Mechanisms underlying the health benefits of intermittent hypoxia conditioning

The Journal of Physiology, Journal Year: 2023, Volume and Issue: 602(21), P. 5757 - 5783

Published: Oct. 20, 2023

Abstract Intermittent hypoxia (IH) is commonly associated with pathological conditions, particularly obstructive sleep apnoea. However, IH also increasingly used to enhance health and performance emerging as a potent non‐pharmacological intervention against numerous diseases. Whether detrimental or beneficial for largely determined by the intensity, duration, number frequency of hypoxic exposures specific responses they engender. Adaptive protect from future ischaemic insults, improve cellular resilience functions, boost mental physical performance. The systemic mechanisms producing these benefits are highly complex, failure different components can shift long‐term adaptation maladaptation development pathologies. Rather than discussing in detail well‐characterized individual adaptations IH, we here aim summarize integrate hypoxia‐activated into holistic picture body's adaptive specifically demonstrate how might be mobilized their while minimizing risks exposure. image

Language: Английский

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Acid–base balance and cerebrovascular regulation

The Journal of Physiology, Journal Year: 2021, Volume and Issue: 599(24), P. 5337 - 5359

Published: Oct. 27, 2021

The regulation and defence of intracellular pH is essential for homeostasis. Indeed, alterations in cerebrovascular acid-base balance directly affect cerebral blood flow (CBF) which has implications human health disease. For example, changes CBF during disturbances are evident conditions such as chronic obstructive pulmonary disease diabetic ketoacidosis. classic experimental studies from the past 75+ years utilized to describe integrative relationships between CBF, carbon dioxide tension (PCO2 ), bicarbonate (HCO3- ) pH. These factors interact influence (1) time course compensatory respective responses (due rapid exchange kinetics arterial blood, extracellular fluid brain tissue). We propose that [HCO3- ] acute respiratory acidosis/alkalosis contribute regulation; (2) by direct vs. extravascular/interstitial PCO2 - latter recognized proximal compartment alters vascular smooth muscle cell CBF. Taken together, these results substantiate two key ideas: first, affected severity metabolic/respiratory disturbances, including extent partial/full compensation; second, independent diffusion CO2 across blood-brain barrier integral altering perivascular Overall, realizing , HCO3- pH, may provide insights improve clinical practice with treatment systemic disorders.

Language: Английский

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Evidence for direct CO₂‐mediated alterations in cerebral oxidative metabolism in humans

Acta Physiologica, Journal Year: 2024, Volume and Issue: 240(9)

Published: July 3, 2024

How the cerebral metabolic rates of oxygen and glucose utilization (CMRO

Language: Английский

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The Influence of Different Arterial Carbon Dioxide Levels on the Cerebrovascular Autoregulation Curve in a Porcine Cranial Window Model

Neurocritical Care, Journal Year: 2025, Volume and Issue: unknown

Published: April 11, 2025

Language: Английский

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The jugular venous‐to‐arterial PCO2${P_{{\mathrm{C}}{{\mathrm{O}}_{\mathrm{2}}}}}$ difference during rebreathing and end‐tidal forcing: Relationship with cerebral perfusion

The Journal of Physiology, Journal Year: 2023, Volume and Issue: 601(19), P. 4251 - 4262

Published: Aug. 28, 2023

We examined two assumptions of the modified rebreathing technique for assessment ventilatory central chemoreflex (CCR) and cerebrovascular CO2 reactivity (CVR), hypothesizing: (1) that abolishes gradient between partial pressures arterial brain tissue [measured via surrogate jugular venous PCO2${P_{{\mathrm{C}}{{\mathrm{O}}_{\mathrm{2}}}}}$ difference (Pjv-a )] (2) eliminates capacity CVR to influence Pjv-a difference, thus affect CCR sensitivity. also evaluated these variables during separate dynamic end-tidal forcing (ETF) protocols (termed: ETF-1 ETF-2), another method assessing sensitivity CVR. Healthy participants were included in (n = 9), 11) ETF-2 10) underwent radial artery internal vein (advanced bulb) catheterization collect blood samples. Transcranial Doppler ultrasound was used measure middle cerebral velocity (MCAv). The not abolished (6.2 ± 2.6 mmHg; P < 0.001), (9.3 1.5 0.001) or (8.6 1.4 0.001). did change protocol (-0.1 1.2 0.83), but reduced (-3.9 1.1 (-3.4 protocols. Overall, increases MCAv associated with reductions ETF (-0.095 0.089 mmHg cm-1 s-1 ; (-0.028 0.045 · 0.067). These findings suggest that, although is any technique, hyperoxic hypercapnic probably more appropriate assess independent . KEY POINTS: Modified a based on premise Therefore, assumed isolate response stimulation from flow. assessed by measuring bulb compared data against test using forcing. remained present both tests, whereas rebreathing. offer substantiating evidence clarifies refines enhancing interpretation future findings.

Language: Английский

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A test of the interaction between central and peripheral respiratory chemoreflexes in humans

The Journal of Physiology, Journal Year: 2023, Volume and Issue: 601(20), P. 4591 - 4609

Published: Aug. 11, 2023

How central and peripheral chemoreceptor drives to breathe interact in humans remains contentious. We measured the chemoreflex sensitivity hypoxia (PChS) at various isocapnic CO2 tensions ( PCO2${P_{{\mathrm{C}}{{\mathrm{O}}_{\mathrm{2}}}}}$ ) determine form of relationship between PChS . Twenty participants (10F) completed three repetitions modified rebreathing tests with end-tidal PO2${P_{{{\mathrm{O}}_{\mathrm{2}}}}}$ PETO2${P_{{\mathrm{ET}}{{\mathrm{O}}_{\mathrm{2}}}}}$ clamped 150, 70, 60 45 mmHg. End-tidal PETCO2${P_{{\mathrm{ETC}}{{\mathrm{O}}_{\mathrm{2}}}}}$ ), , ventilation V̇$\dot{V}$E calculated oxygen saturation (SC O2 were breath-by-breath by gas-analyser pneumotach. The - repeat-trials linear-interpolated, combined, averaged into 1 mmHg bins, fitted a double-linear function S, L min-1 mmHg-1 ). was computed intervals as follows: difference hypoxic profiles hyperoxic profile (∆ calculated; ∆ values plotted against corresponding SC ; linear regression determined (Lmin-1 %SC O2-1 These processing steps repeated each produce vs. relationship. polynomial functions, Akaike information criterion identified best-fit model. One-way measures analysis variance assessed between-condition differences. S increased (P < 0.0001) isoxic from 3.7 ± 1.5 150 4.4 1.8, 5.0 1.6 6.0 2.2 Lmin-1 mmHg, respectively. Mean fell progressively (99.3 0%, 93.7 0.1%, 90.4 0.1% 80.5 0.1%; P 0.0001). In all individuals, this best described model 75%. Despite increasing activation, linearly indicative an additive central-peripheral response. KEY POINTS: carbon dioxide Participants performed fixed ); (rather than polynomial) 15 20. Most did not exhibit hypo- or hyper-additive effect chemoreceptors on indicating that interaction additive.

Language: Английский

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Central and peripheral chemoreflexes in humans with treated hypertension

The Journal of Physiology, Journal Year: 2023, Volume and Issue: 601(12), P. 2425 - 2445

Published: April 4, 2023

Increased peripheral chemoreflex sensitivity is a pathogenic feature of human hypertension (HTN), while both central and sensitivities are reportedly augmented in animal models HTN. Herein, we tested the hypothesis that combined Fifteen HTN participants (68 ± 5 years; mean SD) 13 normotensives (NT; 65 6 years) performed two modified rebreathing protocols which partial pressure end-tidal carbon dioxide ( PETCO2${P_{{\rm{ETC}}{{\rm{O}}_2}}}$ ) progressively increased oxygen was clamped at either 150 mmHg (isoxic hyperoxia; activation) or 50 hypoxia; activation). Ventilation V̇E${\dot{V}}_{\rm{E}}$ ; pneumotachometer) muscle sympathetic nerve activity (MSNA; microneurography) were recorded, ventilatory vs. slope) (MSNA recruitment thresholds (breakpoint) calculated. Global cerebral blood flow (gCBF; duplex Doppler) measured, association with responses examined. Central greater than NT (2.48 1.33 1.58 0.42 L min-1 mmHg-1 , P = 0.030: 3.32 1.90 1.77 0.62 a.u. 0.034, respectively), not different between groups. had similar thresholds. A lower gCBF associated an earlier threshold for (R2 0.666, < 0.0001) MSNA 0.698, 0.004) during isoxic hyperoxic rebreathing. These findings indicate perhaps suggest targeting may help some forms KEY POINTS: In (HTN) has been identified as feature, HTN, augmented. this study, We observed compared to age-matched normotensive controls, but no difference found sensitivities. During activation, those total flow. results potential contributory role chemoreceptors pathogenesis support possibility therapeutic

Language: Английский

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Differences in cerebrovascular regulation and ventilatory responses during ramp incremental cycling in children, adolescents, and adults

Journal of Applied Physiology, Journal Year: 2021, Volume and Issue: 131(4), P. 1200 - 1210

Published: Aug. 26, 2021

This is the first study to observe similar increases in cerebral blood flow during incremental exercise adolescents and adults. Increases were smaller children compared with adults associated a greater V̇ E /V̇co 2 slope. also provides evidence on progressive development of regulatory role end-tidal CO transition from childhood adulthood.

Language: Английский

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Cerebral O₂ and CO₂ transport in isovolumic haemodilution: Compensation of cerebral delivery of O₂ and maintenance of cerebrovascular reactivity to CO₂

Journal of Cerebral Blood Flow & Metabolism, Journal Year: 2022, Volume and Issue: 43(1), P. 99 - 114

Published: Sept. 21, 2022

This study investigated the influence of acute reductions in arterial O2 content (CaO2) via isovolumic haemodilution on global cerebral blood flow (gCBF) and cerebrovascular CO2 reactivity (CVR) 11 healthy males (age; 28 ± 7 years: body mass index; 23 2 kg/m2). Radial artery internal jugular vein catheters provided measurement pressure gases, quantification metabolism, washout, trans-cerebral nitrite exchange (ozone based chemiluminescence). Prior to following haemodilution, partial (PaCO2) was elevated with dynamic end-tidal forcing while gCBF measured duplex ultrasound. CVR determined as slope response PaCO2. Replacement ∼20% volume an equal 5% human serum albumin (Alburex® 5%) reduced haemoglobin (13.8 0.8 vs. 11.3 0.6 g/dL; P < 0.001) CaO2 (18.9 1.0 vs 15.0 mL/dL 0.001), (+18 11%; = 0.002), preserved oxygen delivery (P 0.49), washout (+11%; 0.01). The net uptake (11.6 14.0 nmol/min; 0.027) at baseline abolished (-3.6 17.9 0.54), perhaps underpinning conservation (61.7 19.0 69.0 19.2 mL/min/mmHg; 0.23). These findings demonstrate that responses anaemia humans are sufficient support maintenance CVR.

Language: Английский

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Transcranial Doppler Ultrasonography detection on cerebrovascular flow for evaluating neonatal hypoxic-ischemic encephalopathy modeling

Frontiers in Neuroscience, Journal Year: 2023, Volume and Issue: 17

Published: May 12, 2023

This study aimed to investigate the feasibility of Transcranial Doppler Ultrasonography (TCD) in evaluating neonatal hypoxic-ischemic encephalopathy (NHIE) modeling through monitoring alteration cerebrovascular flow (HI) rats.

Language: Английский

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