Hypoxic Trials Research Articles

Combined Effects of Hypocapnic Hyperventilation and Hypoxia on Exercise Performance and Metabolic Responses During the Wingate Anaerobic Test.

Hypoxia during supramaximal exercise reduces aerobic metabolism with a compensatory increase in anaerobic metabolism without affecting exercise performance. A similar response is elicited by preexercise voluntary hypocapnic hyperventilation, but it remains unclear whether hypocapnic hyperventilation and hypoxia additively reduce aerobic metabolism and increase anaerobic metabolism during supramaximal exercise. To address that issue, 12 healthy subjects (8 males and 4 females) performed the 30-second Wingate anaerobic test (WAnT) after (1)spontaneous breathing in normoxia (control, ∼21% fraction of inspired O2 [FiO2]), (2)voluntary hypocapnic hyperventilation in normoxia (hypocapnia, ∼21% FiO2), (3)spontaneous breathing in hypoxia (hypoxia, ∼11% FiO2), or (4)voluntary hypocapnic hyperventilation in hypoxia (combined, ∼11% FiO2). Mean power output during the 30-second WAnT was similar among the control (561 [133]W), hypocapnia (563 [140]W), hypoxia (558 [131]W), and combined (560 [133]W) trials (P = .778). Oxygen uptake during the 30-second WAnT was lower in the hypocapnia (1523 [318]mL/min), hypoxia (1567 [300]mL/min), and combined (1203 [318]mL/min) trials than in the control (1935 [250]mL/min) trial, and the uptake in the combined trial was lower than in the hypocapnia or hypoxia trial (all P < .001). Oxygen deficit, an index of anaerobic metabolism, was higher in the hypocapnia (38.4 [7.3]mL/kg), hypoxia (37.8 [6.8]mL/kg), and combined (40.7 [6.9]mL/kg) trials than in the control (35.0 [6.8]mL/kg) trial, and the debt was greater in the combined trial than in the hypocapnia or hypoxia trial (all P < .003). Our results suggest that voluntary hypocapnic hyperventilation and hypoxia additively reduce aerobic metabolism and increase anaerobic metabolism without affecting exercise performance during the 30-second WAnT.

Hypoxia signatures in closed-circuit rebreather divers

Faults or errors during use of closed-circuit rebreathers (CCRs) can cause hypoxia. Military aviators face a similar risk of hypoxia and undergo awareness training to determine their 'hypoxia signature', a personalised, reproducible set of symptoms. We aimed to establish a hypoxia signature among divers, and to investigate their ability to detect hypoxia and self-rescue while cognitively overloaded. Eight CCR divers and 12 scuba divers underwent an initial unblinded hypoxia exposure followed by three trials; a second hypoxic trial and two normoxic trials in randomised order. Hypoxia was induced by breathing on a CCR with no oxygen supply. Subjects pedalled on a cycle ergometer while playing a neurocognitive computer game to simulate real world task loading. Subjects identified hypoxia symptoms by pointing to a board listing common hypoxia symptoms, and were instructed to perform a 'bailout' procedure to mimic self-rescue if they perceived hypoxia. Divers were prompted to bailout if peripheral oxygen saturation fell to 75%, or after six minutes during normoxic trials. Subsequently we interviewed subjects to determine their ability to distinguish hypoxia from normoxia. Ninety-five percent of subjects (19/20) showed agreement between unblinded and blinded hypoxia symptoms. Subjects correctly identified the gas mixture in 85% of the trials. During unblinded hypoxia, only 25% (5/20) of subjects performed unprompted bailout. Fifty-five percent of subjects (11/20) correctly performed the bailout but only when prompted, while 15% (3/20) were unable to bailout despite prompting. During blinded hypoxia 45% of subjects (9/20) performed the bailout unprompted while 15% (3/20) remained unable to bailout despite prompting. Although our data support a normobaric hypoxia signature among both CCR and scuba divers under experimental conditions, most subjects were unable to recognise hypoxia in real time and perform a self-rescue unprompted, although this improved in the second hypoxia trial. These results do not support hypoxia exposure training for CCR divers.

Hypoxia offsets the decline in brachial artery flow-mediated dilation after acute inactivity.

Intermittent (IH), as opposed to continuous hypoxia (CH), is thought to have beneficial effects on cardiovascular function and health. In the present study, we examined the acute effects of IH and CH (∼80% pulse oxygen saturation via 10% oxygen tank) on peripheral vascular function. Brachial artery flow-mediated dilation (FMD) was used to assess vascular function in 12 young adults (23 ± 5 yr; 8 M/4 F) before and after 50 min of IH (5 cycles; 4-min normoxia/6-min hypoxia per cycle), CH (20-min normoxia followed by 30-min hypoxia), or time control (50-min normoxia) interventions. Brachial artery diameter and velocity were measured using Doppler ultrasound to assess blood flow and shear rate. The total change in shear rate was greater during IH (634 ± 1,073·s-1, P < 0.05) and CH (321 ± 833·s-1, P = 0.05) than during time control (-412 ± 789·s-1). %FMD was reduced following time control (7.4 ± 1.2 to 5.9 ± 1.1%, P < 0.05) but was maintained following both hypoxia trials (IH: 7.2 ± 1.5 to 7.5 ± 1.5%, P = 0.52; CH: 6.9 ± 1.6 to 6.8 ± 1.4%, P = 0.73). Normalized %FMD for shear rate area under the curve (%FMDSRAUC) was reduced following the time control trial (4.2 ± 1.4 to 3.7 ± 0.9%, P < 0.05) with no change observed with CH (4.0 ± 1.5 to 3.9 ± 1.4%, P = 0.71). However, %FMDSRAUC increased with IH (3.8 ± 1.1 to 4.5 ± 1.5%, P < 0.05). Our data suggest that acute exposure to hypoxia (both intermittently and continuously) offsets the decline in vascular function after brief inactivity. The potential beneficial effect of hypoxia on peripheral vascular function observed in the current study may be associated with enhanced brachial artery shear in response to the hypoxic challenge.

The Impact of Sprint Interval Exercise in Acute Severe Hypoxia on Executive Function.

Kong, Zhaowei, Qian Yu, Shengyan Sun, On Kei Lei, Yu Tian, Qingde Shi, Jinlei Nie, and Martin Burtscher. The impact of sprint interval exercise in acute severe hypoxia on executive function. High Alt Med Biol. 23: 135-145, 2022. Objective: The present study evaluated executive performance responses to sprint interval exercise in normoxia and relatively severe hypoxia. Methods: Twenty-five physically active men (age 22 ± 2 years; maximal oxygen uptake 43 ± 2 ml/[kg·min]) performed four trials including two normoxic (FIO2 = 0.209) and two normobaric hypoxic trials (FIO2 = 0.112), at rest (control) and exercise at the same time on different days. The exercise scheme consisted of 20 sets of 6-seconds all-out cycling sprint interspersed with 15-seconds recovery. The Stroop task was conducted before, 10, 30, and 60 minutes after each trial, whereas peripheral oxygen saturation (SpO2), heart rate, ratings of perceived exertion, and feelings of arousal were additionally recorded immediately after the interventions. Results: Despite the low SpO2 levels, both resting and sprint interval exercise in hypoxia had no adverse effects on executive function. Exercise elicited executive improvements in normoxia (-5.3% and -3.4% at 10 and 30 minutes after exercise) and in hypoxia (-7.8% and -4.3%), which is reflected by ameliorating incongruent reaction time and its 30-minutes sustained effects (p = 0.018). Conclusions: The findings demonstrate that sprint interval exercise caused sustained executive benefits, and exercise in relatively severe hypoxia did not impair executive performance.

Reproducibility of Respiratory Chemoreflex Characterization by Modified Rebreathing

Modified hypoxic and hyperoxic rebreathing is used to characterize central and peripheral respiratory chemoreflexes in humans. This study examined within‐ and between‐day reproducibility of the key parameters that are identified by this method: ventilatory recruitment threshold (VRT) and chemoreflex sensitivity. Seven healthy males (mean ± SD; age: 27±5 years) visited the laboratory on 4 occasions to performrepetitions of modified rebreathing tests in isoxic‐hypoxic (end‐tidal PO2 (PETO2) =50 mmHg) and ‐hyperoxic conditions (PETO2=150 mmHg). Days 1 and 2 consisted of three repeatedhyperoxic and three hypoxic trials, respectively; Days 3 and 4 included both a hyperoxic and a hypoxic trial completed in a counterbalanced order. Ventilation, end‐tidal PCO2 (PETCO2) and PETO2 were measured breath‐by‐breath by pneumotach and dual gas analyser. For each rebreathing trial, the PETCO2 at which ventilation began to rise was identified as the VRT (mmHg) and the slope of the response above VRT provided respiratory chemoreflex sensitivity (L∙min‐1∙mmHg‐1). Within‐ and between‐day reproducibility was assessed by one‐way ANOVA and intraclass correlation (ICC) analyses. The VRT was not different between trials performed on a single day for bothhyperoxic (44±2, 45±3, vs 44±3 mmHg; for Trials 1, 2, vs 3, respectively; p=0.50; ICC=0.926) and hypoxic rebreathing (40±3, 40±4, vs 40±4 mmHg; p=0.66; ICC=0.994). Chemoreflex sensitivity also was not different between trials performed on the same day in hyperoxic (4.3±2.2, 5.0±3.1, vs4.8±2.3 L∙min‐1∙mmHg‐1; p=0.33; ICC=0.955) or hypoxic conditions (5.6±2.2, 6.2±2.7, 5.7±2.0 L∙min‐1∙mmHg‐1; p=0.33; ICC=0.953). Between days, the VRT was not different for hyperoxic rebreathing (44±3 vs 44±2 vs 45±2 mmHg for Days 1, 3, vs 4, respectively; p=0.10; ICC=0.813) but was different for hypoxic rebreathing (40±3 vs 40±2 vs 41±3 mmHg for Days 2‐4, respectively; p=0.01; ICC=0.931). Chemoreflex sensitivity was not different between days for either hyperoxic (4.8±2.5,4.4±2.7, vs 4.9±2.0 L∙min‐1∙mmHg‐1; p=0.01; ICC=0.906) or hypoxic rebreathing (5.8±2.2, 5.8±2.6, vs 7.8±2.8 L∙min‐1∙mmHg‐1; p=0.01; ICC=0.750). Collectively, these data indicate that model parameters derived from hyperoxic and hypoxic modified rebreathing have good‐to‐excellent test‐retest reproducibility when repeated on the same or different days.

Energy Intake of Men With Excess Weight During Normobaric Hypoxic Confinement.

Due to the observations of weight loss at high altitude, normobaric hypoxia has been considered as a method of weight loss in obese individuals. With this regard, the aim of the present study was to determine the effect of hypoxia per se on metabolism in men with excess weight. Eight men living with excess weight (125.0 ± 17.7 kg; 30.5 ± 11.1 years, BMI: 37.6 ± 6.2 kg⋅m–2) participated in a randomized cross-over study comprising two 10-day confinements: normobaric (altitude of facility ≃ 940 m) normoxia (NORMOXIA; PIO2 = 133 mmHg), and normobaric hypoxia (HYPOXIA). The PIO2 in the latter was reduced from 105 (simulated altitude of 2,800 m) to 98 mmHg (simulated altitude of 3,400 m over 10 days. Before, and at the end of each confinement, participants completed a meal tolerance test (MTT). Resting energy expenditure (REE), circulating glucose, GLP-1, insulin, catecholamines, ghrelin, peptide-YY (PYY), leptin, gastro-intestinal blood flow, and appetite sensations were measured in fasted and postprandial states. Fasting REE increased after HYPOXIA (+358.0 ± 49.3 kcal⋅day–1, p = 0.03), but not after NORMOXIA (−33.1 ± 17.6 kcal⋅day–1). Postprandial REE was also significantly increased after HYPOXIA (p ≤ 0.05), as was the level of PYY. Furthermore, a tendency for decreased energy intake was concomitant with a significant body weight reduction after HYPOXIA (−0.7 ± 0.2 kg) compared to NORMOXIA (+1.0 ± 0.2 kg). The HYPOXIA trial increased the metabolic requirements, with a tendency toward decreased energy intake concomitant with increased PYY levels supporting the notion of a hypoxia-induced appetite inhibition, that could potentially lead to body weight reduction. The greater postprandial blood-glucose response following hypoxic confinement, suggests the potential development of insulin resistance.

Sex differences in the coronary vascular response to combined chemoreflex and metaboreflex stimulation in healthy humans.

What is the central question of this study? Coronary blood flow in healthy humans is controlled by both local metabolic signalling and adrenergic activity: does the integration of these signals during acute hypoxia and adrenergic activation differ between sexes? What are the main findings and its importance? Both males and females exhibit an increase in coronary blood velocity in response to acute hypoxia, a response that is constrained by adrenergic stimulation in males but not females. These findings suggest that coronary blood flow control differs between males and females. Coronary hyperaemia is mediated through multiple signalling pathways, including local metabolic messengers and adrenergic stimulation. This study aimed to determine whether the coronary vascular response to adrenergic stressors is different between sexes in normoxia and hypoxia. Young, healthy participants (n=32; 16F) underwent three randomized trials of isometric handgrip exercise followed by post-exercise circulatory occlusion (PECO) to activate the muscle metaboreflex. End-tidal was controlled at (1) normoxic levels throughout the trial, (2) 50mmHg for the duration of the trial (hypoxia trial), or (3) 50mmHg only during PECO (mixed trial). Mean left anterior descending coronary artery velocity (LADVmean ; transthoracic Doppler echocardiography), heart rate and blood pressure were assessed at baseline and during PECO. In normoxia, there was no change in LADVmean or cardiac workload induced by PECO in males and females. Acute hypoxia increased baseline LADVmean to a greater extent in males compared with females (P<0.05), despite a similar increase in cardiac workload. The change in LADVmean induced by PECO was similar between sexes in normoxia (P=0.31), greater in males during the mixed trial (male: 12.8 (7.7) cm/s vs. female: 8.1 (6.3) cm/s; P=0.02) and reduced in males but not females in acute hypoxia (male: -4.8 (4.5) cm/s vs. female: 0.8 (6.2) cm/s; P=0.006). In summary, sex differences in the coronary vasodilatory response to hypoxia were observed, and metaboreflex activation during hypoxia caused a paradoxical reduction in coronary blood velocity in males but not females.

P005 The effect of alcohol on the motor control of the genioglossus muscle

Abstract Rationale Alcohol is recognised to worsen snoring and obstructive sleep apnea (OSA). This effect is thought to be due to alcohol’s depressant effect on upper airway dilator muscles such as the genioglossus, but how alcohol reduces genioglossus activity is unknown. The aim of this study was to investigate alcohol’s effect on genioglossus single motor units (SMUs). Methods Healthy individuals visited the lab on two days (Alcohol: breath alcohol concentration ~0.08% or Placebo). They were instrumented with a nasal mask, 4 intramuscular genioglossus SMU EMG wires and an ear oximeter. They were exposed to 8–12 hypoxia trials (45-60s of 10%O2 followed by one breath of 100%O2) while awake. The SMUs were sorted according to their firing patterns with respect to respiration and were quantified during baseline, hypoxia, hyperoxia and recovery. Results The total number of SMUs recorded at baseline (68 and 67 respectively) and their distribution (ET: 29 vs 22, IP: 5 vs 10, IT: 8 vs 20 and TT: 26 vs 15 respectively) was similar between conditions. The discharge frequency did not differ between conditions (21Hz vs 22.4Hz, p&amp;gt;0.08). There was no difference between placebo and alcohol in the number (101 vs 88 respectively) and distribution (ET: 35 vs 32, IP: 22 vs 16, IT: 14 vs 22 and TT: 30 vs 17 respectively, p&amp;lt;0.05) of SMUs during hypoxia. Afterdischarge following hypoxia was also not different between conditions. Conclusion Alcohol has little effect on genioglossus SMUs and afterdischarge. OSA following alcohol may be related to increased upper airway resistance/nasal congestion.

Hypoxia Performance Curve: Assess a Whole-Organism Metabolic Shift from a Maximum Aerobic Capacity towards a Glycolytic Capacity in Fish.

The utility of measuring whole-animal performance to frame the metabolic response to environmental hypoxia is well established. Progressively reducing ambient oxygen (O2) will initially limit maximum metabolic rate as a result of a hypoxemic state and ultimately lead to a time-limited, tolerance state supported by substrate-level phosphorylation when the O2 supply can no longer meet basic needs (standard metabolic rate, SMR). The metabolic consequences of declining ambient O2 were conceptually framed for fishes initially by Fry’s hypoxic performance curve, which characterizes the hypoxemic state and its consequences to absolute aerobic scope (AAS), and Hochachka’s concept of scope for hypoxic survival, which characterizes time-limited life when SMR cannot be supported by O2 supply. Yet, despite these two conceptual frameworks, the toolbox to assess whole-animal metabolic performance remains rather limited. Here, we briefly review the ongoing debate concerning the need to standardize the most commonly used assessments of respiratory performance in hypoxic fishes, namely critical O2 (the ambient O2 level below which maintenance metabolism cannot be sustained) and the incipient lethal O2 (the ambient O2 level at which a fish loses the ability to maintain upright equilibrium), and then we advance the idea that the most useful addition to the toolbox will be the limiting-O2 concentration (LOC) performance curve. Using Fry & Hart’s (1948) hypoxia performance curve concept, an LOC curve was subsequently developed as an eco-physiological framework by Neil et al. and derived for a group of fish during a progressive hypoxia trial by Claireaux and Lagardère (1999). In the present review, we show how only minor modifications to available respirometry tools and techniques are needed to generate an LOC curve for individual fish. This individual approach to the LOC curve determination then increases its statistical robustness and importantly opens up the possibility of examining individual variability. Moreover, if peak aerobic performance at a given ambient O2 level of each individual is expressed as a percentage of its AAS, the water dissolved O2 that supports 50% of the individual’s AAS (DOAAS-50) can be interpolated much like the P50 for an O2 hemoglobin dissociation curve (when hemoglobin is 50% saturated with O2). Thus, critical O2, incipient lethal O2, DOAAS-50 and P50 and can be directly compared within and across species. While an LOC curve for individual fish represents a start to an ongoing need to seamlessly integrate aerobic to anaerobic capacity assessments in a single, multiplexed respirometry trial, we close with a comparative exploration of some of the known whole-organism anaerobic and aerobic capacity traits to examine for correlations among them and guide the next steps.

Differential gene expression indicates modulated responses to chronic and intermittent hypoxia in corallivorous fireworms (Hermodice carunculata)

Climate models predict an increase in extent, frequency, and duration of marine hypoxia events in the twenty first century. A better understanding of organismal responses to hypoxia in individual species is a crucial step for predicting ecosystem responses. We experimentally subjected a common invertebrate, the bearded fireworm (Hermodice carunculata) to two levels of chronic hypoxia and, in a separate experiment, to intermittent hypoxia. We found components of the conserved hypoxia-inducible factor (HIF) pathway and show a modulated response to hypoxia depending on the severity of hypoxic stress: under mild hypoxia, only the HIF-1α subunit is upregulated, while expression of the other subunit, aryl hydrocarbon nuclear translator, only increases significantly at more severe hypoxia levels. The chronic trials revealed down-regulation of genes related to cell adhesion, transport, development and heme-binding, and up-regulation of genes related to glycolysis, oxygen binding, cell differentiation, digestive and reproductive function. The intermittent hypoxia trials revealed an upregulation of heme transporter activity during hypoxia, and our time series analysis characterized nine clusters of genes with similar expression patterns. Our findings suggest that H. carunculata is likely to tolerate, and be resilient to, predicted future hypoxia conditions.

Association of noninvasive respiratory support with mortality and intubation rates in acute respiratory failure: a systematic review and network meta-analysis

BackgroundNoninvasive respiratory support devices may reduce the tracheal intubation rate compared with conventional oxygen therapy (COT). To date, few studies have compared high-flow nasal cannula (HFNC) use with noninvasive positive-pressure ventilation (NPPV). We conducted a network meta-analysis to compare the effectiveness of three respiratory support devices in patients with acute respiratory failure.MethodsThe Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, and Ichushi databases were searched. Studies including adults aged ≥ 16 years with acute hypoxic respiratory failure and randomized-controlled trials that compared two different oxygenation devices (COT, NPPV, or HFNC) before tracheal intubation were included. A frequentist-based approach with a multivariate random-effects meta-analysis was used. The network meta-analysis was performed using the GRADE Working Group approach. The outcomes were short-term mortality and intubation rate.ResultsAmong 5507 records, 27 studies (4618 patients) were included. The main cause of acute hypoxic respiratory failure was pneumonia. Compared with COT, NPPV and HFNC use tended to reduce mortality (relative risk, 0.88 and 0.93, respectively; 95% confidence intervals, 0.76–1.01 and 0.80–1.08, respectively; both low certainty) and lower the risk of endotracheal intubation (0.81 and 0.78; 0.72–0.91 and 0.68–0.89, respectively; both low certainty); however, short-term mortality or intubation rates did not differ (0.94 and 1.04, respectively; 0.78–1.15 and 0.88–1.22, respectively; both low certainty) between NPPV and HFNC use.ConclusionNPPV and HFNC use are associated with a decreased risk of endotracheal intubation; however, there are no significant differences in short-term mortality.Trial registrationPROSPERO (registration number: CRD42020139105, 01/21/2020)

Relevance of differential control of sympathorespiratory response magnitudes in clinical assessments.

Relevance of differential control of sympathorespiratory response magnitudes in clinical assessments.

A Novel Method to Measure Transient Impairments in Cognitive Function During Acute Bouts of Hypoxia.

INTRODUCTION: Exposure to low oxygen environments (hypoxia) can impair cognitive function; however, the time-course of the transient changes in cognitive function is unknown. In this study, we assessed cognitive function with a cognitive test before, during, and after exposure to hypoxia.METHODS: Nine participants (28 4 yr, 7 women) completed Conners Continuous Performance Test (CCPT-II) during three sequential conditions: 1) baseline breathing room air (fraction of inspired oxygen, FIo₂ 0.21); 2) acute hypoxia (FIo₂ 0.118); and 3) recovery after exposure to hypoxia. End-tidal gas concentrations (waveform capnography), heart rate (electrocardiography), frontal lobe tissue oxygenation (near infrared spectroscopy), and mean arterial pressure (finger photoplethysmography) were continuously assessed.RESULTS: Relative to baseline, during the hypoxia trial end-tidal (-30%) and cerebral (-9%) oxygen saturations were reduced. Additionally, the number of commission errors during the CCPT-II was greater during hypoxia trials than baseline trials (2.6 0.4 vs. 1.9 0.4 errors per block of CCPT-II). However, the reaction time and omission errors did not differ during the hypoxia CCPT-II trials compared to baseline CCPT-II trials. During the recovery CCPT-II trials, physiological indices of tissue hypoxia all returned to baseline values and number of commission errors during the recovery CCPT-II trials was not different from baseline CCPT-II trials.DISCUSSION: Oxygen concentrations were reduced (systemically and within the frontal lobe) and commission errors were increased during hypoxia compared to baseline. These data suggest that frontal lobe hypoxia may contribute to transient impairments in cognitive function during short exposures to hypoxia.Uchida K, Baker SE, Wiggins CC, Senefeld JW, Shepherd JRA, Trenerry MR, Buchholtz ZA, Clifton HR, Holmes DR, Joyner MJ, Curry TB. A novel method to measure transient impairments in cognitive function during acute bouts of hypoxia. Aerosp Med Hum Perform. 2020; 91(11):839844.

Prediction of the Effectiveness of Spontaneous Breathing in Patients with Brain Damage of Various Etiologies.

The aim of the study was to develop an informative method for assessing chemoreflex sensitivity and to evaluate its prognostic capacity for restoring spontaneous breathing in patients with brain damage of various etiologies. The study included 16 healthy volunteers and 38 patients on prolonged mechanical ventilation (VE) after a traumatic brain injury, anoxic brain damage, and cerebrovascular events. The external respiration variables were assessed from the initial level to the development of the first episode of desaturation with spO2 in the range of 90–80% against the background of normobaric hypoxia as indicators reflecting the development of adaptive ventilatory response and characterizing the state of peripheral chemoreflex sensitivity (PCS). The peripheral chemoreflex sensitivity index (PCSI) was calculated using the equation: PCSI = [RR(e) : RR(i)] × [Vt(e) : Vt(i)] × [VE(e) : VE(i)] × Vt(e) × VE(e), where PCSI is the peripheral chemoreflex sensitivity index in L2/min; RR(i) and RR(e); Vt(i) and Vt(e); VE(i) and VE(e) are the respiratory rate, tidal volume, minute ventilation initially (i), before a functional stress test, and during a functional test of normobaric hypoxia with spO2 in the range of 90–80% (e). With the PCSI values ≥15.6 L2/min, successful weaning from ventilators and recovery of spontaneous breathing are predicted. The sensitivity and specificity of PCSI were 78.57 [95% CI: 49.2–95.26] and 83.3% [95% CI: 62.6–95.26], respectively. The sensitivity and specificity of the traditional indicator of the success rate of weaning from ventilators and recovery of spontaneous breathing, Rapid Shallow Breathing Index (RSBI), in this cohort of patients was 69.23 [95% CI: 38.6–90.9] and 28.0% [95% CI: 12.03–49.3], respectively. A predictor of the patient’s weaning from mechanical ventilation is the assessment of peripheral chemoreflex sensitivity, which can be measured by a simple non-invasive bedside test based on measuring the difference in external ventilation parameters before and during a functional normobaric hypoxic trial.

Oxygen consumption during and post-hypoxia exposure in bearded fireworms (Annelida: Amphinomidae).

Oxygen is necessary for all marine animals to support metabolic functions. When chronic low dissolved oxygen (DO) conditions occur, organisms must adjust to overcome this stressor's effect on metabolic rates. The bearded fireworm, Hermodice carunculata, is a widespread species frequently exposed to hypoxic conditions in areas within its broad distribution which may impact metabolism, wound healing, and regeneration. To study the impact of hypoxia on their metabolic rates, we exposed fireworms to two levels of lower than normal DO conditions (low 2.5 ± 0.25mg O2 L-1 and mid 4.5 ± 0.25mg O2 L-1) for 7days by pumping nitrogen into their holding tanks. During a chronic hypoxia trial, we quantified oxygen consumption in each experimental group and subsequently determined post-hypoxia oxygen consumption of individuals from the lowest oxygen level. During the hypoxic exposure, the oxygen uptake rates declined in low and mid DO conditions, while remaining relatively constant for the normoxic (7.0 ± 0.25mg O2 L-1) control. We then compared the oxygen consumption rates from the lowest DO condition to fireworms likely never exposed to hypoxia and fireworms from a location likely to be exposed to hypoxia. We found higher oxygen consumption rates in the experimentally hypoxia-exposed worms. These results suggest prolonged negative impacts of hypoxic exposure, leading to a lasting elevation of metabolic rates of these marine invertebrates. The increase in metabolic rates may lead to increased predation on their prey of choice, economically and commercially important coral, causing increased degradation of already threatened coral reef ecosystems.

KATP channels modulate cerebral blood flow and oxygen delivery during isocapnic hypoxia in humans.

ATP-sensitive K+ (KATP ) channels mediate hypoxia-induced cerebral vasodilatation and hyperperfusion in animals. We tested whether KATP channels blockade affects the increase in human cerebral blood flow (CBF) and the maintenance of oxygen delivery (CDO2 ) during hypoxia. Hypoxia-induced increases in the anterior circulation and total cerebral perfusion were attenuated under KATP channels blockade affecting the relative changes of brain oxygen delivery. Therefore, in humans, KATP channels activation modulates the vascular tone in the anterior circulation of the brain, contributing to CBF and CDO2 responses to hypoxia. ATP-sensitive K+ (KATP ) channels mediate hypoxia-induced cerebral vasodilatation and hyperperfusion in animals. We tested whether KATP channels blockade affects the increase in cerebral blood flow (CBF) and the maintenance of oxygen delivery (CDO2 ) during hypoxia in humans. Nine healthy men were exposed to 5-min trials of normoxia and isocapnic hypoxia (IHX, 10% O2 ) before (BGB) and 3h after glibenclamide ingestion (AGB). Mean arterial pressure (MAP), arterial saturation ( ), partial pressure of oxygen ( ) and carbon dioxide ( ), internal carotid artery blood flow (ICABF), vertebral artery blood flow (VABF), total (t)CBF (Doppler ultrasound) and CDO2 were quantified during the trials. IHX provoked similar reductions in and , while MAP was not affected by oxygen desaturation or KATP blockade. A smaller increase in ICABF (ΔBGB: 36±23 vs. ΔAGB 11±18%, p=0.019) but not in VABF (∆BGB 26±21 vs. ∆AGB 27±27%, p=0.893) was observed during the hypoxic trial under KATP channels blockade. Thus, IHX-induced increases in tCBF (∆BGB 32±19 vs. ∆AGB 14±13%, p=0.012) and CDO2 relative changes (∆BGB 7±13 vs. ∆AGB -6±14%, p=0.048) were attenuated during the AGB hypoxic trial. In a separate protocol, 6 healthy men (5 from protocol 1) underwent a 5-min exposure to normoxia and IHX before and 3h after placebo (5mg of cornstarch) ingestion. IHX reduced and , but placebo did not affect the ICABF, VABF, tCBF, or CDO2 responses. Therefore, in humans, KATP channels activation modulates vascular tone in the anterior rather than the posterior circulation of the brain, contributing to tCBF and CDO2 responses to hypoxia.

No effect of supplemented heat stress during an acute endurance exercise session in hypoxia on hepcidin regulation.

The purpose of the present study was to compare endurance exercise-induced hepcidin elevation among "normoxia", "hypoxia" and "combined heat and hypoxia". Twelve males (21.5 ± 0.3years, 168.1 ± 1.2cm, 63.6 ± 2.0kg) participated in the present study. They performed 60min of cycling at 60% of [Formula: see text] in either "heat and hypoxia" (HHYP; FiO2 14.5%, 32°C), "hypoxia" (HYP; FiO2 14.5%, 23°C) or "normoxia" (NOR; FiO2 20.9%, 23°C). After completing the exercise, participants remained in the prescribed conditions for 3h post-exercise. Blood samples were collected before, immediately and 3h after exercise. Plasma IL-6 level significantly increased immediately after exercise (P < 0.05), with no significant difference among the trials. A significant elevation in serum EPO was observed 3h after exercise in hypoxic trials (HHYP and HYP, P < 0.05), with no significant difference between HHYP and HYP. Serum hepcidin level increased 3h after exercise in all trials (NOR, before 18.3 ± 3.9 and post180 31.2 ± 6.3ng/mL; HYP, before 13.5 ± 2.5 and post180 23.3 ± 3.6ng/mL, HHYP; before 15.8 ± 3.3 and post180 31.4 ± 5.3ng/mL, P < 0.05). However, there was no significant difference among the trials during post-exercise. Endurance exercise in "combined heat and hypoxia" did not exacerbate exercise-induced hepcidin elevation compared with the same exercise in "hypoxia" or "normoxia".

Influence of muscle oxygenation and nitrate-rich beetroot juice supplementation on O2 uptake kinetics and exercise tolerance

We tested the hypothesis that acute supplementation with nitrate (NO3−)-rich beetroot juice (BR) would improve quadriceps muscle oxygenation, pulmonary oxygen uptake (V˙O2) kinetics and exercise tolerance (Tlim) in normoxia and that these improvements would be augmented in hypoxia and attenuated in hyperoxia. In a randomised, double-blind, cross-over study, ten healthy males completed two-step cycle tests to Tlim following acute consumption of 210 mL BR (18.6 mmol NO3−) or NO3−-depleted beetroot juice placebo (PL; 0.12 mmol NO3−). These tests were completed in normobaric normoxia [fraction of inspired oxygen (FIO2): 21%], hypoxia (FIO2: 15%) and hyperoxia (FIO2: 40%). Pulmonary V˙O2 and quadriceps tissue oxygenation index (TOI), derived from multi-channel near-infrared spectroscopy, were measured during all trials. Plasma [nitrite] was higher in all BR compared to all PL trials (P < 0.05). Quadriceps TOI was higher in normoxia compared to hypoxia (P < 0.05) and higher in hyperoxia compared to hypoxia and normoxia (P < 0.05). Tlim was improved after BR compared to PL ingestion in the hypoxic trials (250 ± 44 vs. 231 ± 41 s; P = 0.006; d = 1.13), with the magnitude of improvement being negatively correlated with quadriceps TOI at Tlim (r = −0.78; P < 0.05). Tlim was not improved following BR ingestion in normoxia (BR: 364 ± 98 vs. PL: 344 ± 78 s; P = 0.087, d = 0.61) or hyperoxia (BR: 492 ± 212 vs. PL: 472 ± 196 s; P = 0.273, d = 0.37). BR ingestion increased peak V˙O2 in hypoxia (P < 0.05), but not normoxia or hyperoxia (P > 0.05). These findings indicate that BR supplementation is more likely to improve Tlim and peak V˙O2 in situations when skeletal muscle is more hypoxic.

Sex Differences in Response to Acute Sympathetic Activation During Steady State Hypoxia

BackgroundActivation of the sympathetic nervous system causes vasoconstriction and a reduction in peripheral blood flow. This sympathetically‐mediated vasoconstriction may be attenuated during hypoxia to maintain oxygen delivery – termed sympatholysis. However, hypoxic sympatholysis was previously shown to be absent in humans. A limitation of prior work was the failure to directly examine this response in women. Given young women exhibit an increase in blood flow during hypoxia, we hypothesized hypoxic sympatholysis would be present in young women but absent in young men.MethodsBlood pressure (BP, finger photoplethysmography) and forearm blood flow (FBF, venous occlusion plethysmography) were assessed in healthy young men (n=9, 26±1 yrs) and women (n=10, 24±1 yrs). Subjects completed two trials consisting of a 2‐min cold pressor test (CPT) during baseline normoxia (0.21 FiO2, 98±0% SpO2) and following 3 min of steady‐state hypoxia (0.11±0.01 FiO2, 82±1% SpO2). FBF was normalized for BP (forearm vascular conductance, FVC). A change in FVC from steady‐state during the last 1‐min of CPT was calculated (ΔFVC). The difference in ΔFVC between normoxia and hypoxia trials was used as an index of hypoxic sympatholysis.ResultsIn men, ΔFVC did not differ between normoxia and hypoxia (ΔFVC Normoxia: −0.30±0.45, Hypoxia: −0.77±0.41 mL/dL/100mmHg/min; p=0.46). In contrast, in women ΔFVC during normoxia (−0.70±0.27 mL/dL/100mmHg/min) was attenuated during hypoxia (+0.48±0.46 mL/dL/100mmHg/min; p=0.04) – indicating sympatholysis. The magnitude of hypoxic sympatholysis was greater in women than in men (Men: −0.46±0.38, Women: +1.18±0.39 mL/dL/100mmHg/min; p&lt;0.01).ConclusionYoung women attenuate sympathetically‐mediated vasoconstriction during steadystate hypoxia, whereas men do not. In other words, hypoxic sympatholysis is present in young women, but absent in young men. These data advance our understanding of sex‐related differences in hypoxic vascular control.Support or Funding InformationFundingNIH HL130339

Hypertension impairs hypoxia-induced angiogenesis in men.

The inability of the organism to appropriately respond to hypoxia results in abnormal cell metabolism and function. Hypoxia-induced angiogenesis seems to be suppressed in experimental models of hypertension; however, this hypothesis has not been tested in humans. We examined changes in endothelial biomarkers and vascular chemoattraction/angiogenic capacity in response to isocapnic hypoxia in hypertensive men. Twelve normotensive (38 ± 10 years) and nine hypertensive men (45 ± 11 years) were exposed to 5-min trials of normoxia (21% O2) and isocapnic hypoxia (10% O2). During the last minute of each trial, venous blood was drawn. Endothelial progenitor cells (EPCs; CD45/CD34/VEGFR2), endothelial microvesicles (apoptotic EMVs, CD42b/CD31/AnnexinV; endothelial activation, CD62E/CD144), nitrite, vascular endothelial growth factor (VEGF), and stromal cell-derived factor 1 (SDF-1) were measured. During normoxia, EPCs, nitrite, endothelial activation, and SDF-1 were similar between groups, whereas VEGF was lower (P = 0.02) and apoptotic EMVs tended to increase (P = 0.07) in hypertensive men. During isocapnic hypoxia, endothelial activation increased in both groups (normotensive, P = 0.007 vs. normoxia; hypertensive, P = 0.006 vs. normoxia), whereas EMVs were higher only in the hypertensive group (P = 0.03 vs. normotensive). EPCs (P = 0.01 vs. normoxia; P = 0.03 vs. hypertensive men), NO (P = 0.01 vs. normoxia; P = 0.04 vs. hypertensive), and VEGF (P = 0.02 vs. normoxia; P = 0.0005 vs. hypertensive) increased only in normotensive individuals in response to isocapnic hypoxia. SDF-1 did not change in either group. These results suggest that hypertension-induced impairment in angiogenesis in response to isocapnic hypoxia is related to disrupted NO bioavailability, VEGF chemotactic signaling, and EPC mobilization.