Breathing Hyperoxic Gas Research Articles

Perceived Exertion And Dyspnea While Cycling During A Hypoxic And Hyperoxic Placebo

Rating of Perceived Exertion (RPE) is used to subjectively quantify and monitor the perception of physical activity, breathlessness or dyspnea, and leg discomfort (RPElegs) during exercise. However, it is unknown how perceptions of exertion can be influenced by expectation of difficulty. PURPOSE: We asked if the placebo and nocebo effects could alter dyspnea and RPEleg by telling subjects they were receiving different concentrations of oxygen during exercise. We hypothesized that subjects would rate their dyspnea and RPElegs higher when they believed they were breathing hypoxic gas and lower when they believed they were breathing hyperoxic gas relative to room air. METHODS: Thirty healthy, active subjects (19 M, 11 F) with normal pulmonary function participated. Prior to exercise, we read a script to ensure subjects understood hypoxic and hyperoxic gas might make breathing feel more difficult and easier, respectively, but intentionally made no mention about RPEleg. Then during 5-minute submaximal cycling trials (60% peak work rate), we deceived subjects by telling them they were breathing different hypoxic (17% and 15% O2) and hyperoxic (23% O2) gas concentrations, when in fact they breathed room air (21% O2). At the end of each trial, we asked subjects for their dyspnea and RPEleg. RESULTS: Cardiorespiratory variables were similar between the trials, however dyspnea and RPElegs changed in a dose-response manner depending on the O2 concentration participants believed they breathed. When subjects believed they were breathing 15% O2, they significantly increased their dyspnea +0.70 ± 0.2 Borg units (p = 0.03) compared to room air, whereas RPElegs did not significantly change +0.35 ± 0.1 Borg units (p = 0.70). When comparing the most severe hypoxic condition, 15% O2, to the 23% hyperoxic condition, subjects significantly increased their dyspnea +1.05 ± 0.4 Borg units (p = 0.003) but did not significantly change RPElegs + 0.55 ± 0.2 Borg units (p = 0.46). CONCLUSION: We found that dyspnea during exercise is susceptible to expectancy, without any accompanying physiological changes. Given that a single unit in dyspnea is considered a minimal clinically important difference, our findings show that the effect of expectation must be considered when interpreting sensations of breathlessness. Support: NSERC

Hyperoxia Improves Repeated-Sprint Ability and the Associated Training Load in Athletes.

This study investigated the impact of hyperoxic gas breathing (HYP) on repeated-sprint ability (RSA) and on the associated training load (TL). Thirteen team- and racquet-sport athletes performed 6-s all-out sprints with 24-s recovery until exhaustion (power decrement ≥ 15% for two consecutive sprints) under normoxic (NOR: FIO2 0.21) and hyperoxic (HYP: FIO2 0.40) conditions in a randomized, single-blind and crossover design. The following variables were recorded throughout the tests: mechanical indices, arterial O2 saturation (SpO2), oxygenation of the vastus lateralis muscle with near-infrared spectroscopy, and electromyographic activity of the vastus lateralis, rectus femoris, and gastrocnemius lateralis muscles. Session TL (work × rate of perceived exertion) and neuromuscular efficiency (work/EMG [Electromyography]) were calculated. Compared with NOR, HYP increased SpO2 (2.7 ± 0.8%, Cohen's effect size ES 0.55), the number of sprints (14.5 ± 8.6%, ES 0.28), the total mechanical work (13.6 ± 6.8%, ES 0.30), and the session TL (19.4 ± 7.0%, ES 0.33). Concomitantly, HYP increased the amplitude of muscle oxygenation changes during sprints (25.2 ± 11.7%, ES 0.36) and recovery periods (26.1 ± 11.4%, ES 0.37), as well as muscle recruitment (9.9 ± 12.1%, ES 0.74), and neuromuscular efficiency (6.9 ± 9.0%, ES 0.24). It was concluded that breathing a hyperoxic mixture enriched to 40% O2 improves the total work performed and the associated training load during an open-loop RSA session in trained athletes. This ergogenic impact may be mediated by metabolic and neuromuscular alterations.

High-altitude decompression strain can be reduced by an early excursion to moderate altitude while breathing oxygen

Recent observations suggest that development of venous gas emboli (VGE) during high-altitude flying whilst breathing hyperoxic gas will be reduced by intermittent excursions to moderate altitude. The present study aimed to investigate if an early, single excursion from high to moderate altitude can be used as an in-flight means to reduce high-altitude decompression strain. Ten healthy men were investigated whilst breathing oxygen in a hypobaric chamber under two conditions, once during a 90-min continuous exposure to a simulated cabin altitude of 24,000 ft (High; H) and once during 10 min at 24,000 ft, followed by 30 min at 15,000 ft and by 80 min at 24,000 ft (high–low–high; H–L–H). VGE scores were assessed by cardiac ultrasound, using a 6-graded scale. In H, VGE increased throughout the course of the sojourn at 24,000 ft to attain peak value [median (range)] of 3 (2–4) at min 90, just prior to descent. In H–L–H, median VGE scores were 0 throughout the trial, except for at min 10, just prior to the excursion to 15,000 ft, whence the VGE score was 1.5 (0–3). Thus, an early, single excursion from high to moderate cabin altitude holds promise as an in-flight means to reduce the risk of altitude decompression sickness during long-duration high-altitude flying in aircraft with limited cabin pressurization. Presumably, such excursion acts by facilitating the gas exchange in decompression bubbles from a predomination of nitrogen to that of oxygen.

Hyperoxic Effects on Decompression Strain During Alternating High and Moderate Altitude Exposures.

INTRODUCTION: In fighter aircraft, long-duration high-altitude sorties are typically interrupted by refueling excursions to lower altitude. In normoxia, excursions to moderate cabin altitude may increase the occurrence of venous gas emboli (VGE) at high cabin altitude. The aim was to investigate the effect of hyperoxia on VGE and decompression sickness (DCS) during alternating high and moderate altitude exposure.METHODS: In an altitude chamber, 13 healthy men were exposed to three different conditions: A) 90 min at 24,000 ft (7315 m) breathing normoxic gas (54% O₂; H-NOR); B) 90 min at 24,000 ft breathing hyperoxic gas (90% O₂; H-HYP); and C) three 30-min exposures to 24,000 ft interspersed by two 30-min exposures to 18,000 ft (5486 m) breathing 90% O₂ (ALT-HYP). VGE occurrence was evaluated from cardiac ultrasound imaging. DCS symptoms were rated using a scale.RESULTS: DCS occurred in all conditions and altogether in 6 of the 39 exposures. The prevalence of VGE was similar in H-NOR and H-HYP throughout the exposures. During the initial 30 min at 24,000 ft, the prevalence of VGE was similar in ALT-HYP as in the other two conditions, whereas, after the first excursion to 18,000 ft, the VGE score was lower in ALT-HYP than in H-NOR and H-HYP.DISCUSSION: Hyperoxic excursions from 24,000 to 18,000 ft reduces VGE occurrence, presumably by facilitating diffusive gas exchange across the bubble surfaces, increasing the share of bubble content contributed by oxygen. Still, the excursions did not abolish the DCS risk.Ånell R, Grönkvist M, Gennser M, Eiken O. Hyperoxic effects on decompression strain during alternating high and moderate altitude exposures. Aerosp Med Hum Perform. 2021; 92(4):223230.

Venous cerebral blood volume mapping in the whole brain using venous-spin-labeled 3D turbo spin echo.

Venous cerebral blood volume (CBVv ) is a major contributor to BOLD contrast, and therefore is an important parameter for understanding the underlying mechanism. Here, we propose a velocity-selective venous spin labeling (VS-VSL)-prepared 3D turbo spin echo pulse sequence for whole-brain baseline CBVv mapping. Unlike previous CBVv measurement techniques that exploit the interrelationship between BOLD signals and CBVv , in the proposed VS-VSL technique both arterial blood and cerebrospinal fluid (CSF) signals were suppressed before the VS pulse train for exclusive labeling of venous blood, while a single-slab 3D turbo spin echo readout was used because of its relative immunity to magnetic field variations. Furthermore, two approximations were made to the VS-VSL signal model for simplified derivation of CBVv . In vivo studies were performed at 3T field strength in 8 healthy subjects. The performance of the proposed VS-VSL method in baseline CBVv estimation was first evaluated in comparison to the existing, hyperoxia-based method. Then, data were also acquired using VS-VSL under hypercapnic and hyperoxic gas breathing challenges for further validation of the technique. The proposed technique yielded physiologically plausible baseline CBVv values, and when compared with the hyperoxia-based method, showed no statistical difference. Furthermore, data acquired using VS-VSL yielded average CBVv of 2.89%/1.78%, 3.71%/2.29%, and 2.88%/1.76% for baseline, hypercapnia, and hyperoxia, respectively, in gray/white matter regions. As expected, hyperoxia had negligible effect (P >.8), whereas hypercapnia demonstrated vasodilation (P<<.01). Upon further validation of the quantification model, the method is expected to have merit for 3D CBVv measurements across the entire brain.

Cardiopulmonary function during supramaximal exercise in hypoxia, normoxia and hyperoxia in Thoroughbred horses.

ABSTRACTSupramaximal exercise while inspiring different O2 gases may induce different responses in cardiopulmonary function at the same relative and/or absolute exercise intensity. The purpose of this study was to compare the effects of supramaximal exercise in hypoxia, normoxia and hyperoxia on cardiopulmonary function in Thoroughbred horses. Using a crossover design, five well-trained horses were made to run up a 6% grade on a treadmill at supramaximal speeds sustainable for approximately 110 sec (approximately 115% V̇O2max) while breathing normoxic gas (NO, 21% O2) or hypoxic gas (LO, 15.3% O2) in random order. Horses also ran at the same speed, incline and run time as in NO while breathing hyperoxic gas (HONO, 28.8% O2) and as in LO while breathing normoxic gas (NOLO). Runs were on different days, and cardiopulmonary variables were analyzed with repeated-measures ANOVA and the Holm-Šidák method for pairwise comparisons. Supramaximal speeds differed significantly between NO and LO (14.0 ± 0.5 [SD] m/sec vs. 12.6 ± 0.5 m/sec), but run times to exhaustion did not (112 ± 17 sec vs. 103 ± 14 sec). The V̇O2max in NO was higher than that in LO (165 ± 11 vs. 120 ± 15 ml (min× kg)), as was the arterial oxygen tension (66 ± 5 vs. 45 ± 2 Torr). Oxygen consumption was increased in HONO and NOLO compared with the values in NO and LO, respectively. Supramaximal exercise in hypoxia induces more severe hypoxemia and decreases V̇O2max compared with normoxia at the same relative intensity. Conversely, supramaximal exercise in hyperoxia alleviates hypoxemia and increases V̇O2 compared with normoxia at the same absolute intensity.

Hyperoxia enhances self-paced exercise performance to a greater extent in cool than hot conditions.

What is the central question of this study? Hyperoxia enhances endurance performance by increasing O2 availability to locomotor muscles. We investigated whether hyperoxia can also improve prolonged self-paced exercise in conditions of elevated thermal and cardiovascular strain. What is the main finding and its importance? Hyperoxia improved self-paced exercise performance in hot and cool conditions. However, the extent of the improvement (increased work rate relative to normoxia) was greater in cool conditions. This suggests that the development of thermal and cardiovascular strain during prolonged self-paced exercise under heat stress might attenuate the hyperoxia-mediated increase in O2 delivery to locomotor muscles. The aim of this study was to determine whether breathing hyperoxic gas when self-paced exercise performance is impaired under heat stress enhances power output. Nine well-trained male cyclists performed four 40min cycling time trials: two at 18°C (COOL) and two at 35°C (HOT). For the first 30min, participants breathed ambient air, and for the remaining 10min normoxic (fraction of inspired O2 0.21; NOR) or hyperoxic (fraction of inspired O2 0.45; HYPER) air. During the first 30min of the time trials, power output was lower in the HOT (∼250W) compared with COOL (∼273W) conditions (P<0.05). In the final 10min, power output was higher in HOT-HYPER (264±25W) than in HOT-NOR (244±31W; P=0.008) and in COOL-HYPER (315±28W) than in COOL-NOR (284±25W; P<0.001). The increase in absolute power output in COOL-HYPER was greater than in HOT-HYPER (∼12W; P=0.057), as was normalized power output (∼30%; P<0.001). The peripheral capillary percentage oxygen saturation increased in HOT-HYPER and COOL-HYPER (P<0.05), with COOL-HYPER being higher than HOT-HYPER (P<0.01). Heart rate was higher during the HOT compared with COOL trials (P<0.01), as were mean skin temperature (P<0.001) and peak rectal temperature (HOT, ∼39.5°C and COOL, ∼38.9°C; P<0.01). Thermal discomfort was also higher in the HOT compared with COOL (P<0.01), whereas ratings of perceived exertion were similar (P>0.05). Hyperoxia enhanced performance during the final 25% of a 40min time trial in both HOT and COOL conditions compared with normoxia. However, the attenuated increase in absolute and normalized power output noted in the HOT condition suggests that heat stress might mitigate the influence of hyperoxia.

The effects of hyperoxia on repeated sprint cycling performance & muscle fatigue

ObjectivesHyperoxia (>21% oxygen) can evoke performance improvements in aerobic and anaerobic exercise. The aims of the current study were to determine the effects of breathing hyperoxic gas (fraction of inspired oxygen [FiO2] 1.00) on repeated cycle performance, and to assess the nature and extent of fatigue after intermittent sprinting. Design & methodsTesting (n=14 males) comprised two visits to the laboratory. Each session involved 10×15s repeated cycle sprints breathing FiO2 1.00 (hyperoxia) or FiO2 0.21 (normoxia). Muscle fatigue was measured pre and post sprints using Maximal Voluntary Contraction (MVC), voluntary activation (VA) and potentiated doublet twitch (PTF). Blood lactate (BLa) was taken between sprints.Paired samples t-tests were used to examine difference between conditions in power output (peak and mean Watts) and BLa. Two-way ANOVA was used to examine fatigue variables pre and post sprints according to condition. ResultsMean power output was 4% greater in hyperoxia (p<0.01), with no difference in peak power (p>0.05). There was a significant increase in BLa in hyperoxia compared with normoxia (p<0.01) in sprints 4 and 8, as well as meaningful difference in sprints 4–10. There was no significant difference in fatigue factors (MVC, VA and PTF) (p>0.05) in response to the cycling, although a large drop in PTF occurred in both conditions. ConclusionHyperoxia can elicit improvements in mean cycling power, with no significant change in post exercise muscle fatigue. Hyperoxia as a training aid may provide performance enhancing effects during repeated sprint cycling by reducing concurrent muscle fatigue, primarily via peripheral factors.

Oxygen‐sensitive MRI assessment of tumor response to hypoxic gas breathing challenge

Oxygen-sensitive MRI has been extensively used to investigate tumor oxygenation based on the response (R2 * and/or R1 ) to a gas breathing challenge. Most studies have reported response to hyperoxic gas indicating potential biomarkers of hypoxia. Few studies have examined hypoxic gas breathing and we have now evaluated acute dynamic changes in rat breast tumors. Rats bearing syngeneic subcutaneous (n=15) or orthotopic (n=7) 13762NF breast tumors were exposed to a 16% O2 gas breathing challenge and monitored using blood oxygen level dependent (BOLD) R2 *and tissue oxygen level dependent (TOLD) T1 -weighted measurements at 4.7T. As a control, we used a traditional hyperoxic gas breathing challenge with 100% O2 on a subset of the subcutaneous tumor bearing rats (n=6). Tumor subregions identified as responsive on the basis of R2 * dynamics coincided with the viable tumor area as judged by subsequent H&E staining. As expected, R2 * decreased and T1 -weighted signal increased in response to 100% O2 breathing challenge. Meanwhile, 16% O2 breathing elicited an increase in R2 *, but divergent response (increase or decrease) in T1 -weighted signal. The T1 -weighted signal increase may signify a dominating BOLD effect triggered by 16% O2 in the relatively more hypoxic tumors, whereby the influence of increased paramagnetic deoxyhemoglobin outweighs decreased pO2 . The results emphasize the importance of combined BOLD and TOLD measurements for the correct interpretation of tumor oxygenation properties.

High adventure shunts old notions of pulmonary vascular control during hypoxic exercise: contrasting views that might just burst your bubble!

High adventure shunts old notions of pulmonary vascular control during hypoxic exercise: contrasting views that might just burst your bubble!

Case Studies in Physiology: The Case of the Giant Giraffe.

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Intrapulmonary arteriovenous anastomoses in humans with chronic obstructive pulmonary disease: implications for cryptogenic stroke?

What is the central question of this study? Do individuals with chronic obstructive pulmonary disease have blood flow through intrapulmonary arteriovenous anastomoses at rest or during exercise? What is the main finding and its importance? Individuals with chronic obstructive pulmonary disease have a greater prevalence of blood flow through intrapulmonary arteriovenous anastomoses at rest than age-matched control subjects. Given that the intrapulmonary arteriovenous anastomoses are large enough to permit venous emboli to pass into the arterial circulation, patients with chronic obstructive pulmonary disease and an elevated risk of thrombus formation may be at risk of intrapulmonary arteriovenous anastomosis-facilitated embolic injury (e.g. stroke or transient ischaemic attack). The pulmonary capillaries prevent stroke by filtering venous emboli from the circulation. Intrapulmonary arteriovenous anastomoses are large-diameter (≥50μm) vascular connections in the lung that may compromise the integrity of the pulmonary capillary filter and have recently been linked to cryptogenic stroke and transient ischaemic attack. Prothrombotic populations, such as individuals with chronic obstructive pulmonary disease (COPD), may be at increased risk of stroke and transient ischaemic attack facilitated by intrapulmonary arteriovenous anastomoses, but the prevalence and degree of blood flow through intrapulmonary arteriovenous anastomoses in this population has not been fully examined and compared with age-matched healthy control subjects. We used saline contrast echocardiography to assess blood flow through intrapulmonary arteriovenous anastomoses at rest (n=29 COPD and 19 control subjects) and during exercise (n=10 COPD and 10 control subjects) in subjects with COPD and age-matched healthy control subjects. Blood flow through intrapulmonary arteriovenous anastomoses was detected in 23% of subjects with COPD at rest and was significantly higher compared with age-matched healthy control subjects. Blood flow through intrapulmonary arteriovenous anastomoses at rest was reduced or eliminated in subjects with COPD after breathing hyperoxic gas. Sixty per cent of subjects with COPD who did not have blood flow through the intrapulmonary arteriovenous anastomoses at rest had blood flow through them during exercise. The combination of blood flow through intrapulmonary arteriovenous anastomoses and potential for thrombus formation in individuals with COPD may permit venous emboli to pass into the arterial circulation and cause stroke and transient ischaemic attack. Breathing supplemental oxygen may reduce this risk in COPD. The link between blood flow through intrapulmonary arteriovenous anastomoses, stroke and transient ischaemic attack is worthy of future investigation in COPD and other populations.

Impact of Dietary Tomato Juice on Changes in Pulmonary Oxidative Stress, Inflammation and Structure Induced by Neonatal Hyperoxia in Mice (Mus musculus).

Many preterm infants require hyperoxic gas for survival, although it can contribute to lung injury. Experimentally, neonatal hyperoxia leads to persistent alterations in lung structure and increases leukocytes in bronchoalveolar lavage fluid (BALF). These effects of hyperoxia on the lungs are considered to be caused, at least in part, by increased oxidative stress. Our objective was to determine if dietary supplementation with a known source of antioxidants (tomato juice, TJ) could protect the developing lung from injury caused by breathing hyperoxic gas. Neonatal mice (C57BL6/J) breathed either 65% O2 (hyperoxia) or room air from birth until postnatal day 7 (P7d); some underwent necropsy at P7d and others were raised in room air until adulthood (P56d). In subsets of both groups, drinking water was replaced with TJ (diluted 50:50 in water) from late gestation to necropsy. At P7d and P56d, we analyzed total antioxidant capacity (TAC), markers of oxidative stress (nitrotyrosine and heme oxygenase-1 expression), inflammation (interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) expression), collagen (COL) and smooth muscle in the lungs; we also assessed lung structure. We quantified macrophages in lung tissue (at P7d) and leukocytes in BALF (at P56d). At P7d, TJ increased pulmonary TAC and COL1α1 expression and attenuated the hyperoxia-induced increase in nitrotyrosine and macrophage influx; however, changes in lung structure were not affected. At P56d, TJ increased TAC, decreased oxidative stress and reversed the hyperoxia-induced increase in bronchiolar smooth muscle. Additionally, TJ alone decreased IL-1β expression, but following hyperoxia TJ increased TNF-α expression and did not alter the hyperoxia-induced increase in leukocyte number. We conclude that TJ supplementation during and after neonatal exposure to hyperoxia protects the lung from some but not all aspects of hyperoxia-induced injury, but may also have adverse side-effects. The effects of TJ are likely due to elevation of circulating antioxidant concentrations.

Does Hyperoxia Alter the Mechanoreflex in Young Healthy Males and Females?

Passive limb movement (PLM) has been used as a method of activating the mechanoreflex, inducing limb hyperemia which is nitric oxide (NO) dependent. Breathing hyperoxic gas has been used as a model to elevate free radicals (FR), though it remains to be seen, in humans, if acute elevations in FR alter the mechanoreflex response to PLM, and whether the effect may be sex specific. PURPOSE: The purpose of this study was to compare the male and female central and peripheral hemodynamic responses to dynamic PLM, under normoxic (21% O2) and hyperoxic (100% O2) conditions. METHODS: In 23 young healthy participants (12 female(F) and 11 male(M)) using a single blind design, participants were positioned supine and breathed normoxic (21% O2) and hyperoxic (100% O2) gas from a Douglas bag for 10 minutes, after which 2 minutes of PLM were performed. Central hemodynamic responses (cardiac output [CO], stroke volume [SV], and HR), were measured using a Finometer, while a near-infrared spectrometer (NIRS) was used to assess the microvascular response (tissue oxygen saturation, StO2%) at baseline and during the PLM. RESULTS: No sex differences in hemodynamics were observed at baseline in normoxia (p>0.05). In response to PLM, both sexes increased HR and CO from baseline (p<0.05); however, males elicited significantly higher CO response than females (ΔCO: 1.7±0.7 vs. 0.9±0.6 L/min, p<0.05). Peripherally, PLM increased StO2 from baseline for both sexes (p<0.05), though there was a significant difference in the peripheral response to PLM between the sexes (M: 4.2±2.0 vs F: 2.3±2.7 ΔStO2%, p<0.05). Hyperoxia had no effect on baseline CO or StO2 (p>0.05) or the response to PLM, and the sex difference persisted (ΔCO: 1.8 ± 1.0 vs 1.1 ± 0.6 L/min, M v. F) (p<0.05). PLM induced significant changes in StO2, which were not different from normoxia, though the sex specificity persisted (M: 4.5±1.8 vs F: 2.1±2.7 ΔStO2%, p<0.05). CONCLUSION: The present study provides further evidence that females exhibit an attenuated mechanoreflex as compared to males, which may reduce CVD risk. Though, unlike the macrovascular responses to PLM which have been reported to be similar between sexes, the microvascular responses to PLM may differ. In the current model, prior inhalation of 100% oxygen had no effect on the mechanoreflex in in young healthy males and females.

Measuring Uptake and Elimination of Nitrogen in Humans at Different Ambient Pressures

To measure nitrogen (N2) wash-out and uptake requires elaborate set-ups, especially when doing the measurements at increased or decreased ambient pressure. Here we present a transportable device for quantifying N2 turnover in humans which can be used at different ambient pressures. A modified close-circuit electronic rebreather was used to assess N2 turnover. Changes in N2 volume within the rebreathing circuit, reflecting N2 uptake or washout, were derived from the continuously monitored total system volume and the calculated volumes of oxygen and water vapor. The calculation of continuous N2 volume curves was performed off-line using dedicated computer software. Four subjects participated in the proof-of-concept tests. At steady state, the drift in calculated N2 volume in the rebreathing circuit over a 1-h duration was minimal. Three of the subjects participated in additional N2 steady-state measurements where 1019 mL (BTPD) of N2 was injected into the rebreathing circuit over 20 min and the measured volume increase was 1006 ± 32 mL. Lastly, N2 elimination was assessed during decompression to 0.5 atm and while breathing hyperoxic gas. N2 uptake was measured during compression to 1.8 atm. The elimination and uptake curves were deemed to be realistic. A method for assessing N2 turnover in humans has been developed and a first evaluation has been performed. It is easy to work with operationally and can be used at different ambient pressures. More research is needed in order to further validate it as a method for assessing N2 turnover in humans.Sundblad P, Frånberg O, Siebenmann C, Gennser M. Measuring uptake and elimination of nitrogen in humans at different ambient pressures. Aerosp Med Hum Perform. 2016; 87(12):1045-1050.

Pulseless Oximetry: A Preliminary Evaluation

Pulse oximetry fails when pulsations are weak or absent, common in patients with continuous flow left ventricular assist devices (LVADs). We developed a method to measure arterial oxygenation (Sao2) noninvasively in pulseless patients with LVADs. The technique involves 5- to 10-s occlusions of radial and ulnar arteries on one hand. A fingertip is transilluminated alternately with light-emitting diodes emitting 660 nm (red) and 905 nm (infrared). During the approximately 1 s after release of occlusion, changing attenuance of each wavelength is measured and their red/infrared arterial blood attenuance ratio (R/IR) calculated. We studied five normal subjects breathing hyperoxic, normoxic, or hypoxic gas mixtures to establish a calibration curve, using standard pulse oximetry as the gold standard. We also studied seven pulseless patients with LVADs (two studied twice) at clinically determined oxygenation. Normal subject data showed close correlation of oxygen saturation by pulse oximetry (Spo2) with R/IR, (Spo2 = 111 - [26.7 × R/IR]; R2 = 0.975). For patients with LVADs, predicted Sao2 (from the calibration curve) tended to underestimate measured Sao2 (from arterial blood) by a clinically insignificant 1.1 ± 1.6 percentage points (mean ± SD), maximum 3.4 percentage points. Preliminary results in a small number of patients demonstrate that pulseless oximetry can be used to estimate arterial saturation with acceptable accuracy. A noninvasive oximeter that does not rely on pulsatile flow would be a valuable advance in assessing oxygenation in patients with LVADs, for whom the only current option is arterial puncture, which is painful, risks arterial injury, and only provides a snapshot evaluation of oxygenation.

Dynamic oxygen challenge evaluated by NMR T1 and T2*--insights into tumor oxygenation.

There is intense interest in developing non-invasive prognostic biomarkers of tumor response to therapy, particularly with regard to hypoxia. It has been suggested that oxygen sensitive MRI, notably blood oxygen level-dependent (BOLD) and tissue oxygen level-dependent (TOLD) contrast, may provide relevant measurements. This study examined the feasibility of interleaved T2*- and T1-weighted oxygen sensitive MRI, as well as R2* and R1 maps, of rat tumors to assess the relative sensitivity to changes in oxygenation. Investigations used cohorts of Dunning prostate R3327-AT1 and R3327-HI tumors, which are reported to exhibit distinct size-dependent levels of hypoxia and response to hyperoxic gas breathing. Proton MRI R1 and R2* maps were obtained for tumors of anesthetized rats (isoflurane/air) at 4.7 T. Then, interleaved gradient echo T2*- and T1-weighted images were acquired during air breathing and a 10 min challenge with carbogen (95% O2 -5% CO2). Signals were stable during air breathing, and each type of tumor showed a distinct signal response to carbogen. T2* (BOLD) response preceded T1 (TOLD) responses, as expected. Smaller HI tumors (reported to be well oxygenated) showed the largest BOLD and TOLD responses. Larger AT1 tumors (reported to be hypoxic and resist modulation by gas breathing) showed the smallest response. There was a strong correlation between BOLD and TOLD signal responses, but ΔR2* and ΔR1 were only correlated for the HI tumors. The magnitude of BOLD and TOLD signal responses to carbogen breathing reflected expected hypoxic fractions and oxygen dynamics, suggesting potential value of this test as a prognostic biomarker of tumor hypoxia.

Abstract 13728: Changes in Myocardial Function Following 8 to 12-hour Rebreathing Cold Water Dives

Aim: This study assessed hemodynamic changes and myocardial function after prolonged dynamic cold water immersions with hyperbaric hyperoxic exposure. Methods: Trained military divers were studied during 8-hour (6 subjects) and 12-hour (6 subjects) dives in a hyperbaric chamber (1.7 and 3 bar) in 18°C water. Subjects were breathing hyperoxic gas (100% oxygen or up to 1.7 bar PO2) and performed bouts of physical exercise. Conventional and speckle tracking transthoracic echocardiography (TTE) were performed before, immediately after, and 15 hours after dives. Results: We observed a decrease in left and right ventricular preloads, and lowered stroke volume immediately after dives. These parameters remained below baseline values 15h after dive termination. These changes were not significantly different between 8h and 12h dives. Speckle tracking analysis showed altered function of the left and right ventricles reflected by a transient decrease in ventricular parameters as measured by echography in the hour immediately after the end of immersion (table). Conclusion: Hemodynamic changes and transient alterations in strain and strain rate myocardial parameters were assessed immediately after 8 to 12 h dives. Immersion-linked changes in blood volume were likely involved in lowering cardiac preload and stroke volume. Altered ventricular strain and strain rates could be the result of lowered blood volume, hyperoxic breathing and increased cardiac pre- and after-load.

Reversal of hypoxia in murine atherosclerosis prevents necrotic core expansion by enhancing efferocytosis.

Advanced murine and human plaques are hypoxic, but it remains unclear whether plaque hypoxia is causally related to atherogenesis. Here, we test the hypothesis that reversal of hypoxia in atherosclerotic plaques by breathing hyperoxic carbogen gas will prevent atherosclerosis. Low-density lipoprotein receptor-deficient mice (LDLR(-/-)) were fed a Western-type diet, exposed to carbogen (95% O2, 5% CO2) or air, and the effect on plaque hypoxia, size, and phenotype was studied. First, the hypoxic marker pimonidazole was detected in murine LDLR(-/-) plaque macrophages from plaque initiation onwards. Second, the efficacy of breathing carbogen (90 minutes, single exposure) was studied. Compared with air, carbogen increased arterial blood pO2 5-fold in LDLR(-/-) mice and reduced plaque hypoxia in advanced plaques of the aortic root (-32%) and arch (-84%). Finally, the effect of repeated carbogen exposure on progression of atherosclerosis was studied in LDLR(-/-) mice fed a Western-type diet for an initial 4 weeks, followed by 4 weeks of diet and carbogen or air (both 90 min/d). Carbogen reduced plaque hypoxia (-40%), necrotic core size (-37%), and TUNEL(+) (terminal uridine nick-end labeling positive) apoptotic cell content (-50%) and increased efferocytosis of apoptotic cells by cluster of differentiation 107b(+) (CD107b, MAC3) macrophages (+36%) in advanced plaques of the aortic root. Plaque size, plasma cholesterol, hematopoiesis, and systemic inflammation were unchanged. In vitro, hypoxia hampered efferocytosis by bone marrow-derived macrophages, which was dependent on the receptor Mer tyrosine kinase. Carbogen restored murine plaque oxygenation and prevented necrotic core expansion by enhancing efferocytosis, likely via Mer tyrosine kinase. Thus, plaque hypoxia is causally related to necrotic core expansion.

Correlations of noninvasive BOLD and TOLD MRI with pO2 and relevance to tumor radiation response

To examine the potential use of blood oxygenation level dependent (BOLD) and tissue oxygenation level dependent (TOLD) contrast MRI to assess tumor oxygenation and predict radiation response. BOLD and TOLD MRI were performed on Dunning R3327-AT1 rat prostate tumors during hyperoxic gas breathing challenge at 4.7 T. Animals were divided into two groups. In Group 1 (n = 9), subsequent (19) F MRI based on spin lattice relaxation of hexafluorobenzene reporter molecule provided quantitative oximetry for comparison. For Group 2 rats (n = 13) growth delay following a single dose of 30 Gy was compared with preirradiation BOLD and TOLD assessments. Oxygen (100%O2 ) and carbogen (95%O2 /5%CO2 ) challenge elicited similar BOLD, TOLD and pO2 responses. Strong correlations were observed between BOLD or R2* response and quantitative (19) F pO2 measurements. TOLD response showed a general trend with weaker correlation. Irradiation caused a significant tumor growth delay and tumors with larger changes in TOLD and R1 values upon oxygen breathing exhibited significantly increased tumor growth delay. These results provide further insight into the relationships between oxygen sensitive (BOLD/TOLD) MRI and tumor pO2 . Moreover, a larger increase in R1 response to hyperoxic gas challenge coincided with greater tumor growth delay following irradiation.