The middle cerebral artery blood velocity response to acute normobaric hypoxia occurs independently of changes in ventilation in humans.

NEW FINDINGS: What is the central question of this study? Does the ventilatory response to moderate acute hypoxia increase cerebral perfusion independently of changes in arterial oxygen tension in humans? What is the main finding and its importance? The ventilatory response does not increase middle cerebral artery mean blood velocity during moderate isocapnic acute hypoxia beyond that elicited by reduced oxygen saturation. ABSTRACT: Hypoxia induces ventilatory, cardiovascular and cerebrovascular adjustments to defend against reductions in systemic oxygen delivery. We aimed to determine whether the ventilatory response to moderate acute hypoxia increases cerebral perfusion independently of changes in arterial oxygenation. Eleven young healthy individuals were exposed to four 15 min experimental conditions: (1) normoxia (partial pressure of end-tidal oxygen, PETO2  = 100 mmHg), (2) hypoxia ( PETO2  = 50 mmHg), (3) normoxia with breathing volitionally matched to levels observed during hypoxia (hyperpnoea; PETO2  = 100 mmHg) and (4) hypoxia ( PETO2  = 50 mmHg) with respiratory frequency and tidal volume volitionally matched to levels observed during normoxia (i.e., restricted breathing (RB)). Isocapnia was maintained in all conditions. Middle cerebral artery mean blood velocity (MCA Vmean ), assessed by transcranial Doppler ultrasound, was increased during hypoxia (58 ± 12 cm/s, P = 0.04) and hypoxia + RB (61 ± 14 cm/s, P < 0.001) compared to normoxia (55 ± 11 cm/s), while it was unchanged during hyperpnoea (52 ± 13 cm/s, P = 0.08). MCA Vmean was not different between hypoxia and hypoxia + RB (P > 0.05). These findings suggest that the hypoxic ventilatory response does not increase cerebral perfusion, indexed using MCA Vmean , during moderate isocapnic acute hypoxia beyond that elicited by reduced oxygen saturation.

Isolating the independent effects of hypoxia and hyperventilation-induced hypocapnia on cerebral haemodynamics and cognitive function.

NEW FINDINGS: What is the central question of this study? What are the independent effects of hypoxia and hypocapnia on cerebral haemodynamics and cognitive function? What is the main finding and its importance? Exposure to hyperventilation-induced hypocapnia causes cognitive impairment in both normoxia and hypoxia. In addition, supplementation of carbon dioxide during hypoxia alleviates the cognitive impairment and reverses hypocapnia-induced vasoconstriction of the cerebrovasculature. These data provide new evidence for the independent effect of hypocapnia on the cognitive impairment associated with hypoxia. ABSTRACT: Hypoxia, which is accompanied by hypocapnia at altitude, is associated with cognitive impairment. This study examined the independent effects of hypoxia and hypocapnia on cognitive function and assessed how changes in cerebral haemodynamics may underpin cognitive performance outcomes. Single reaction time (SRT), five-choice reaction time (CRT) and spatial working memory (SWM) tasks were completed in 20 participants at rest and after 1 h of isocapnic hypoxia (IH, end-tidal oxygen partial pressure ( PETO2 ) = 45 mmHg, end-tidal carbon dioxide partial pressure ( PETCO2 ) clamped at normal) and poikilocapnic hypoxia (PH, PETO2  = 45 mmHg, PETCO2 not clamped). A subgroup of 10 participants were also exposed to euoxic hypocapnia (EH, PETO2  = 100 mmHg, PETCO2 clamped 8 mmHg below normal). Middle cerebral artery velocity (MCAv) and prefrontal cerebral haemodynamics were measured with transcranial Doppler and near infrared spectroscopy, respectively. IH did not affect SRT and CRT performance from rest (566 ± 50 and 594 ± 70 ms), whereas PH (721 ± 51 and 765 ± 48 ms) and EH (718 ± 55 and 755 ± 34 ms) slowed response times (P < 0.001 vs. IH). Performance on the SWM task was not altered by condition. MCAv increased during IH compared to PH (P < 0.05), which was unchanged from rest. EH caused a significant fall in MCAv and prefrontal cerebral oxygenation (P < 0.05 vs. baseline). MCAv was moderately correlated to cognitive performance (R2  = 0.266-0.289), whereas prefrontal cerebral tissue perfusion and saturation were not (P > 0.05). These findings reveal a role of hyperventilation-induced hypocapnia per se on the development of cognitive impairment during normoxic and hypoxic exposures.

Sensitivity of the human ventilatory response to muscle metaboreflex activation during concurrent mild hypercapnia.

NEW FINDINGS: What is the central question of this study? What is the relationship between the level of systemic hypercapnia and the magnitude of the additional hyperpnoea produced in response to a standardized level of muscle metaboreflex activation? What is the main finding and its importance? When a standardized activation of the muscle metaboreflex was combined with exposure to increasing levels of hypercapnia, the hyperpnoea this caused increased linearly. The concept of a synergistic interaction between the muscle metaboreflex and the central chemoreflex in humans is supported by this finding. ABSTRACT: Ventilation increases during muscle metaboreflex activation when postexercise circulatory occlusion (PECO) traps metabolites in resting human muscle, but only in conditions of concurrent systemic hypercapnia. We hypothesize that a linear relationship exists between the level of hypercapnia and the magnitude of the additional hyperpnoea produced in response to a standardized level of muscle metaboreflex activation. Fifteen male subjects performed four trials, in which the end-tidal partial pressure of carbon dioxide ( P ET , C O 2 ) was elevated by 1, 3, 7 or 10 mmHg above resting values using a dynamic end-tidal forcing system. In each trial, subjects were seated in an isometric dynamometer designed to measure ankle plantar flexor force. Rest for 2 min in room air was followed by 15 min of exposure to one of the four levels of hypercapnia, at which 5 min further rest was followed by 2 min of sustained isometric calf muscle contraction at 50% of predetermined maximal voluntary strength. Immediately before cessation of exercise, a cuff around the upper leg was inflated to a suprasystolic pressure to cause PECO for 3 min, before its deflation and a further 5 min of rest, concluding exposure to hypercapnia. The PECO consistently elevated mean arterial blood pressure by ∼10 mmHg in all trials, indicating similar levels of metaboreflex activation. Increased ventilation during PECO was related to P ET , C O 2 as described by the following linear regression equation: Change in minute ventilation (l min-1 ) = 0.85 ×  P ET , C O 2 (mmHg) + 0.80 (l min-1 ). This finding supports our hypothesis and furthers the idea of a synergistic interaction between muscle metaboreflex activation and central chemoreflex stimulation.

Undiagnosed Obstructive Sleep Apnea and Physical Activity in Older Manual Workers.

Cardiovascular disease is a negative health outcome of obstructive sleep apnea (OSA). Risk factors associated with OSA development include low physical activity (PA), high body mass index (BMI), and increasing age (>50 years), and weight loss is usually recommended as treatment. This cross-sectional study examined the association between PA, BMI, and OSA severity in manual workers. Fifty-five participants (23 females and 32 males; mean age 55.2 years), were examined for OSA and completed a PA and anthropometric assessment. On average, OSA severity was mild, PA levels were moderate, and 32% of the sample was classified as obese. PA was negatively associated with OSA severity, but BMI strongly independently predicted OSA severity, with no evidence of mediation. As both PA and BMI were significantly associated with OSA in older manual workers, increasing PA should also be a focus of treatment for OSA.

Frequency-domain vs continuous-wave near-infrared spectroscopy devices: a comparison of clinically viable monitors in controlled hypoxia.

The Near-infrared spectroscopy (NIRS) has not been adopted as a mainstream monitoring modality in acute neurosurgical care due to concerns about its reliability and consistency. However, improvements in NIRS parameter recovery techniques are now available that may improve the quantitative accuracy of NIRS for this clinical context. Therefore, the aim of this study was to compare the abilities of a continuous-wave (CW) NIRS device with a similarly clinically viable NIRS device utilising a frequency-domain (FD) parameter recovery technique in detecting changes in cerebral tissue saturation during stepwise increases of experimentally induced hypoxia. Nine healthy individuals (6M/3F) underwent a dynamic end-tidal forced manipulation of their expiratory gases to induce a stepwise induced hypoxia. The minimum end-tidal oxygen partial pressure (EtO2) achieved was 40 mm Hg. Simultaneous neurological and extra-cranial tissue NIRS reading were obtained during this protocol by both tested devices. Both devices detected significant changes in cerebral tissue saturation during the induction of hypoxia (CW 9.8 ± 2.3 %; FD 7.0 ± 3.4 %; Wilcoxon signed rank test P < 0.01 for both devices). No significant difference was observed between the saturation changes observed by either device (P = 0.625). An observably greater degree of noise was noticed in parameters recovered by the FD device, and both demonstrated equally variable baseline readings (Coefficient of variance 8.4 and 9.7 % for the CW and FD devices, respectively) between individuals tested. No advantageous difference was observed in parameters recovered from the FD device compared with those detected by CW.

Muscle metaboreflex and cerebral blood flow regulation in humans: implications for exercise with blood flow restriction.

We investigated the effect of activating metabolically sensitive skeletal muscle afferents (muscle metaboreflex) on cerebral blood flow and the potentially confounding influence of concomitant changes in the partial pressure of arterial carbon dioxide. Eleven healthy males (25 ± 4 yr) performed submaximal leg cycling exercise on a semirecumbent cycle ergometer (heart rate: ∼120 beats/min), and assessments were made of the partial pressure of end-tidal carbon dioxide (PetCO2 ), internal carotid artery blood flow (ICAQ) and conductance (ICACVC), and middle cerebral artery mean blood velocity (MCAvm) and conductance index (MCACVCi).The muscle metaboreflex was activated during cycling with leg blood flow restriction (BFR) or isolated with postexercise ischemia (PEI). In separate trials, PetCO2 was either permitted to fluctuate spontaneously (control trial) or was clamped at 1 mmHg above resting levels (PetCO2 clamp trial). In the control trial, leg cycling with BFR decreased PetCO2 (Δ-4.8 ± 0.9 mmHg vs. leg cycling exercise) secondary to hyperventilation, while ICAQ, ICACVC, and MCAvm were unchanged and MCACVCi decreased. However, in the PetCO2 clamp trial, leg cycling with BFR increased both MCAvm (Δ5.9 ± 1.4 cm/s) and ICAQ (Δ20.0 ± 7.8 ml/min) and attenuated the decrease in MCACVCi, while ICACVC was unchanged. In the control trial, PEI decreased PetCO2 (Δ-7.0 ± 1.3 mmHg vs. rest), MCAvm and MCACVCi, whereas ICAQ and ICACVC were unchanged. In contrast, in the PetCO2 clamp trial both ICAQ (Δ18.5 ± 11.9 ml/min) and MCAvm (Δ8.8 ± 2.0 cm/s) were elevated, while ICACVC and MCACVCi were unchanged. In conclusion, when hyperventilation-related decreases in PetCO2 are prevented the activation of metabolically sensitive skeletal muscle afferent fibers increases cerebral blood flow.

Exaggerated pulmonary vascular response to acute hypoxia in older men.

NEW FINDINGS: What is the central question of this study? Pulmonary arterial pressure is higher in older than younger humans and predicts mortality. It is also increased by acute hypoxia, which causes constriction of the pulmonary vasculature. We asked whether this pulmonary vascular response to hypoxia is greater in older humans. What is the main finding and its importance? Using Doppler echocardiography in 12 younger (∼ 20 years old) and nine older men (∼ 55 years old) exposed to 20 min of moderate isocapnic hypoxia, we demonstrated that older men showed a significantly greater rise in pulmonary arterial pressure during alveolar hypoxia than younger men. Future studies should examine the pathophysiological importance of increased hypoxic pulmonary vasoconstriction with age. Resting pulmonary arterial pressure increases with age in humans. In the general population, higher values are associated with increased mortality, and in common cardiopulmonary diseases, such as congestive heart failure and chronic obstructive pulmonary disease, the presence of pulmonary arterial hypertension portends a worse outcome. Pulmonary arterial pressure increases during alveolar hypoxia, as a consequence of constriction in the pulmonary vasculature. We hypothesized that older men have more vigorous hypoxic pulmonary vasoconstriction than younger men. Twelve younger (20.5 ± 0.5 years old) and nine older men (55.8 ± 2.1 years old) were exposed for 20 min on different days to isocapnic hypoxia (end-tidal PO2 = 50 mmHg) and isocapnic euoxia (end-tidal PO2 = 100 mmHg); each was preceded (baseline) and followed by 5 min of isocapnic euoxia. Systolic pulmonary arterial pressure and cardiac output were measured continuously using Doppler echocardiography. Systolic pulmonary arterial pressure was greater during baseline euoxic measurements in older participants (27.8 ± 0.8 versus 24.1 ± 0.7 mmHg, P = 0.001) and also increased more during hypoxia in older participants (15.2 ± 1.3 versus 9.6 ± 0.9 mmHg, P = 0.011). Cardiac output did not differ between the two groups during baseline measurements (P = 0.60) or hypoxia (P = 0.49). All data are means ± SEM. The increased magnitude of hypoxic pulmonary vasoconstriction demonstrated with age has implications for individuals wishing to ascend to high altitude or travel by air, for those suffering from conditions in which global alveolar hypoxia is a feature and for patients requiring general anaesthesia.

Influence of muscle metaboreceptor stimulation on middle cerebral artery blood velocity in humans.

Regional anaesthesia to attenuate skeletal muscle afferent feedback abolishes the exercise-induced increase in middle cerebral artery mean blood velocity (MCA Vmean). However, such exercise-related increases in cerebral perfusion are not preserved during post exercise muscle ischaemia (PEMI) where the activation of metabolically sensitive muscle afferents is isolated. We tested the hypothesis that a hyperventilation-mediated decrease in the arterial partial pressure of CO2, hence cerebral vasoconstriction, masks the influence of muscle metaboreceptor stimulation on MCA Vmean during PEMI. Ten healthy men (20 ± 1 years old) performed two trials of fatiguing isometric hand-grip exercise followed by PEMI, in control conditions and with end-tidal CO2 (P ET ,CO2) clamped at ∼1 mmHg above the resting partial pressure. In the control trial, P ET ,CO2 decreased from rest during hand-grip exercise and PEMI, while MCA Vmean was unchanged from rest. By design, P ET ,CO2 remained unchanged from rest throughout the clamp trial, while MCA Vmean increased during hand-grip (+10.6 ±1.8 cm s(-1)) and PEMI (+9.2 ± 1.6 cm s(-1); P < 0.05 versus rest and control trial). Increases in minute ventilation and mean arterial pressure during hand-grip and PEMI were not different in the control and P ET ,CO2 clamp trials (P > 0.05). These findings indicate that metabolically sensitive skeletal muscle afferents play an important role in the regional increase in cerebral perfusion observed in exercise, but that influence can be masked by a decrease in P ET ,CO2 when they are activated in isolation during PEMI.

The pulmonary vascular response to combined activation of the muscle metaboreflex and mechanoreflex.

Muscle metabo- and mechanoreflexes are known to influence systemic cardiovascular responses to exercise. Whether interplay between these reflexes is operant in the control of the pulmonary vascular response to exercise is unknown. The aim of this study was to assess the pulmonary vascular response to the combined activation of the two muscle reflexes. Nine healthy subjects performed a bout of isometric calf plantarflexion exercise during local circulatory occlusion, which was continued for 9 min postexercise (PECO). At 5 min into PECO the calf muscle was passively stretched for 180 s. A control (no exercise) protocol was also undertaken. Heart rate, blood pressure measurements and echocardiographically determined estimates of systolic pulmonary artery pressure (SPAP) and cardiac output ( ) were obtained at intervals throughout the two protocols. Elevations in SPAP (by 22.51 ± 2.61%), (by 26.92 ± 2.99%) and mean arterial pressure (by 15.38 ± 2.29%) were noted during isometric exercise in comparison to baseline (all P < 0.05). Increases in SPAP and mean arterial pressure persisted during PECO (All P < 0.05), whereas returned to resting levels. These increases in mean arterial pressure and SPAP were sustained during stretch which significantly elevated (All P < 0.05). These data suggest that activation of the muscle mechanoreflex attenuated the increases in pulmonary vascular resistance caused by metaboreflex activation. This finding has important implications for the regulation of pulmonary haemodynamics during human exercise.

Long-term facilitation of ventilation following acute continuous hypoxia in awake humans during sustained hypercapnia.

In awake humans, long-term facilitation of ventilation (vLTF) following acute intermittent hypoxia (AIH) is only expressed if CO2 is maintained above normocapnic levels. vLTF has not been reported following acute continuous hypoxia (ACH) and it is not known whether this might be unmasked by elevated CO2. Twelve healthy participants completed three trials. In all trials end-tidal pressure of CO2 was elevated 4-5 mmHg above normocapnic levels. During Trial 1 (AIH) participants were exposed to eight 4 min episodes of hypoxia. During Trial 2 (ACH) participants were exposed to continuous hypoxia for 32 min. In Trial 3 (Control) participants were exposed to euoxia throughout. To assess the contribution of the carotid body (CB) in observed ventilatory responses, CB afferent discharge before and after each trial was transiently inhibited with hyperoxia. Minute ventilation ( ˙V E) increased following all trials, but was significantly greater in Trials 1 and 2 when compared with Trial 3 (Trial 1: 4.96 ± 0.87, Trial 2: 5.07 ± 0.7, Trial 3: 2.55 ± 0.98 l min-1, P < 0.05). Hyperoxia attenuated VE to a similar extent in baseline and recovery in all trials (Trial 1: 3.0 ± 0.57 vs. 3.27 ± 0.68, Trial 2: 1.97 ± 0.62 vs. 2.56 ± 0.62, Trial 3: 2.23 ± 0.49 vs. 2.15 ± 0.55 l min-1, P > 0.05). Data are means ± SEM. In awake humans with elevated CO2, ACH evokes a sustained increase in ventilation that is comparable to that evoked by AIH. However, a gradual positive drift in ventilation in response to elevated CO2 accounts for approximately half of this apparent vLTF. Additionally, our data support the view that the CB is not directly involved in maintaining vLTF.

Sleep spindles track cortical learning patterns for memory consolidation.

Memory consolidation-the transformation of labile memory traces into stable long-term representations-is facilitated by post-learning sleep. Computational and biophysical models suggest that sleep spindles may play a key mechanistic role for consolidation, igniting structural changes at cortical sites involved in prior learning. Here, we tested the resulting prediction that spindles are most pronounced over learning-related cortical areas and that the extent of this learning-spindle overlap predicts behavioral measures of memory consolidation. Using high-density scalp electroencephalography (EEG) and polysomnography (PSG) in healthy volunteers, we first identified cortical areas engaged during a temporospatial associative memory task (power decreases in the alpha/beta frequency range, 6-20 Hz). Critically, we found that participant-specific topographies (i.e., spatial distributions) of post-learning sleep spindle amplitude correlated with participant-specific learning topographies. Importantly, the extent to which spindles tracked learning patterns further predicted memory consolidation across participants. Our results provide empirical evidence for a role of post-learning sleep spindles in tracking learning networks, thereby facilitating memory consolidation.

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.

Sex differences in carotid baroreflex control of arterial blood pressure in humans: relative contribution of cardiac output and total vascular conductance.

It is presently unknown whether there are sex differences in the magnitude of blood pressure (BP) responses to baroreceptor perturbation or if the relative contribution of cardiac output (CO) and total vascular conductance (TVC) to baroreflex-mediated changes in BP differs in young women and men. Since sympathetic vasoconstrictor tone is attenuated in women, we hypothesized that carotid baroreflex-mediated BP responses would be attenuated in women by virtue of a blunted vascular response (i.e., an attenuated TVC response). BP, heart rate (HR), and stroke volume were continuously recorded during the application of 5-s pulses of neck pressure (NP; carotid hypotension) and neck suction (NS; carotid hypertension) ranging from +40 to -80 Torr in women (n = 20, 21 ± 0.5 yr) and men (n = 20, 21 ± 0.4 yr). CO and TVC were calculated on a beat-to-beat basis. Women demonstrated greater depressor responses to NS (e.g., -60 Torr, -17 ± 1%baseline in women vs. -11 ± 1%baseline in men, P < 0.05), which were driven by augmented decreases in HR that, in turn, contributed to larger reductions in CO (-60 Torr, -15 ± 2%baseline in women vs. -6 ± 2%baseline in men, P < 0.05). In contrast, pressor responses to NP were similar in women and men (e.g., +40 Torr, +14 ± 2%baseline in women vs. +10 ± 1%baseline in men, P > 0.05), with TVC being the primary mediating factor in both groups. Our findings indicate that sex differences in the baroreflex control of BP are evident during carotid hypertension but not carotid hypotension. Furthermore, in contrast to our hypothesis, young women exhibited greater BP responses to carotid hypertension by virtue of a greater cardiac responsiveness.

Is the beneficial effect of prior exercise on postprandial lipaemia partly due to redistribution of blood flow?

Preprandial aerobic exercise lowers postprandial lipaemia (a risk factor for coronary heart disease); however, the mechanisms responsible are still not clear. The present study investigated whether blood flow to skeletal muscle and/or the liver was increased in the postprandial period after exercise, relative to a control trial, and whether this resulted from increased cardiac output or redistribution of flow. Eight overweight inactive males, aged 49.4±10.5 years (mean±S.D.), acted as their own controls in a counterbalanced design, either walking briskly for 90 min at 60% V̇O2max (maximal oxygen uptake), or resting in the lab, on the evening of day 1. The following morning, a fasting blood sample was collected, participants consumed a high-fat breakfast, and further venous blood samples were drawn hourly for 6 h. Immediately after blood sampling, Doppler ultrasound was used to measure cardiac output and blood flow through both the femoral artery of one leg and the hepatic portal vein, with the ultrasonographer blinded to trial order. The total postprandial triacylglycerol response was 22% lower after exercise (P=0.001). Blood flow through the femoral artery and the hepatic portal vein was increased by 19% (P<0.001) and 16% (P=0.033), respectively, during the 6-h postprandial period following exercise; however, postprandial cardiac output did not differ between trials (P=0.065). Redistribution of blood flow, to both exercised skeletal muscle and the liver, may therefore play a role in reducing the plasma triacylglycerol response to a high-fat meal on the day after an exercise bout.

Does sleep-dependent consolidation favour weak memories?

Sleep stabilizes newly acquired memories, a process referred to as memory consolidation. According to recent studies, sleep-dependent consolidation processes might be deployed to different extents for different types of memories. In particular, weaker memories might benefit greater from post-learning sleep than stronger memories. However, under standard testing conditions, sleep-dependent consolidation effects for stronger memories might be obscured by ceiling effects. To test this possibility, we devised a new memory paradigm (Memory Arena) in which participants learned temporospatial arrangements of objects. Prior to a delay period spent either awake or asleep, training thresholds were controlled to yield relatively weak or relatively strong memories. After the delay period, retrieval difficulty was controlled via the presence or absence of a retroactive interference task. Under standard testing conditions (no interference), a sleep-dependent consolidation effect was indeed observed for weaker memories only. Critically though, with increased retrieval demands, sleep-dependent consolidation effects were seen for both weaker and stronger memories. These results suggest that all memories are consolidated during sleep, but that memories of different strengths require different testing conditions to unveil their benefit from post-learning sleep.

A respiratory response to the activation of the muscle metaboreflex during concurrent hypercapnia in man.

In this study, we aimed to assess the ventilatory and cardiovascular responses to the combined activation of the muscle metaboreflex and the ventilatory chemoreflex, achieved by postexercise circulatory occlusion (PECO) and euoxic hypercapnia (end-tidal partial pressure of CO2 7 mmHg above normal), respectively. Eleven healthy subjects (4 women and 7 men; 29 +/- 4.4 years old; mean +/- S.D.) undertook the following four trials, in random order: 2 min of isometric handgrip exercise followed by 2 min of PECO with hypercapnia; 2 min of isometric handgrip exercise followed by 2 min of PECO while breathing room air; 4 min of rest with hypercapnia; and 4 min of rest while breathing room air. Ventilation was significantly increased during exercise in both the hypercapnic (+3.17 +/- 0.82 l min(-1)) and the room air breathing trials (+2.90 +/- 0.26 l min(-1); all P < 0.05). During PECO, ventilation returned to pre-exercise levels when breathing room air (+0.52 +/- 0.37 l min(-1); P > 0.05), but it remained elevated during hypercapnia (+3.77 +/- 0.23 l min(-1); P < 0.05). The results indicate that the muscle metaboreflex stimulates ventilation with concurrent chemoreflex activation. These findings have implications for disease states where effort intolerance and breathlessness are linked.

The implementation of a physical activity intervention in adults with Obstructive Sleep Apnoea over the age of 50 years: a feasibility uncontrolled clinical trial.

BACKGROUND: Obstructive Sleep Apnoea (OSA) is a risk factor for cardiovascular disease (CVD) and Type 2 diabetes (T2D). Observational studies suggested that OSA treatment might reduce CVD and T2D but RCTs failed to support these observations in part due to poor adherence to continuous positive airway pressure (CPAP). Physical activity (PA) has been shown to have favourable impact on CVD and the risk of T2D independent of its impact on weight and therefore might provide additional health gains to patients with OSA, whether or not adherent to CPAP. METHODS: The main aim of this study was to explore the feasibility of providing a 12-week PA intervention to adults aged over 50 with OSA. The secondary aim was to assess the impact of the PA intervention on OSA severity. Patients with moderate-severe OSA (apnoea hypopnea index (AHI) ≥ 15 events/hour (based on overnight ApneaLink™) were recruited in response to posters displayed in workplaces. A 12-week daily PA intervention was delivered in participant's home setting and PA was monitored via text and validated by objective PA measures (GT3X accelerometers). RESULTS: The intervention was feasible as all 10 patients (8 males, mean (SD) age 57.3 (6.01)) completed the intervention and PA increased across the 12-weeks. The duration of PA increased from baseline (113.1 min (64.69) per week to study-end following the intervention (248.4 min (148.31) (p = 0.02). Perceived Exertion (RPE) (physical effort) increased significantly between baseline (M = 10.7 (1.94)) to end of intervention (M = 13.8, (1.56) (p < 0.001). The intervention had no significant impact on weight or composition. Following the intervention, there was a statistically non-significant a reduction in AHI from baseline to study end (22.3 (7.35) vs. 15.8 (7.48); p = 0.09). CONCLUSION: It is feasible to deliver a PA intervention to adults aged over 50 with OSA. The intervention resulted in improved PA and AHI levels somewhat and seemingly independent of weight changes. Future trials need to examine whether PA can reduce the burden of OSA associated comorbidities. TRIAL REGISTRATION: CTN: ISRCTN11016312 Retrospectively Registered 21/07/20.

Quantitative fMRI using hyperoxia calibration: reproducibility during a cognitive Stroop task.

Arterial spin labelling allows simultaneous measurement of both the blood-oxygenation-level-dependent (BOLD) and the cerebral blood flow (CBF) response to changes in neural activity. The addition of a hypercapnia or hyperoxia calibration allows additional quantification of changes in the cerebral metabolic rate of oxygen (CMRO(2)). In this study we test the reproducibility of measurements derived using the hyperoxia approach, during a cognitive Stroop task. A QUIPSSII sequence is used at 3 T to collect simultaneous CBF and BOLD signal during two 3 min periods of hyperoxia and an 8 min Stroop task. Hyperoxia was administered via an open system and end-tidal values were sampled via a nasal cannula; average end-tidal values of 60% were reached. This procedure is repeated to allow the reproducibility of the estimated parameters to be tested. The use of a cognitive Stroop task allows testing of the measurements in frontal and parietal regions as well as sensorimotor areas in which previous studies have been focussed. We find reduced reproducibility of the calculated parameters compared to the hypercapnia approach, thought to be attributable to lower absolute BOLD and CBF responses. In particular we do not find 'n' to have improved reproducibility compared to other parameters, as has been found in previous work using the hypercapnia approach. Across all brain areas we report a value of DeltaCMRO(2) of 12% and neurovascular coupling constant n of 2.5. Interestingly we find n to be higher in parietal and frontal areas in comparison to the primary motor cortex.

Diurnal Variations in Vascular Endothelial Vasodilation Are Influenced by Chronotype in Healthy Humans.

Introduction: The time of day when cardiovascular events are most likely to occur is thought to be aligned with the circadian rhythm of physiological variables. Chronotype has been shown to influence the time of day when cardiovascular events happen, with early chronotypes reported to be more susceptible in the morning and late chronotypes in the evening. However, no studies have investigated the influence of chronotype on physiological variables responsible for cardiovascular regulation in healthy individuals. Methods: 312 individuals completed the Munich ChronoType Questionnaire to assess chronotype. Twenty participants were randomly selected to continue into the main study. In a repeated-measures experiment, participants were tested between 08:00 and 10:00 h and again between 18:00 and 20:00 h. Measurements of mean arterial pressure, heart rate and vascular endothelial vasodilation via flow-mediated dilatation (FMD) were obtained at each session. Results: Individual diurnal differences in mean arterial pressure and heart rate show no significant relationship with chronotype. Diurnal differences in FMD showed a significant correlation (p = 0.010), driven by a clear significant relationship in the evening and not the morning (p < 0.001). Conclusion: These preliminary data indicate that chronotype influences the diurnal variation of endothelial vasodilation measured using flow-mediated dilatation. Furthermore, we show that the influence of chronotype is much stronger in the evening, highlighting an increased susceptibility for later types. These findings are consistent with the diurnal rhythm in cardiovascular events and uncover potential mechanisms of local mediators that may underpin the influence of chronotype in the onset of these events.

An acute exposure to intermittent negative airway pressure elicits respiratory long-term facilitation in awake humans.

BACKGROUND: A sustained elevation in respiratory drive following removal of the inducing stimulus is known as respiratory long-term facilitation (rLTF). We investigated whether an acute exposure to intermittent negative airway pressure (INAP) elicits rLTF in humans. METHOD: 13 healthy males (20.9 ±â€¯2.8 years) undertook two trials (INAP and Control). In the INAP trial participants were exposed to one hour of 30-second episodes of breathing against negative pressure (-10 cmH2O) interspersed by 60-second intervals of breathing at atmospheric pressure. In the Control trial participants breathed at atmospheric pressure for one hour. Ventilation following INAP (recovery phase) was compared to that during baseline. RESULTS: Ventilation increased from baseline to recovery in the INAP trial (14.9 ±â€¯0.9 vs 19.1 ±â€¯0.7 L/min, P = 0.002). This increase was significantly greater than the equivalent during the Control trial (P = 0.019). Data shown as mean ± SEM. CONCLUSION: In this study INAP elicited rLTF in awake, healthy humans. Further research is required to investigate the responsible mechanisms.