Hypoxia augments apnea-induced increase in hemoglobin concentration and hematocrit

Increased hemoglobin concentration (Hb) and hematocrit (Hct), attributable to spleen contraction, raise blood gas storage capacity during apnea, but the mechanisms that trigger this response have not been clarified. We focused on the role of hypoxia in triggering these Hb and Hct elevations. After horizontal rest for 20 min, 10 volunteers performed 3 maximal apneas spaced by 2 min, each preceded by a deep inspiration of air. The series was repeated using the same apneic durations but after 1 min of 100% oxygen (O₂) breathing and O₂ inspiration prior to each apnea. Mean apneic durations were 150, 171, and 214 s for apneas 1, 2, and 3, respectively. Relative to pre-apnea values, the mean post-apneic arterial O₂ saturation nadir was 84.7% after the air trial and 98% after the O₂ trial. A more pronounced elevation of both Hb and Hct occurred during the air trial: after apnea 1 with air, mean Hb had increased by 1.5% (P < 0.01), but no clear increase was found after the first apnea with O₂. After the third apnea with air Hb had increased by 3.0% (P < 0.01), and with O₂ by 2.0% (P < 0.01). After the first apnea with air Hct had increased by 1.9% (P < 0.01) and after 3 apneas by 3.0% (P < 0.01), but Hct did not change significantly in the O₂ trial. In both trials, Hb and Hct were at pre-apneic levels 10 min after apneas. Diving bradycardia during apnea was the same in both trials. We conclude that hypoxia contributes to spleen contraction during apnea, likely through chemosensor-related sympathetic output. There are, however other factors involved that trigger spleen contraction even in the absence of hypoxia.     

Hypoxia ameliorates brain hyperoxia and NAD+ deficiency in a murine model of Leigh syndrome

Leigh syndrome is a severe mitochondrial neurodegenerative disease with no effective treatment. In the Ndufs4^?/? mouse model of Leigh syndrome, continuously breathing 11% O₂ (hypoxia) prevents neurodegeneration and leads to a dramatic extension (~5-fold) in lifespan. We investigated the effect of hypoxia on the brain metabolism of Ndufs4^?/? mice by studying blood gas tensions and metabolite levels in simultaneously sampled arterial and cerebral internal jugular venous (IJV) blood. Relatively healthy Ndufs4^?/? and wildtype (WT) mice breathing air until postnatal age ~38 d were compared to Ndufs4^?/? and WT mice breathing air until ~38 days old followed by 4-weeks of breathing 11% O₂. Compared to WT control mice, Ndufs4^?/? mice breathing air have reduced brain O₂ consumption as evidenced by an elevated partial pressure of O₂ in IJV blood (P_ijvO₂) despite a normal PO₂ in arterial blood, and higher lactate/pyruvate (L/P) ratios in IJV plasma revealed by metabolic profiling. In Ndufs4^?/? mice, hypoxia treatment normalized the cerebral venous P_ijvO₂ and L/P ratios, and decreased levels of nicotinate in IJV plasma. Brain concentrations of nicotinamide adenine dinucleotide (NAD⁺) were lower in Ndufs4^?/? mice breathing air than in WT mice, but preserved at WT levels with hypoxia treatment. Although mild hypoxia (17% O₂) has been shown to be an ineffective therapy for Ndufs4^?/? mice, we find that when combined with nicotinic acid supplementation it provides a modest improvement in neurodegeneration and lifespan. Therapies targeting both brain hyperoxia and NAD⁺ deficiency may hold promise for treating Leigh syndrome.     

The effect of hypoxia on performance during 30 s or 45 s of supramaximal exercise

Summary The purpose of this study was to evaluate the effect of hypoxia (10.8±0.6% oxygen) on performance of 30 s and 45 s of supramaximal dynamic exercise. Twelve males were randomly allocated to perform either a 30 s or 45 s Wingate test (WT) on two occasions (hypoxia and room air) with a minimum of 1 week between tests. After a 5-min warm-up at 120 W subjects breathed the appropriate gas mixture from a wet spirometer during a 5-min rest period. Resting blood oxygen saturation was monitored with an ear oximeter and averaged 97.8 ± 1.5% and 83.2 ± 1.9% for the air (normoxic) and hypoxic conditions, respectively, immediately prior to the WT. Following all WT trials, subjects breathed room air for a 10-min passive recovery period. Muscle biopsies from the vastus lateralis were taken prior to and immediately following WT. Arterialized blood samples, for lactate and blood gases, were taken before and after both the warm-up and the performance of WT, and throughout the recovery period. Opencircuit spirometry was used to calculate the total oxygen consumption (Vo₂), carbon dioxide production and expired ventilation during WT. Hypoxia did not impair the performance of the 30-s or 45-s WT.Vo₃ was reduced during the 45-s hypoxic WT (1.71±0.21 I) compared with the normoxic trial (2.16±0.261), but there was no change during the 30-s test (1.22±0.11 vs 1.04±0.171 for the normoxic and hypoxic conditions, respectively). Muscle lactate (LA) increased more during hypoxia following both the 30-s and 45-s WT (67.1±25.0 mmol· kg^–1 dry weight) compared with normoxia (30.8 ± 18.0 mmol · kg^–1 dry weight). Hypoxia did not influence the change in intramuscular adenosine triphosphate, creatine phosphate and glucose-6-phosphate. The performance of WT during hypoxia was associated with a greater decrease in muscle glycogen (P<0.06). Throughout the recovery period, blood LA was lower following the hypoxia (8.43±2.88 mmol · l^–1) comparedwith normoxia (9.15±3.06 mmol · 1^–1). Breathing the hypoxic gas mixture prior to the performance of WT increased blood pH to 7.44±0.03, compared with 7.39±0.03 for normoxia. Blood pH remained higher during the 10-min recovery period following the hypoxic WT trials (7.24±0.08) compared with the normoxic WT (7.22±0.06). BloodP _{CO 2} was reduced prior to and immediately following WT during hypoxia, but there were no differences between the normoxic and hypoxic trials during the 10 min recovery period. These data indicate that more energy was transduced from the catabolism of glycogen to lactate during the hypoxic WT trials, which offset the reduced O₂ availability and maintained performance comparable with normoxic conditions. It is suggested that the induced respiratory alkalosis associated with breathing the hypoxic gas could account for the increased rate of muscle LA accumulation.     

Reproducibility of the alterations in circulation and cerebral oxygenation from supine rest to head-up tilt.

Cardiovascular stability, as affected by several diseases, may be assessed by head-up tilt testing. Follow-up studies are essential in both evaluating interventions and assessing progression. However, data on the reproducibility of the changes in circulatory status and cerebral oxygenation provoked by head-up tilt testing are fundamental to follow-up studies. The aim of this study was, therefore, to assess the reproducibility of the alterations in stroke volume (SV), mean arterial pressure (MAP), as well as oxygenated ([O2Hb]) and deoxygenated haemoglobin ([HHb]) concentration in cerebral tissue from supine rest (SUP) to head-up tilt (HUT). SV was calculated by Modelflow, a pulse contour method, from the finger arterial pressure wave measured by Portapres, the portable version of Finapres. [O2Hb] and [HHb] were measured using near-infrared spectroscopy (NIRS). Ten healthy individuals visited the laboratory on two different days. On both days, they underwent 10 min SUP followed by 10 min 70 degrees HUT twice. SV decreased, which was (in part) compensated for by an increased heart rate, while MAP increased slightly during HUT compared with SUP. Although [HHb] increased during HUT, no presyncope symptoms were experienced. The circulatory variables (SV, HR and MAP) as well as [HHb] showed an acceptably small systematic and random error as well as reproducibility error compared with the observed difference between HUT and SUP and were similar between and within visits. Therefore, it is concluded that MAP measured by Portapres and SV calculated by Modelflow as well as HHb measured by NIRS seem to be reproducible and may therefore be used in follow-up studies.     

Hypocapnia-dependent facilitation of augmented breaths: observations in awake vs. anesthetized rats

We investigated whether commonly used injectable laboratory anesthetics alter the regulation of augmented breaths (ABs) in different respiratory backgrounds. Male rats were studied on three separate experimental days, receiving one of three injections in randomized order: ethyl carbamate (‘urethane’; 1.2 mg kg⁻¹), ketamine/xylazine (ket/xyl; 80/10 mg kg⁻¹), or normal saline. Following each of the three interventions, breathing was monitored during 15 min exposures to normoxia (room air), hypoxia (10% O₂) and hypoxia + CO₂ (10% O₂, 5% CO₂). Urethane anesthesia completely eliminated ABs from the breathing rhythm in room air conditions (p < 0.001), and decreased the hypocapnia-dependent component of this response (p < 0.001). ket/xyl left the normal incidence of ABs in room air breathing intact but significantly suppressed the hypoxia-induced facilitation of ABs (p = 0.0015). These results provide the first clear evidence that laboratory anesthesia can profoundly alter the regulation of ABs including the hypocapnia-dependent component of their facilitation.     

The effects of hypoxia and CO2 on the sleep-waking pattern of the potoroo (Potorous tridactylus apicalis)

Four male potoroos (Potorous tridactylus apicalis) breathed 21% and 7% O₂ with and without the addition of 5% CO₂. The effects of these gas mixtures on the potoroo's sleeping-waking pattern (SWP) were studied. The SWP while breathing 21% O₂/5%CO₂ was unchanged when compared with that of breathing ambient air (21% O₂). While breathing 7% O₂, the SWP was severely disrupted: total sleep time (TST) and slow wave sleep (SWS) increased markedly. Brain temperature fell substantially. Paradoxical sleep (PS) was almost abolished and wakefulness (W) decreased. The addition of 5% CO₂ to the O₂ deficient gas mixture, i.e., 7% O₂/5% CO₂, restored the SWP to that obtained while breathing ambient air. It is concluded that CO₂ neutralizes the disruptive effect which hypoxia has on the potoroo's SWP. It is hypothesized that this constitutes a homeostatic mechanism for stabilizing the SWP and is carried over from pouch life.     

Hypoxia-induced ventilatory responses in conscious mice: Gender differences in ventilatory roll-off and facilitation

The aim of this study was to compare the ventilatory responses of C57BL6 female and male mice during a 15 min exposure to a hypoxic–hypercapnic (H–H) or a hypoxic (10% O₂, 90% N₂) challenge and subsequent return to room air. The ventilatory responses to H–H were similar in males and females whereas there were pronounced gender differences in the ventilatory responses during and following hypoxic challenge. In males, the hypoxic response included initial increases in minute volume via increases in tidal volume and frequency of breathing. These responses declined substantially (roll-off) during hypoxic exposure. Upon return to room-air, relatively sustained increases in these ventilatory parameters (short-term potentiation) were observed. In females, the initial responses to hypoxia were similar to those in males whereas roll-off was greater and post-hypoxia facilitation was smaller than in males. The marked differences in ventilatory roll-off and post-hypoxia facilitation between female and male C57BL6 mice provide evidence that gender is of vital importance to ventilatory control.     

Rapidity of responding to a hypoxic challenge during exercise

The ability to modify power output (PO) in response to a changing stimulus during exercise is crucial for optimizing performance involving an integration system involving a performance template and feedback from peripheral receptors. The rapidity with which PO is modified has not been established, but would be of interest relative to understanding how PO is regulated. The objective is to determine the rapidity of changes in PO in response to a hypoxic challenge, and if change in PO is linked to changes in arterial O₂ saturation (S _aO₂). Well-trained cyclists performed randomly ordered 5-km time trials. Subjects began the trials breathing room air and switched to hypoxic (HYPOXIC, F_IO₂ = 0.15) or room (CONTROL, F_IO₂ = 0.21) air at 2 km, then to room air at 4 km. The time delay to begin decreasing S _aO₂ and PO and to recover S _aO₂ and PO on to room air was compared, along with the half time (t _1/2) during the HYPOXIC trial. Mean S _aO₂ and PO between 2 and 4 km were significantly different between CONTROL and HYPOXIC (94 ± 2 vs. 83 ± 2% and 285 ± 16 vs. 245 ± 19 W, respectively). There was no difference between the time delay for S _aO₂ (31.5 ± 12.8 s) and in PO (25.8 ± 14.4 s) or the recovery of S _aO₂ (29.0 ± 7.7 s) and PO (21.5 ± 12.4 s). The half time for decreases in S _aO₂ (56.6 ± 14.4 s) and in PO (62.7 ± 20.8 s) was not significantly different. Modifications of PO due to the abrupt administration of hypoxic air are related to the development of arterial hypoxemia, and begin within ~30 s.     

Human erythropoietin response to hypocapnic hypoxia,normocapnic hypoxia,and hypocapnic normoxia

This study investigated the human erythropoietin (EPO) response to short-term hypocapnic hypoxia, its relationship to a normoxic or hypoxic increase of the haemoglobin oxygen affinity, and its suppression by the addition of CO₂ to the hypoxic gas. On separate days, eight healthy male subjects were exposed to 2 h each of hypocapnic hypoxia, normocapnic hypoxia, hypocapnic normoxia, and normal breathing of room air (control experiment). During the control experiment, serum-EPO showed significant variations (ANOVAP = 0.047) with a 15% increase in mean values. The serum-EPO measured in the other experiments were corrected for these spontaneous variations in each individual. At 2 h after ending hypocapnic hypoxia (10% O₂ in nitrogen), mean serum-EPO increased by 28% [baseline 8.00 (SEM 0.84) U · 1⁻¹, post-hypoxia 10.24 (SEM 0.95) U · 1⁻¹, P = 0.005]. Normocapnic hypoxia was produced by the addition of CO₂ (10% Co₂ with 10% O₂) to the hypoxic gas mixture. This elicited an increased ventilation, unaltered arterial pH and haemoglobin oxygen affinity, a lower degree of hypoxia than during hypocapnic hypoxia, and no significant changes in serum-EPO (ANOVAP > 0.05). Hypocapnic normoxia, produced by hyperventilation of room air, elicited a normoxic increase in the haemoglobin oxygen affinity without changing serum-EPO. Among the measured blood gas and acid-base parameters, only the partial pressures of oxygen in arterial blood during hypocapnic hypoxia were related to the peak values of serum-EPO (r = −0.81,P = 0.01). The present human EPO responses to hypoxia were lower than those which have previously been reported in rodents and humans. In contrast with the earlier rodent studies, it was found that human EPO production could not be triggered by short-term increases in pH and haemoglobin oxygen affinity per se, and the human EPO response to hypoxia could be suppressed by concomitant normocapnia without acidosis.     

Estimation of Alveolar Po2

“Mean alveolar” Po₂ calculated from the alveolar gas equation, using arterial P_cO2, was compared with the corresponding end-expired P_O2, measured with a rapidly responding O₂ electrode (τ= 0.05 si and with arterial Po₂. 12 healthy subjects (WO₂max 1.8–3.6 1/min) were studied at rest supine and during rest and exercise in the sitting position, breathing air and 12 %O₂. Differences between end-expired and mean alveolar Po values were small and statistically insignificant during exercise while breathing air and during hypoxia at rest, both sitting and supine. Exercise during hypoxia resulted in lower end-expired than mean alveolar values. At rest breathing air the end-expired values were higher, especially in the sitting position (12 mm Hg). The results are compatible with the assumption of non-synchronous emptying of alveoli, combined with exercise- and gravity dependent regional differences in alveolar P_O2- From simultaneous measurements of arterial P_co2 it is inferred that the end-expired Po₂ approximates the time- and volume weighted mean of alveolar Po₂ only at high rates of exercise, breathing air.     

Hypoxia and CO alter O2 extraction but not peripheral diffusing capacity during maximal aerobic exercise

Purpose

To determine if and how hypoxia combined with elevated carboxyhaemoglobin fraction (F _HbCO) affects peripheral diffusing capacity and O₂ extraction in animals exercising at their maximal aerobic capacity ( $ \dot{V}{\text{O}}_{ 2\hbox{max} } $ ).

Methods

Six goats ran on a treadmill at speeds eliciting $ \dot{V}{\text{O}}_{ 2\hbox{max} } $ while breathing inspired O₂ fractions (F _IO₂) of 0.21 or 0.12 with F _HbCO 0.02 or 0.30. We measured O₂ consumption and arterial and mixed-venous blood variables to assess how hypoxia and elevated F _HbCO individually, and in combination, alter O₂ transport and utilisation.

Results

Peripheral diffusing capacity did not differ among the four gas combinations (P = 0.867), whereas O₂ extraction fraction increased with hypoxia [0.920 ± 0.018 (SD)] and decreased with elevated F _HbCO (0.792 ± 0.038) compared to control (0.897 ± 0.032). Oxygen extraction increases with hypoxia due to the sigmoid relationship between O₂ saturation (SO₂) and O₂ partial pressures (PO₂) affecting low (hypoxia) and high (normoxia) PO₂ differently. Oxygen extraction decreases with elevated F _HbCO because elevated F _HbCO increases haemoglobin (Hb) affinity for O₂ and raises SO₂, especially at very low (mixed-venous) PO₂. Pulmonary gas exchange was impaired only with combined hypoxia and elevated F _HbCO due to hypoxia decreasing alveolar PO₂ and O₂ flux coupled with elevated F _HbCO increasing Hb affinity for O₂ and decreasing the rate of PO₂ increase for a given rise in SO₂.

Conclusion

This study quantifies the mechanisms by which O₂ delivery and peripheral diffusion interact to limit $ \dot{V}{\text{O}}_{ 2\hbox{max} } $ when O₂ delivery is reduced due to breathing hypoxic gas with elevated F _HbCO.     

G proteins in rat prefrontal cortex (PFC) are differentially activated as a function of oxygen status and PFC region

This study tested the hypothesis that activation of guanine nucleotide binding (G) proteins in rat prefrontal cortex (PFC) is altered by hypoxia. G protein activation by the cholinergic agonist carbachol and the opioid agonist DAMGO was quantified using [³⁵S]GTPγS autoradiography. G protein activation was expressed as nCi/g tissue in the PFC of 18 rats exposed for 14 consecutive days to sustained hypoxia (10% O₂), intermittent hypoxia (10% and 21% O₂ alternating every 90 s), or room air (21% O₂). Relative to basal levels of G protein activation, carbachol and DAMGO increased G protein activation by approximately 70% across all oxygen concentrations. Compared to the room air condition, sustained hypoxia caused a significant increase in G protein activation in frontal association (FrA) region of the PFC. Region-specific comparisons revealed that intermittent and sustained hypoxia caused greater DAMGO-stimulated G protein activation in the FrA than in the pre-limbic (PrL). The data show for the first time that hypoxia increased G protein activation in PFC. The results suggest the potential for hypoxia-induced enhancements in G protein activation to alter PFC function.     

The effect of acute exercise in hypoxia on flow-mediated vasodilation

The purpose of this study was to clarify the effect of acute exercise in hypoxia on flow-mediated vasodilation (FMD). Eight males participated in this study. Two maximal exercise tests were performed using arm cycle ergometry to estimate peak oxygen uptake $ \left( {\dot{V}{\text{O}}_{{ 2 {\text{peak}}}} } \right) $ while breathing normoxic [inspired O₂ fraction (FIO₂) = 0.21] or hypoxic (FIO₂ = 0.12) gas mixtures. Next, subjects performed submaximal exercise at the same relative exercise intensity $ \left( {30\,\% \;\dot{V}{\text{O}}_{{ 2 {\text{peak}}}} } \right) $ in normoxia or hypoxia for 30 min. Before (Pre) and after exercise (Post 5, 30, and 60 min), brachial artery FMD was measured during reactive hyperemia by ultrasound under normoxic conditions. FMD was estimated as the percent (%) rise in the peak diameter from the baseline value at prior occlusion at each FMD measurement (%FMD). The area under the curve for the shear rate stimulus (SR_AUC) was calculated in each measurement, and each %FMD value was normalized to SR_AUC (normalized FMD). %FMD and normalized FMD decreased significantly (P < 0.05) immediately after exercise in both condition (mean ± SE, FMD, normoxic trial, Pre: 8.85 ± 0.58 %, Post 5: ?0.01 ± 1.30 %, hypoxic trial, Pre: 8.84 ± 0.63 %, Post 5: 2.56 ± 0.83 %). At Post 30 and 60, %FMD and normalized FMD returned gradually to pre-exercise levels in both trials (FMD, normoxic trial, Post 30: 1.51 ± 0.68 %, Post 60: 2.99 ± 0.79 %; hypoxic trial, Post 30: 4.57 ± 0.78 %, Post 60: 6.15 ± 1.20 %). %FMD and normalized FMD following hypoxic exercise (at Post 5, 30, and 60) were significantly (P < 0.05) higher than after normoxic exercise. These results suggest that aerobic exercise in hypoxia has a significant impact on endothelial-mediated vasodilation.     

Endurance exercise performance in acute hypoxia is influenced by expiratory flow limitation

Purpose

We sought to determine if expiratory flow limitation influences intensive aerobic exercise performance in mild hypoxia.

Methods

Fourteen trained male cyclists were separated into flow-limited (FL, n = 7) and non-FL (n = 7) groups based on the extent of expiratory flow limitation exhibited during maximal exercise in normoxia. Participants performed two self-paced 5-km cycling time trials, one in normoxic (F _IO₂ = 0.21) and one in mild hypoxic (F _IO₂ = 0.17) conditions in a randomized, balanced order with the subjects blinded to composition of the inspirate. Percent change from normoxia to hypoxia in average power output (%ΔP _TT) and time to completion (%ΔT _TT) were used to assess performance.

Results

Hypoxia resulted in a significant decline in estimated arterial O₂ saturation and decrements in performance in both groups, although FL had a significantly smaller %ΔP _TT (?4.0 ± 0.5 vs. ?9.0 ± 1.8 %) and %ΔT _TT (1.3 ± 0.3 vs. 3.7 ± 0.9 %) compared to non-FL. At the 5th km of the time trial, minute ventilation did not change from normoxia to hypoxia in FL (3.4 ± 3.1 %) or non-FL (2.3 ± 3.7 %), but only the non-FL reported a significantly increased dyspnea rating in hypoxia compared to normoxia (~9 %). Non-FL athletes did not utilize their ventilatory reserve to defend arterial oxygen saturation in hypoxia, which may have been due to an increased measure of dyspnea in the hypoxic trial.

Conclusion

FL athletes experience less hypoxia-related aerobic exercise performance impairment as compared to non-FL athletes, despite having less ventilatory reserve.

     

Effect of acute hypoxia on muscle blood flow, VO2p, and [HHb] kinetics during leg extension exercise in older men

The adjustment of pulmonary oxygen uptake (VO_2p), heart rate (HR), limb blood flow (LBF), and muscle deoxygenation [HHb] was examined during the transition to moderate-intensity, knee-extension exercise in six older adults (70 ± 4 years) under two conditions: normoxia (FIO₂ = 20.9 %) and hypoxia (FIO₂ = 15 %). The subjects performed repeated step transitions from an active baseline (3 W) to an absolute work rate (21 W) in both conditions. Phase 2 VO_2p, HR, LBF, and [HHb] data were fit with an exponential model. Under hypoxic conditions, no change was observed in HR kinetics, on the other hand, LBF kinetics was faster (normoxia 34 ± 3 s; hypoxia 28 ± 2), whereas the overall [HHb] adjustment ( $ \tau^{\prime } = {\text{TD}} + \tau $ ) was slower (normoxia 28 ± 2; hypoxia 33 ± 4 s). Phase 2 VO_2p kinetics were unchanged (p < 0.05). The faster LBF kinetics and slower [HHb] kinetics reflect an improved matching between O₂ delivery and O₂ utilization at the microvascular level, preventing the phase 2 VO_2p kinetics from become slower in hypoxia. Moreover, the absolute blood flow values were higher in hypoxia (1.17 ± 0.2 L min^?1) compared to normoxia (0.96 ± 0.2 L min^?1) during the steady-state exercise at 21 W. These findings support the idea that, for older adults exercising at a low work rate, an increase of limb blood flow offsets the drop in arterial oxygen content (CaO₂) caused by breathing an hypoxic mixture.     

Relationship among nausea,anxiety, and orthostatic symptoms in pediatric patients with chronic unexplained nausea

This study evaluated the relationship among nausea, anxiety, and orthostatic symptoms in pediatric patients with chronic unexplained nausea. We enrolled 48 patients (36 females) aged 15 ± 2 years. Patients completed the Nausea Profile, State-Trait Anxiety Inventory for Children and underwent 70° head upright tilt testing (HUT) to assess for orthostatic intolerance (OI) and measure heart rate variability (HRV). We found nausea to be significantly associated with trait anxiety, including total nausea score (r = 0.71, p < 0.01) and 3 subscales: somatic (r = 0.64, p < 0.01), gastrointestinal (r = 0.48, p = 0.01), and emotional (r = 0.74, p < 0.01). Nausea was positively associated with state anxiety, total nausea (r = 0.55, p < 0.01), somatic (r = 0.48, p < .01), gastrointestinal (r = .30, p < .05), and emotional (r = .64, p < .01) subscales. Within 10 min of HUT, 27 patients tested normal and 21 demonstrated OI. After 45 min of HUT, only 13 patients (27 %) remained normal. Nausea reported on the Nausea Profile before HUT was associated with OI measured at 10 min of tilt (nausea total r = 0.35, p < 0.05; nausea emotional subscale r = 0.40, p < 0.01) and lower HRV at 10 min of HUT (F = 6.39, p = 0.01). We conclude that nausea is associated with both anxiety symptoms and OI. The finding of decreased HRV suggests an underlying problem in autonomic nervous system function in children and adolescents with chronic unexplained nausea.     

Indirect measures of human vagal withdrawal during head-up tilt with and without a respiratory acidosis

Human ECG records were analyzed during supine (SUP) rest and whole body 80° head-up tilt (HUT), with a respiratory acidosis (5%CO₂) and breathing room air (RA). HUT increased heart rate in both conditions (RA_SUP 60 ± 13 vs. RA_HUT 79 ± 16; 5%CO_2SUP 63 ± 12 vs. 5%CO_2HUT 79 ± 14 beats min⁻¹) and decreased mean R–R interval, with no changes in the R–R interval standard deviation. When corrected for changes in frequency spectrum total power (NU), the high frequency (0.15–0.4 Hz) component (HF_NU) of heart rate variability decreased (RA_SUP 44.01 ± 21.57 vs. RA_HUT 24.05 ± 13.09; 5%CO_2SUP 69.23 ± 15.37 vs. 5%CO_2HUT 47.64 ± 21.11) without accompanying changes in the low frequency (0.04–0.15 Hz) component (LF_NU) (RA_SUP 52.36 ± 21.93 vs. RA_HUT 66.58 ± 19.49; 5%CO_2SUP 22.97 ± 11.54 vs. 5%CO_2HUT 40.45 ± 21.41). Positive linear relations between the tilt-induced changes (Δ) in HF_NU and R–R interval were recorded for RA (ΔHF_NU = 0.0787(ΔR−R) − 11.3, R ² = 0.79, P < 0.05), and for 5%CO₂ (ΔHF_NU = 0.0334(ΔR−R) + 1.1, R ² = 0.82, P < 0.05). The decreased HF component suggested withdrawal of vagal activity during HUT. For both RA and 5%CO₂, the positive linear relations between ΔHF_NU and ΔR−R suggested that the greater the increase in heart rate with HUT, the greater the vagal withdrawal. However, a reduced range of ΔHF during HUT with respiratory acidosis suggested vagal withdrawal was lower with a respiratory acidosis.     

The effect of normocapnic hypoxia and the duration of exposure to hypoxia on supramaximal exercise performance

Summary Two investigations were designed that (a) evaluated the effect of the respiratory alkalosis that accompanies breathing an hypoxic (H) gas mixture and (b) examined the influence of the duration of breathing this H mixture on the subsequent performance of 45 s supramaximal dynamic exercise. In experiment 1, 12 men performed a 45-s Wingate Test (WT) on three occasions breathing a normoxic (N; 20.9% 02), H (11.3% 02), or normocapnic hypoxic (H + CO₂; 11.5070 O₂, 2.25% CO₂) gas mixture for 20 min prior to performing the WT. For experiment 2, nine men performed a 20-min normoxic (N20) and three hypoxic WT trials which consisted of breathing an 11070 O₂ balance N₂ gas mixture for 10 min (H10), 20 min (H20) or 30 min (H30) prior to the WT. For experiment 1,VO₂ was significantly reduced during the 45-s H [mean (SD); 1.22 (0.23) 1] and H + CO₂ [1.12 (0.18)1] trials compared with the N trial [1.78 (0.18) 1]. Peak power output (W _peak) during WT was similar across trials. However, a small (less than 3070) but significant reduction in the mean power output (W) was observed in both the H and H + CO₂ trials [6.8 (0.6) W · kg^–1] compared with the N trial [7.0 (0.6) W · kg^–1]. Prior to performing the WT, blood pH andPCO₂ were similar [7.40 (0.02) and 5.3 (0.3) kPa, respectively] for the N and H + CO₂ trials. A respiratory alkalosis accompanied the H condition [7.46 (0.02) for pH and 4.6 (0.3) kPa forPCO₂. For experiment 2,VO₂ also was significantly lower during the 45-s WT for H10 [1.16 (0.16) 1], H2O [1.17 (0.16)1], and H30 [1.18 (0.26) 1] compared with N20 [1.84 (0.41) 1].W _peak was similar across trials but a significant reduction in meanW was observed again for the H trials [7.1 (0.4) W · kg^–1] compared with N20 [7.4 (0.4) W · kg^–1]. These data conflict with our previous findings and suggest that breathing an 11% H gas mixture will reduce the mean power produced during 45 s of supramaximal exercise.     

Age and hypothyroidism affect dopamine modulation of breathing and D2 receptor levels

During and following hypoxic exposure young male hypothyroid hamsters treated with the dopamine D₂ receptor agonist bromocriptine increased breathing, while ventilation was depressed in bromocriptine-treated euthyroid hamsters. Moreover, D₂ receptor expression was increased in carotid bodies and striatum, but not in the nucleus tractus solitaries (NTS) of hypothyroid relative to euthyroid hamsters. Here ventilation was determined in older male hypothyroid and euthyroid hamsters given vehicle or bromocriptine, and exposed to baseline air, hypoxia, and then air. Bromocriptine without hypoxia served as a time control. Relative to vehicle, bromocriptine depressed ventilation in both groups exposed to air or to hypoxia, but hypothyroid bromocriptine-treated hamsters increased ventilatory responsiveness to hypoxia, while euthyroid hamsters decreased ventilatory responsiveness to hypoxia and exhibited post-hypoxic depression. Hypothyroidism had no effect on D₂ receptor expression in carotid bodies or striatum, but increased it in the NTS. Thus, in hamsters bromocriptine modulates breathing and expression of D₂ receptor depending on the length of hypothyroidism.     

Quantitative BOLD response of the renal medulla to hyperoxic challenge at 1.5 T and 3.0 T

The aim of this study was to gage the magnitude of changes of the apparent renal medullary transverse relaxation time (ΔT₂*) induced by inhalation of pure oxygen (O₂) or carbogen (95% O₂, 5% CO₂) versus baseline breathing of room air. Eight healthy volunteers underwent 2D multi‐gradient echo MR imaging at 1.5 T and 3.0 T. Parametrical T₂* relaxation time maps were computed and average T₂* was measured in regions of interest placed in the renal medulla and cortex. The largest T₂* changes were measured in the renal medulla, with a relative ?T₂* of 33.8 ± 22.0% (right medulla) and 34.7 ± 17.6% (left medulla) as compared to room air for oxygen breathing (p > 0.01), and 53.8 ± 23.9% and 53.5 ± 33.9% (p < 0.01) for carbogen breathing, respectively at 3 T. At 1.5 T, the corresponding values were 13.7 ± 18.5% and 24.1 ± 17.1% (p < 0.01) for oxygen breathing and 23.9 ± 17.2% and 38.9 ± 37.6% (p < 0.01) for carbogen breathing. As a result, we showed that renal medullary T₂* times responded strongly to inhalation of hyperoxic gases, which may be attributed to the hypoxic condition of the medulla and subsequent reduction in deoxyhemoglobin. Copyright © 2012 John Wiley & Sons, Ltd.