (i.e. buffering capacity) were effectively altered. The cerebrovascular responses to changes in arterial [H+ ]/pH were consistent with the altered relationship between PaCO2 and [H+ ]/pH following ACZ at high altitude (i.e. leftward x-intercept shifts). Absolute cerebral blood velocity (CBV) and the sensitivity of CBV to PaCO2 was unchanged between trials at high altitude, indicating that CBF is acutely regulated by PaCO2 rather than arterial pH. ABSTRACT: Alterations in acid-base balance with progressive acclimatization to high altitude have been well-established. However, how respiratory alkalosis and the resultant metabolic compensation interact to regulate cerebral blood flow (CBF) is uncertain. We addressed this via three separate experimental trials at sea level and following partial acclimatization (14 to 20 days) at 5050 m; involving: (1) resting acid-base balance (control); (2) following metabolic acidosis via 2 days of oral acetazolamide at 250 mg every 8 h (ACZ; pH: Δ -0.07 ± 0.04 and base excess: Δ -5.7 ± 1.9 mEq⋅l-1 , trial effects: P < 0.001 and P < 0.001, respectively); and (3) after acute normalization of arterial acidosis via intravenous sodium bicarbonate (ACZ + HCO3- ; pH: Δ -0.01 ± 0.04 and base excess: Δ -1.5 ± 2.1 mEq⋅l-1 , trial effects: P = 1.000 and P = 0.052, respectively). Within each trial, we utilized transcranial Doppler ultrasound to assess the cerebral blood velocity (CBV) response to stepwise alterations in arterial PCO2 (PaCO2 ), i.e. cerebrovascular CO2 reactivity. Resting CBF (via Duplex ultrasound) was unaltered between trials within each altitude, indicating that respiratory compensation (i.e. Δ -3.4 ± 2.3 mmHg PaCO2 , trial effect: P < 0.001) was sufficient to offset any elevations in CBF induced via the ACZ-mediated metabolic acidosis. Between trials at high altitude, we observed consistent leftward shifts in both the PaCO2 -pH and CBV-pH responses across the CO2 reactivity tests with experimentally reduced arterial pH via ACZ. When indexed against PaCO2 - rather than pH - the absolute CBV and sensitivity of CBV-PaCO2 was unchanged between trials at high altitude. Taken together, following acclimatization, CO2 -mediated changes in cerebrovascular tone rather than arterial [H+ ]/pH is integral to CBF regulation at high altitude.

Measuring resting cerebral haemodynamics using MRI arterial spin labelling and transcranial Doppler ultrasound: Comparison in younger and older adults.

INTRODUCTION: Resting cerebral blood flow (CBF) and perfusion measures have been used to determine brain health. Studies showing variation in resting CBF with age and fitness level using different imaging approaches have produced mixed findings. We assess the degree to which resting CBF measures through transcranial Doppler (TCD) and arterial spin labeling (ASL) MRI provide complementary information in older and younger, fit and unfit cohorts. METHODS: Thirty-five healthy volunteers (20 younger: 24 ± 7y; 15 older: 66 ± 7y) completed two experimental sessions (TCD/MRI). Aging and fitness effects within and between imaging modalities were assessed. RESULTS: Middle cerebral artery blood velocity (MCAv, TCD) was lower and transit time (MRI) slower in older compared with younger participants (p < .05). The younger group had higher gray matter cerebral perfusion (MRI) than the older group, albeit not significantly (p = .13). Surprisingly, fitness effects in the younger group (decrease/increase in MCAv/transit time with fitness, respectively) opposed the older group (increase/decrease in MCAv/transit time). Whole cohort transit times correlated with MCAv (r=-0.63; p < .05), whereas tissue perfusion did not correlate with TCD measures. CONCLUSION: TCD and MRI modalities provide complementary resting CBF measures, with similar effects across the whole cohort and between subgroups (age/fitness) if metrics are comparable (e.g., velocity [TCD] versus transit time [MRI]).