Nocturnal pulse oximetry for the detection and prediction of acute mountain sickness: An observational study.

Acute mountain sickness (AMS) is a well-studied illness defined by clinical features (e.g., headache and nausea), as assessed by the Lake Louise score (LLS). Although obvious in its severe form, early stages of AMS are poorly defined and easily confused with common travel-related conditions. Measurement of hypoxaemia, the cause of AMS, should be helpful, yet to date its utility for identifying AMS susceptibility remains unclear. This study quantified altitude-induced hypoxaemia in individuals during an ascent to 4800 m to determine the utility of nocturnal pulse oximetry measurements for prediction of AMS. Eighteen individuals (36 ± 16 years of age) ascended to 4800 m over 12 days. Symptomology of AMS was assessed each morning via LLS criteria, with participants categorized as either AMS-positive (LLS ≥ 3 with headache) or AMS-negative. Overnight peripheral oxygen saturations (ov- S p O 2 ${{S}_{{\mathrm{p}}{{{\mathrm{O}}}_2}}}$ ) were recorded continuously (1 Hz) using portable oximeters. Derivatives of these recordings were compared between AMS-positive and -negative subjects (Mann-Whitney U-test). Exploratory analyses (Pearson's) were conducted to investigate relationships between overnight parameters and AMS severity. Overnight derivatives, including ov- S p O 2 ${{S}_{{\mathrm{p}}{{{\mathrm{O}}}_2}}}$ , heart rate/ov- S p O 2 ${{S}_{{\mathrm{p}}{{{\mathrm{O}}}_2}}}$ , variance, oxygen desaturation index, hypoxic burden and total sleep time at <80% S p O 2 ${{S}_{{\mathrm{p}}{{{\mathrm{O}}}_2}}}$ , all differed significantly between AMS-positive and -negative subjects (all P < 0.01), with cumulative/relative frequency plots highlighting these differences visually. Exploratory analysis revealed that ov- S p O 2 ${{S}_{{\mathrm{p}}{{{\mathrm{O}}}_2}}}$ from 3850 m was correlated with peak LLS at 4800 m (r = 0.58-0.61). The findings highlight the potential for overnight oximetry to predict AMS susceptibility during ascent to high altitude. Further investigation is required to develop, evaluate and optimize predictive models to improve AMS management and prevention.

Pulse oximetry for the prediction of acute mountain sickness: A systematic review.

Acute mountain sickness (AMS) causes serious illness for many individuals ascending to high altitude (HA), although preventable with appropriate acclimatisation. AMS is a clinical diagnosis, with symptom severity evaluated using the Lake Louise Score (LLS). Reliable methods of predicting which individuals will develop AMS have not been developed. This systematic review evaluates whether a predictive relationship exists between oxygen saturation and subsequent development of AMS. PubMed, PubMed Central, MEDLINE, Semantic Scholar, Cochrane Library, University of Birmingham Library and clinicaltrials.gov databases were systematically searched from inception to 15 June 2023. Human studies involving collection of peripheral blood oxygen saturation ( S p O 2 ${{S}_{{\mathrm{p}}{{{\mathrm{O}}}_{\mathrm{2}}}}}$ ) from healthy lowlanders during ascent to HA that evaluated any relationship between S p O 2 ${{S}_{{\mathrm{p}}{{{\mathrm{O}}}_{\mathrm{2}}}}}$ and AMS severity were considered for eligibility. Risk of bias was assessed using a modified Newcastle-Ottawa Tool for cohort studies (PROPSPERO CRD42023423542). Seven of 980 total identified studies were ultimately included for data extraction. These studies evaluated S p O 2 ${{S}_{{\mathrm{p}}{{{\mathrm{O}}}_{\mathrm{2}}}}}$ and AMS (via LLS) in 1406 individuals during ascent to HA (3952-6300 m). Risk of bias was 'low' for six and 'moderate' for one of the included studies. Ascent profiles and S p O 2 ${{S}_{{\mathrm{p}}{{{\mathrm{O}}}_{\mathrm{2}}}}}$ measurement methodology varied widely, as did the statistical methods for AMS prediction. Decreasing oxygen saturation measured with pulse oximetry during ascent shows a positive predictive relationship for individuals who develop AMS. Studies have high heterogeneity in ascent profile and oximetry measurement protocols. Further studies with homogeneous methodology are required to enable statistical analysis for more definitive evaluation of AMS predictability by pulse oximetry.

Anthocyanin-Rich Blackcurrant Extract Preserves Gastrointestinal Barrier Permeability and Reduces Enterocyte Damage but Has No Effect on Microbial Translocation and Inflammation After Exertional Heat Stress.

This study investigated the effects of 7 days of 600 mg/day anthocyanin-rich blackcurrant extract intake on small intestinal permeability, enterocyte damage, microbial translocation, and inflammation following exertional heat stress. Twelve recreationally active men (maximal aerobic capacity = 55.6 ± 6.0 ml·kg-1·min-1) ran (70% VO2max) for 60 min in an environmental chamber (34 °C, 40% relative humidity) on two occasions (placebo/blackcurrant, randomized double-blind crossover). Permeability was assessed from a 4-hr urinary excretion of lactulose and rhamnose and expressed as a ratio of lactulose/rhamnose. Venous blood samples were taken at rest and 20, 60, and 240 min after exercise to measure enterocyte damage (intestinal fatty acid-binding protein); microbial translocation (soluble CD14, lipopolysaccharide-binding protein); and interleukins 6, interleukins 10, and interleukins 1 receptor antagonist. Exercise increased rectal temperature (by ∼2.8 °C) and heart rate (by ∼123 beats/min) in each condition. Blackcurrant supplementation led to a ∼12% reduction in lactulose/rhamnose ratio (p < .0034) and enterocyte damage (∼40% reduction in intestinal fatty acid-binding protein area under the curve; p < .0001) relative to placebo. No between-condition differences were observed immediately after exercise for lipopolysaccharide-binding protein (mean, 95% confidence interval [CI]; +80%, 95% CI [+61%, +99%]); soluble CD14 (+37%, 95% CI [+22%, +51%]); interleukins 6 (+494%, 95% CI [+394%, +690%]); interleukins 10 (+288%, 95% CI [+105%, +470%]); or interleukins 1 receptor antagonist (+47%, 95% CI [+13%, +80%]; all time main effects). No between-condition differences for these markers were observed after 60 or 240 min of recovery. Blackcurrant extract preserves the GI barrier; however, at subclinical levels, this had no effect on microbial translocation and downstream inflammatory processes.

Effect of losartan on performance and physiological responses to exercise at high altitude (5035 m).

OBJECTIVE: Altitude-related and exercise-related elevations in blood pressure (BP) increase the likelihood of developing pulmonary hypertension and high-altitude illness during high-altitude sojourn. This study examined the antihypertensive effect and potential exercise benefit of the angiotensin II receptor antagonist losartan when taken at altitude. METHODS: Twenty participants, paired for age and ACE genotype status, completed a double-blinded, randomised study, where participants took either losartan (100 mg/day) or placebo for 21 days prior to arrival at 5035 m (Whymper Hut, Mt Chimborazo, Ecuador). Participants completed a maximal exercise test on a supine cycle ergometer at sea level (4 weeks prior) and within 48 hours of arrival to 5035 m (10-day ascent). Power output, beat-to-beat BP, oxygen saturation (SpO2) and heart rate (HR) were recorded during exercise, with resting BP collected from daily medicals during ascent. Before and immediately following exercise at 5035 m, extravascular lung water prevalence was assessed with ultrasound (quantified via B-line count). RESULTS: At altitude, peak power was reduced relative to sea level (p<0.01) in both groups (losartan vs placebo: down 100±29 vs 91±28 W, p=0.55), while SpO2 (70±6 vs 70±5%, p=0.96) and HR (146±21 vs 149±24 bpm, p=0.78) were similar between groups at peak power, as was the increase in systolic BP from rest to peak power (up 80±37 vs 69±33 mm Hg, p=0.56). Exercise increased B-line count (p<0.05), but not differently between groups (up 5±5 vs 8±10, p=0.44). CONCLUSION: Losartan had no observable effect on resting or exercising BP, exercise-induced symptomology of pulmonary hypertension or performance at 5035 m.

Hypoxia is not the primary mechanism contributing to exercise-induced proteinuria.

INTRODUCTION: Proteinuria increases at altitude and with exercise, potentially as a result of hypoxia. Using urinary alpha-1 acid glycoprotein (α1-AGP) levels as a sensitive marker of proteinuria, we examined the impact of relative hypoxia due to high altitude and blood pressure-lowering medication on post-exercise proteinuria. METHODS: Twenty individuals were pair-matched for sex, age and ACE genotype. They completed maximal exercise tests once at sea level and twice at altitude (5035 m). Losartan (100 mg/day; angiotensin-receptor blocker) and placebo were randomly assigned within each pair 21 days before ascent. The first altitude exercise test was completed within 24-48 hours of arrival (each pair within ~1 hour). Acetazolamide (125 mg two times per day) was administrated immediately after this test for 48 hours until the second altitude exercise test. RESULTS: With placebo, post-exercise α1-AGP levels were similar at sea level and altitude. Odds ratio (OR) for increased resting α1-AGP at altitude versus sea level was greater without losartan (2.16 times greater). At altitude, OR for reduced post-exercise α1-AGP (58% lower) was higher with losartan than placebo (2.25 times greater, p=0.059) despite similar pulse oximetry (SpO2) (p=0.95) between groups. Acetazolamide reduced post-exercise proteinuria by approximately threefold (9.3±9.7 vs 3.6±6.0 µg/min; p=0.025) although changes were not correlated (r=-0.10) with significant improvements in SpO2 (69.1%±4.5% vs 75.8%±3.8%; p=0.001). DISCUSSION: Profound systemic hypoxia imposed by altitude does not result in greater post-exercise proteinuria than sea level. Losartan and acetazolamide may attenuate post-exercise proteinuria, however further research is warranted.

Dietary supplementation with New Zealand blackcurrant extract enhances fat oxidation during submaximal exercise in the heat.

OBJECTIVES: This study investigated the effect of 7 days' supplementation with New Zealand blackcurrant extract on thermoregulation and substrate metabolism during running in the heat. DESIGN: Randomized, double-blind, cross-over study. METHODS: Twelve men and six women (mean±SD: Age 27±6 years, height 1.76±0.10m, mass 74±12kg, V̇O2max 53.4±7.0mLkg-1min-1) completed one assessment of maximal aerobic capacity and one familiarisation trial (18°C, 40% relative humidity, RH), before ingesting 2×300mgday-1 capsules of CurraNZ™ (each containing 105mg anthocyanin) or a visually matched placebo (2×300mg microcrystalline cellulose M102) for 7 days (washout 14 days). On day 7 of each supplementation period, participants completed 60min of fasted running at 65% V̇O2max in hot ambient conditions (34°C and 40% relative humidity). RESULTS: Carbohydrate oxidation was decreased in the NZBC trial [by 0.24gmin-1 (95% CI: 0.21-0.27gmin-1)] compared to placebo (p= 0.014, d=0.46), and fat oxidation was increased in the NZBC trial [by 0.12gmin-1 (95% CI: 0.10 to 0.15gmin-1)], compared to placebo (p=0.008, d=0.57). NZBC did not influence heart rate (p=0.963), rectal temperature (p=0.380), skin temperature (p=0.955), body temperature (p=0.214) or physiological strain index (p=0.705) during exercise. CONCLUSIONS: Seven-days intake of 600mg NZBC extract increased fat oxidation without influencing cardiorespiratory or thermoregulatory variables during prolonged moderate intensity running in hot conditions.

High-intensity intermittent exercise increases pulmonary interstitial edema at altitude but not at simulated altitude.

OBJECTIVE: Ascent to high altitude leads to a reduction in ambient pressure and a subsequent fall in available oxygen. The resulting hypoxia can lead to elevated pulmonary artery (PA) pressure, capillary stress, and an increase in interstitial fluid. This fluid can be assessed on lung ultrasound (LUS) by the presence of B-lines. We undertook a chamber and field study to assess the impact of high-intensity exercise in hypoxia on the development of pulmonary interstitial edema in healthy lowlanders. METHODS: Thirteen volunteers completed a high-intensity intermittent exercise (HIIE) test at sea level, in acute normobaric hypoxia (12% O2, approximately 4090 m equivalent altitude), and in hypobaric hypoxia during a field study at 4090 m after 6 days of acclimatization. Pulmonary interstitial edema was assessed by the evaluation of LUS B-lines. RESULTS: After HIIE, no increase in B-lines was seen in normoxia, and a small increase was seen in acute normobaric hypoxia (2 ± 2; P < .05). During the field study at 4090 m, 12 participants (92%) demonstrated 7 ± 4 B-lines at rest, which increased to 17 ± 5 immediately after the exercise test (P < .001). An increase was evident in all participants. There was a reciprocal fall in peripheral arterial oxygen saturations (Spo2) after exercise from 88% ± 4% to 80% ± 8% (P < .01). B-lines and Spo2 in all participants returned to baseline levels within 4 hours. CONCLUSIONS: HIIE led to an increase in B-lines at altitude after subacute exposure but not during acute exposure at equivalent simulated altitude. This may indicate pulmonary interstitial edema.

Exercise limitation of acetazolamide at altitude (3459 m).

OBJECTIVE: To assess the effect of acetazolamide (Az) on exercise performance during early acclimatization to altitude. METHODS: Az (250 mg twice daily) or placebo was administered for 3 days in a double-blind, randomized manner followed by a rapid ascent to 3459 m in the Italian Alps. Twenty healthy adults (age range, 18-67 years) were tested at 60% of sea-level peak power output for 15 minutes on a bicycle ergometer after 16 to 27 hours of altitude exposure. Exercise performance was measured in relation to peripheral oxygen saturations measured from pulse oximetry (Spo2), Lake Louise acute mountain sickness (AMS) score, and perceived difficulty. RESULTS: At altitude, resting Spo2 was higher in the Az group compared with placebo (P < .001). The highest AMS scores were in 4 of the placebo individuals with the lowest resting Spo2 (P < .05). During the exercise test, Spo2 fell in all but 1 subject (P < .001) and was reduced more in the Az group (P < .01). Four Az and 1 placebo subject were unable to complete the exercise test; 4 of these 5 had the largest fall in Spo2. The perception of exercise difficulty was higher in the Az subjects compared with those taking the placebo (P < .01). There was an age relationship with exercise limitation; 4 of the 9 older than 50 years failed to complete the test whereas only 1 of 11 younger than 50 years failed, and there were no failures in the 6 younger than 30 years (P < .05). CONCLUSIONS: In this study group, and despite higher resting Spo2, Az may have compromised exercise at 3459 m altitude during early acclimatization, particularly in older subjects.