Effect of Ultra-Marathon Trail Running at Sea Level and Altitude on Alveolar-Capillary Function and Lung Diffusion.

INTRODUCTION: Endurance exercise at altitude can increase cardiac output and pulmonary vascular pressure to levels that may exceed the stress-tolerability of the alveolar-capillary unit. This study examined the effect of ultra-marathon trail racing at different altitudes (ranging from <1000 m to between 1500 - 2700 m) on alveolar-capillary recruitment and lung diffusion. METHODS: Cardiac and lung function were examined before and after an ultra-marathon in 67 runners (age:41 ± 9y, BMI:23 ± 2 kg/m2, 10 females), and following 12-24 h of recovery in a subset (n = 27). Cardiac biomarkers (cTnI & BNP) were assessed from whole blood, while lung fluid accumulation (comet tails), stroke volume (SV) and cardiac output (Q) were quantified via echocardiography. Lung diffusing capacity for carbon monoxide (DLco) and its components, alveolar membrane conductance (Dm) and capillary blood volume (Vc), were determined via a single-breath method at rest and during three stages of submaximal semi-recumbent cycling (20, 30, & 40 W). RESULTS: Average race time was 25 ± 12 h. From pre- to post-race, there was an increase in cardiac biomarkers (cTnI: 0.04 ± .02 vs 0.13 ± .03 ng/ml; BNP: 20 ± 2 vs 112 ± 21 pg/ml, p < 0.01) and lung comet tails (2 ± 1 vs 7 ± 6, p < 0.01), a decrease in resting and exercise SV (76 ± 2 vs 69 ± 2 ml; 40 W: 93 ± 2 vs 88 ± 2 ml, p < 0.01), and an elevation in Q at rest (4.1 ± 0.1 vs 4.6 ± 0.2 l/min, p < 0.01; 40 W: 7.3 ± 0.2 vs 7.4 ± 0.3 l/min, p = 0.899). Resting DLco and Vc decreased after the race (p < 0.01), while Dm was unchanged (p = 0.465); however, during the three stages of exercise DLco, Vc and Dm were all reduced from pre- to post-race (40 W: 36.3 ± 0.9 vs 33.0 ± 0.8 mL/min/mmHg; 83 ± 3 vs 73 ± 2 mL; 186 ± 6 vs 170 ± 7 mL/min/mmHg, respectively, p < 0.01). When corrected for alveolar volume and Q, DLco decreased from pre- to post-race (p < 0.01), and changes in DLco were similar for all ultra-marathon events (p > 0.05). CONCLUSIONS: Competing in an ultra-marathon leads to a transient increase in cardiac injury biomarkers, mild lung-fluid accumulation, and impairments in lung diffusion. Reductions in DLco are predominantly caused by a reduced Vc and possible pulmonary capillary de-recruitment at rest. However, impairments in alveolar-capillary recruitment and Dm both contribute to a fall in exertional DLco following an ultra-marathon. Perturbations in lung diffusion were evident across a range of event distances and varying environmental exposures.

Lung "Comet Tails" in Healthy Individuals: Accumulation or Clearance of Extravascular Lung Water?

Parks, Jordan K, Courtney M. Wheatley-Guy, Glenn M. Stewart, Caitlin C. Fermoyle, Bryan J. Taylor, Jesse Schwartz, Briana Ziegler, Kay Johnson, Alice Gavet, Loïc Chabridon, Paul Robach, and Bruce D. Johnson. Lung "Comet Tails" in healthy individuals: accumulation or clearance of extravascular lung water? High Alt Med Biol. 24:230-233, 2023-Ultrasound lung comet tails (or B-lines) tend to be limited in number (<5) or absent under ultrasound examination, and the appearance of diffuse B-lines with lung sliding has been suggested to identify pulmonary edema. Clinical evaluation of B-lines has been utilized as a bedside test to assess pulmonary congestion in patients with heart failure. Exposure to altitude or prolonged exercise can alter fluid regulation and can lead to pulmonary congestion or edema. As such, B-lines have been utilized in the field to monitor for pathological lung fluid accumulation. However, ultrasound lung comet lines might not be as reliable for identifying extravascular lung water (EVLW) as previously thought in healthy individuals exercising at altitude where an increase in the number of ultrasound lung comets would reflect fluid buildup in the interstitial space of the alveoli and pulmonary capillaries. This report will focus on reviewing the literature and our data from a group of ultraendurance runners that completed the Ultra Trail Mont Blanc race that demonstrates that lung comet tails may not always be evidence of pathological fluid accumulation in healthy individuals and as such should be used to assess EVLW in concert with other diagnostic testing.

Semi-supervised exercise training program more effective for individuals with postural orthostatic tachycardia syndrome in randomized controlled trial.

PURPOSE: Exercise like any medication requires the correct dose; to be effective the appropriate frequency, duration, and intensity are necessary. This study aimed to assess if a semi-supervised exercise training (ET) program would be more effective at improving aerobic fitness (VO2PEAK), exercise tolerance, and symptoms in individuals with postural orthostatic tachycardia syndrome (POTS) compared to the standard of care (SOC). METHODS: Subjects were randomized to either the ET or SOC groups (n 26 vs. 23; age 33 ± 11 vs. 37 ± 10 years; VO2PEAK 66 ± 15 vs. 62 ± 15% predicted, ET vs. SOC respectively, p > 0.05). Composite Autonomic Symptom Score (COMPASS 31), 10 min stand test, and cardiopulmonary exercise test were performed at baseline and following 12 weeks. The ET group received an exercise consultation and eight semi-supervised in-person or virtual exercise sessions. RESULTS: The ET group demonstrated a greater improvement in VO2PEAK, higher or longer tolerance for baseline peak workload, and more often had a delayed symptom onset with exercise than the SOC group (ΔVO2PEAK 3.4 vs. - 0.2 mL/min/kg, p < 0.0001, ΔWorkload 19 ± 17 vs. 0 ± 10 W; Workload time 63 ± 29 vs. 22 ± 30 s; onset-delay 80% vs. 30%, p < 0.05). Individuals in the ET group reported a significant improvement in orthostatic intolerance domain score (p = 0.02), but there was not a significant difference in the improvement in total COMPASS score (- 11.38 vs. - 6.49, p = 0.09). CONCLUSION: Exercise training was more effective with greater improvements in aerobic fitness, orthostatic symptoms, and exercise tolerance for individuals with POTS when intensity and progression were personalized and delivered with minimal supervision compared to the SOC.

Sex-Specific Physiological Responses to Ultramarathon.

PURPOSE: Despite a growing body of literature on the physiological responses to ultramarathon, there is a paucity of data in females. This study assessed the female physiological response to ultramarathon and compared the frequency of perturbations to a group of race- and time-matched males. METHODS: Data were collected from 53 contestants of an ultramarathon trail race at the Ultra-Trail du Mont-Blanc (UTMB®) in 2018/19. Before and within 2 h of the finish, participants underwent physiological assessments, including blood sampling for biomarkers (creatine kinase-MB isoenzyme [CK-MB], cardiac troponin I [cTnI], brain natriuretic peptide [BNP], and creatinine [Cr]), pulmonary function testing (spirometry, exhaled NO, diffusing capacities, and mouth pressures), and transthoracic ultrasound (lung comet tails, cardiac function). Data from eight female finishers (age = 36.6 ± 6.9 yr; finish time = 30:57 ± 11:36 h:min) were compared with a group of eight time-matched males (age = 40.3 ± 8.3 yr; finish time = 30:46 ± 10:32 h:min). RESULTS: Females exhibited significant pre- to postrace increases in BNP (25.8 ± 14.6 vs 140.9 ± 102.7 pg·mL -1 ; P = 0.007) and CK-MB (3.3 ± 2.4 vs 74.6 ± 49.6 IU·L -1 ; P = 0.005), whereas males exhibited significant pre- to postrace increases in BNP (26.6 ± 17.5 vs 96.4 ± 51.9 pg·mL -1 ; P = 0.002), CK-MB (7.2 ± 3.9 vs 108.8 ± 37.4 IU·L -1 ; P = 0.002), and Cr (1.06 ± 0.19 vs 1.23 ± 0.24 mg·dL -1 ; P = 0.028). Lung function declined in both groups, but males exhibited additional reductions in lung diffusing capacities (DL CO = 34.4 ± 5.7 vs 29.2 ± 6.9 mL⋅min -1 ⋅mm Hg -1 , P = 0.004; DL NO = 179.1 ± 26.2 vs 152.8 ± 33.4 mL⋅min -1 ⋅mm Hg -1 , P = 0.002) and pulmonary capillary blood volumes (77.4 ± 16.7 vs 57.3 ± 16.1 mL; P = 0.002). Males, but not females, exhibited evidence of mild postrace pulmonary edema. Pooled effect sizes for within-group pre- to postrace changes, for all variables, were generally larger in males versus females ( d = 0.86 vs 0.63). CONCLUSIONS: Ultramarathon negatively affects a range of physiological functions but generally evokes more frequent perturbations, with larger effect sizes, in males compared to females with similar race performances.

Cardiopulmonary Outcomes After the Nuss Procedure in Pectus Excavatum.

Background Pectus excavatum is the most common chest wall deformity. There is still controversy about cardiopulmonary limitations of this disease and benefits of surgical repair. This study evaluates the impact of pectus excavatum on the cardiopulmonary function of adult patients before and after a modified minimally invasive repair. Methods and Results In this retrospective cohort study, an electronic database was used to identify consecutive adult (aged ≥18 years) patients who underwent cardiopulmonary exercise testing before and after primary pectus excavatum repair at Mayo Clinic Arizona from 2011 to 2020. In total, 392 patients underwent preoperative cardiopulmonary exercise testing; abnormal oxygen consumption results were present in 68% of patients. Among them, 130 patients (68% men, mean age, 32.4±10.0 years) had post-repair evaluations. Post-repair tests were performed immediately before bar removal with a mean time between repair and post-repair testing of 3.4±0.7 years (range, 2.5-7.0). A significant improvement in cardiopulmonary outcomes (P<0.001 for all the comparisons) was seen in the post-repair evaluations, including an increase in maximum, and predicted rate of oxygen consumption, oxygen pulse, oxygen consumption at anaerobic threshold, and maximal ventilation. In a subanalysis of 39 patients who also underwent intraoperative transesophageal echocardiography at repair and at bar removal, a significant increase in right ventricle stroke volume was found (P<0.001). Conclusions Consistent improvements in cardiopulmonary function were seen for pectus excavatum adult patients undergoing surgery. These results strongly support the existence of adverse cardiopulmonary consequences from this disease as well as the benefits of surgical repair.

Comparative study of a novel portable indirect calorimeter to a reference breath-by-breath instrument and its use in telemedicine settings.

BACKGROUND & AIMS: Resting Energy Expenditure (REE) quantitatively describes the calories used to support body function (e.g. breathing, blood circulation, etc.) at resting condition. Assessment of the REE is essential for successful weight management and the understanding of metabolic health. REE is typically determined via indirect calorimetry. Current biomedical indirect calorimetry technologies, utilizing assessment of oxygen consumption (VO2) and carbon dioxide production (VCO2) rates (which are typically in the form factor of a metabolic cart) are bulky and require on-site calibration and/or trained professionals to operate. We introduce a novel wearable medical device with FDA clearance to determine REE accurately, portable, and user-friendly format, which can be used both by health professionals in a clinical environment and by the patient at home. Previously, we have reported the validation of Breezing Med (also named as Breezing Pro™) through Douglas Bag Method, a gold standard for gas exchange measurement, and excellent agreement has been found between the two methods for the determination of REE, VO2, and VCO2 rates (Mora et al., 2020). Now we present the validation of Breezing Med against Medical Graphics (MGC) CPX Ultima™, a FDA 510 k cleared metabolic cart, which principle is based on breath-by-breath analysis. In addition, we present Breezing Med as a tool for daily measurement of metabolic rate by the lay person at home. METHODS: A) The validation study was executed via parallel measurement of 20 healthy participants under resting conditions using both the Breezing Med and the MGC Ultima CPX™ (10 min test). B) Breezing Med measurements were carried out by six subjects at home during stay-at-home order due to COVID-19 for 30 days. RESULTS: A) The resulting measurements from both devices was compared with correlation slope's and R-squared coefficients close to 1. B) Results were recorded and analyzed for variability. The pilot study demonstrated the advantage of Breezing Med device to be easy-to-use at home by lay people, which make the valuable device for telemedicine applications related to weight management from home. CONCLUSIONS: This result shows that the MGC Ultima CPX™ and Breezing Med are substantially equivalent for REE measurement; and an advantage of this device for metabolic assessment under the current COVID-19 pandemic situation, for people with impaired physical mobility, and for those who lives in rural areas or face impediments that limit physical access to care.

The Influence of Social Distancing Behaviors and Psychosocial Factors on Physical Activity During the COVID-19 Pandemic: Cross-sectional Survey Study.

BACKGROUND: The COVID-19 pandemic has arguably facilitated a shift toward increased sedentariness and reduced physical activity. Moreover, there is mounting evidence that mental health has also declined during the pandemic. However, it remains unknown to what extent social distancing (SD) behaviors and mental health have affected the physical activity levels of the general population. OBJECTIVE: The purpose of this study was to determine the influence of SD behaviors and prevailing mental health on the odds of being physically active during the early COVID-19 pandemic response. METHODS: A total of 4819 adults (2474/4819, 51.3%, female) from the US population with a median age of 46 (IQR 35-59) completed an online survey during the early pandemic response (April-June 2020). The survey included questions on adherence to 11 SD behaviors, and validated questionnaires which assessed self-reported physical activity, depression, anxiety, and mental well-being. Respondents were categorized into 2 physical activity groups: inactive (0-599 metabolic equivalent of task [MET]-minutes/week) and active (≥600 MET-minutes/week). A logistic generalized additive model (GAM) was used to determine which SD factors and mental health outcomes were associated with physical activity level. RESULTS: The GAM analysis revealed that wearing a facemask in public (odds ratio [OR] 1.46, 95% CI 1.14-1.79; P=.003), limiting the use of public transport (OR 1.47, 95% CI 1.19-1.83; P=.001), and restricting travel outside the house (OR 1.56, 95% CI 1.19-2.05; P=.002) were SD behaviors associated with higher odds of being more physically active. Conversely, avoiding physical activity outside the house was associated with higher odds of being inactive (OR 0.52, 95% CI 0.46-0.63; P<.001). Leaving the house more frequently, and a higher mental well-being were associated with increasing odds of being physically active (P<.001). Engaging with a moderate number of SD behaviors (3-7 total) was positively associated with physical activity, whereas a very high SD vigilance (ie, engaging with ≥10 total behaviors) decreased the odds of being active during the early pandemic response. CONCLUSIONS: Based on the findings of our study, we suggest that future public health messaging of SD guidelines should include (1) a clear portrayal of the benefits of regular exercise on mental health; and (2) a specific focus on how to be physically active outdoors in a COVID-safe manner.

Exercise and the immune system: taking steps to improve responses to cancer immunotherapy.

The remarkable success of cancer immunotherapies has provided new hope to cancer patients. Unfortunately, a significant proportion of patients remain unable to respond to immunotherapy or maintain durable clinical responses. The lack of objective responses likely results from profound immune dysfunction often observed in patients with cancer. There is substantial evidence that exercise and physical activity can reduce incidence and improve outcomes in cancer patients. As the immune system is highly responsive to exercise, one potential avenue to improve immune function is through exercise and physical activity. A single event of dynamic exercise results in the substantial mobilization of leukocytes with increased functional capacities into the circulation. Chronic, or long-term, exercise leads to higher physical fitness in terms of greater cardiorespiratory function and/or muscle strength and endurance. High aerobic capacity, as measured by maximal oxygen uptake, has been associated with the reduction of dysfunctional T cells and improvements in the abundance of some T cell populations. To be sure, however, the mechanisms of exercise-mediated immune changes are both extensive and diverse. Here, we examine the evidence and theorize how acute and chronic exercise could be used to improve responses to cancer immunotherapies including immune checkpoint inhibitors, dendritic cell vaccines, natural killer cell therapies, and adoptive T cell therapies such as chimeric antigen receptor (CAR) T cells. Although the parameters of optimal exercise to yield defined outcomes remain to be determined, the available current data provide a compelling justification for additional human studies and clinical trials investigating the adjuvant use of exercise in immuno-oncology.

Alveolar to arterial gas exchange during constant-load exercise in healthy active men and women.

Inadequate hyperventilation and inefficient alveolar to arterial gas exchange are gas exchange challenges that can limit capacity and cause exercise-induced arterial hypoxaemia (EIAH). This work evaluated if the prevalence of gas exchange inefficiencies, defined as AaDO2>25 mmHg, PaCO2>38 mmHg, and/or ΔPaO2>-10 mmHg at any point during constant-load exercise in healthy, active, but not highly trained, individuals suggested an innate sex difference that would make females more susceptible to EIAH. Sixty-four healthy, active males and females completed 18-min of cycling exercise (moderate and vigorous intensity, 9 min/stage). Arterial blood gases were measured at rest and every 3-min during exercise, while constantly assessing gas exchange. Both sexes demonstrated similar levels of AaDO2 widening until the final 3 min of vigorous exercise, where females demonstrated a trend for greater widening than males (16.3±6.2 mmHg vs. 19.1±6.0 mmHg, p=0.07). Males demonstrated a blunted ventilatory response to moderate exercise with higher PaCO2 (38.5±2.6 vs. 36.5±2.4, p=0.002) and a lower ventilation when corrected for workload (0.42±0.1 vs. 0.48±0.1, p=0.002). No significant arterial hypoxaemia occurred, but in 6 M and 5 F SaO2 dropped by ≥2%. There was no difference in prevalence of pulmonary gas exchange inefficiencies between sexes, but the type of inefficiency was influenced by sex.Abbreviations: AaDO2: alveolar-arterial oxygen difference; BP: blood pressure; EIAH: exercise-induced arterial hypoxaemia; F: females; HR: heart rate; M: males; Q: cardiac output; PaCO2: arterial partial pressure of carbon dioxide; PaO2: arterial partial pressure of oxygen; ΔPaO2: change in arterial partial pressure of oxygen; PAO2: alveolar partial pressure of oxygen; RPE: rating of perceived exertion; SaO2: arterial oxygen saturation; VE: ventilation; VE/VCO2: ventilatory equivalent for carbon dioxide; VO2PEAK: peak oxygen consumption; WMAX: workload maximum.

Validation of radiofrequency determined lung fluid using thoracic CT: Findings in acute decompensated heart failure patients.

BACKGROUND: Noninvasive outpatient monitoring for heart failure (HF) has significant opportunity to reduce patient morbidity and the costs associated with recurrent hospitalization. The purpose of this study was to validate the ability of radiofrequency (RF) to assess lung fluid via a wearable patch device compared to thoracic CT in order to characterize volume overload. METHODS: 120 subjects were studied: 66 acute heart failure (AHF) inpatients and 54 subjects without AHF (Control - 44 healthy and 10 stable HF). All underwent supine thoracic CT scans and supine RF readings from the wearable patch device placed on the left mid-axillary line (age = 74 ± 16 vs. 57 ± 15 yrs.; female = 38 vs. 44%; BMI = 33.2 ± 9.0 vs. 27.3 ± 5.1, AHF vs. Control respectively). Reflected RF signals and subject-specific anthropometric data were used to calculate the RF-determined lung fluid content. CT Lung fluid was reported as percentage of lung volume. Classification analyses were used to compare RF and CT performance. RESULTS: AHF presented with higher lung fluid than controls by both CT and RF (CT: 20.1 ± 4.2% vs. 15.4 ± 2.4%; RF: 20.7 ± 5.6% vs. 15.6 ± 3.3%; p < 0.05 for all). The correlation between lung fluid measured by CT vs. RF was r = 0.7 (p < 0.001). RF determined lung fluid performed as well as CT in distinguishing AHF from control subjects: Sensitivity: 70% vs. 86%; Specificity: 82% vs. 83%; Positive Predictive Value: 82% vs. 86%; Negative Predictive Value: 69% vs. 83%, CT vs. RF respectively. CONCLUSIONS: Noninvasive nonionizing RF determined lung fluid provides a potential alternative to other measures for diagnosing and monitoring pulmonary fluid overload.

Fetal Origins of Asthma: A Longitudinal Study from Birth to Age 36 Years.

Rationale: Deficits in infant lung function-including the ratio of the time to reach peak tidal expiratory flow to the total expiratory time (tptef/te) and maximal expiratory flow at FRC (V̇maxFRC)-have been linked to increased risk for childhood asthma.Objectives: To examine the individual and combined effects of tptef/te and V̇maxFRC in infancy on risk for asthma and abnormalities of airway structure into mid-adult life.Methods: One hundred eighty participants in the Tucson Children's Respiratory Study birth cohort had lung function measured by the chest-compression technique in infancy (mean age ± SD: 2.0 ± 1.2 mo). Active asthma was assessed in up to 12 questionnaires between ages 6 and 36 years. Spirometry and chest high-resolution computed tomographic (HRCT) imaging were completed in a subset of participants at age 26. The relations of infant tptef/te and V̇maxFRC to active asthma and airway structural abnormalities into adult life were tested in multivariable mixed models.Measurements and Main Results: After adjustment for covariates, a 1-SD decrease in infant tptef/te and V̇maxFRC was associated with a 70% (P = 0.001) and 55% (P = 0.005) increased risk of active asthma, respectively. These effects were partly independent, and two out of three infants who were in the lowest tertile for both tptef/te and V̇maxFRC developed active asthma by mid-adult life. Infant V̇maxFRC predicted reduced airflow and infant tptef/te reduced HRCT airway caliber at age 26.Conclusions: These findings underscore the long-lasting effects of the fetal origins of asthma, support independent contributions by infant tptef/te and V̇maxFRC to development of asthma, and link deficits at birth in tptef/te with HRCT-assessed structural airway abnormalities in adult life.

Impact of pulsed electromagnetic field therapy on vascular function and blood pressure in hypertensive individuals.

The present study investigated the impact of 12 weeks of pulsed electromagnetic field (PEMF) therapy on peripheral vascular function, blood pressure (BP), and nitric oxide in hypertensive individuals. Thirty hypertensive individuals (SBP > 130 mm Hg and/or MAP > 100 mm Hg) were assigned to either PEMF group (n = 15) or control group (n = 15). During pre-assessment, participants underwent measures of flow-mediated dilation (FMD), BP, and blood draw for nitric oxide (NO). Subsequently, they received PEMF therapy 3x/day for 12 weeks and, at conclusion, returned to the laboratory for post-assessment. Fifteen participants from the PEMF group and 11 participants from the control group successfully completed the study protocol. After therapy, the PEMF group demonstrated significant improvements in FMD and FMDNOR (normalized to hyperemia), but the control group did not (P = .05 and P = .04, respectively). Moreover, SBP, DBP, and MAP were reduced, but the control group did not (P = .04, .04, and .03, respectively). There were no significant alterations in NO in both groups (P > .05). Twelve weeks of PEMF therapy may improve BP and vascular function in hypertensive individuals. Additional studies are needed to identify the mechanisms by which PEMF affects endothelial function.

Effects of an allosteric hemoglobin affinity modulator on arterial blood gases and cardiopulmonary responses during normoxic and hypoxic low-intensity exercise.

Numerous pathophysiological conditions induce hypoxemia-related cardiopulmonary perturbations, decrements in exercise capacity, and debilitating symptoms. Accordingly, this study investigated the efficacy of an allosteric hemoglobin modulator (voxelotor) to enhance arterial oxygen saturation during low-intensity exercise in hypoxia. Eight normal healthy subjects (36 ± 7 yr; 73.8 ± 9.5 kg; 3 women) completed a submaximal cycling test (60 W) under normoxic ([Formula: see text]: 0.21; O2 partial pressure: 144 mmHg) and hypoxic ([Formula: see text]: 0.125; O2 partial pressure: 82 mmHg) conditions before (day 1) and after (day 15) 14 days of oral drug administration. While stationary on a cycle ergometer and during exercise, ratings of perceived exertion (RPE) and dyspnea, oxygen consumption (V̇o2), and cardiac output (Q) were measured noninvasively, while arterial blood pressure (MAP) and blood gases ([Formula: see text], [Formula: see text], and [Formula: see text]) were measured invasively. The 14-day drug administration left shifted the oxygen-hemoglobin dissociation curve (ODC; p50 measured at standard pH and Pco2; day 1: 28.0 ± 2.1 mmHg vs. day 15: 26.1 ± 1.8 mmHg, P < 0.05). RPE, dyspnea, V̇o2, Q, and MAP were not different between day 1 and day 15. [Formula: see text] was similar during normoxia on day 1 and day 15 while stationary but higher during exercise (day 1: 95.2 ± 0.4% vs. day 15: 96.6 ± 0.3%, P < 0.05). [Formula: see text] was higher during hypoxia on day 15 while stationary (day 1: 82.9 ± 3.4% vs. day 15: 90.9 ± 1.8%, P < 0.05) and during exercise (day 1: 73.6 ± 2.5% vs. day 15: 84.8 ± 2.7%, P < 0.01). [Formula: see text] and [Formula: see text]were systematically higher and lower, respectively, after drug (P < 0.01), while the alveolar-arterial oxygen difference was unchanged suggesting hyperventilation contributed to the rise in [Formula: see text]. Oral administration of voxelotor left shifted the ODC and stimulated a mild hyperventilation, leading to improved arterial oxygen saturation without altering V̇o2 and central hemodynamics during rest and low-intensity exercise. This effect was more pronounced during submaximal hypoxic exercise, when arterial desaturation was more evident. Additional studies are needed to determine the effects of voxelotor during maximal exercise and under chronic forms of hypoxia.NEW & NOTEWORTHY In humans, a novel allosteric hemoglobin-oxygen affinity modulator was administered to comprehensively examine the cardiopulmonary consequences of stabilizing a portion of the available hemoglobin in a high-oxygen affinity state during submaximal exercise in normoxia and hypoxia. Oral administration of voxelotor enhanced arterial oxygen saturation during submaximal exercise without altering oxygen consumption and central hemodynamics; however, the partial pressure of arterial carbon dioxide was reduced and the partial pressure of arterial oxygen was increased implying that hyperventilation also contributed to the increase in oxygen saturation. The preservation of arterial oxygen saturation and content was particularly evident during hypoxic submaximal exercise, when arterial desaturation typically occurs, but this did not influence arterial-venous oxygen difference.

Myocardial adaptability in young and older-aged sea-level habitants sojourning at Mt Kilimanjaro: are cardiac compensatory limits reached in older trekkers?

INTRODUCTION: High-altitude ascent induces left (LV) and right (RV) ventricular adaptations secondary to hypoxia-related hemodynamic and myocardial alterations. Since cardiopulmonary decrements observed with aging (e.g., decreased LV compliance and increased pulmonary vascular resistance) may limit cardiac plasticity, this study examined myocardial adaptability throughout an 11 day sojourn to 5893 m in young and older-aged trekkers. METHODS AND RESULTS: Echocardiography was performed on 14 young (8 men; 32 ± 5 years) and 13 older-aged (8 men; 59 ± 5 years) subjects on non-trekking days (Day 0: 880 m; Day 3: 3100 m; Day 8: 4800 m; Day 12/post-climb: 880 m). RV systolic pressure (mmHg) was systematically higher in older-aged subjects (p < 0.01) with similar progressive increases observed during ascent for young and older subjects, respectively (Day 0: 18 ± 1 vs 20 ± 2; Day 3: 25 ± 2 vs 29 ± 3; Day 8: 30 ± 2 vs 35 ± 2). Estimates of LV filling pressure (E/E') were systematically higher in older subjects (p < 0.01) with similar progressive decreases observed during ascent for young and older-aged subjects, respectively (Day 0: 5.6 ± 0.3 vs 6.7 ± 0.5; Day 3: 5.1 ± 0.2 vs 6.1 ± 0.3; Day 8: 4.7 ± 0.3 vs 5.4 ± 0.3). Overall, RV end-diastolic and end-systolic area increased at altitude (p < 0.01), while LV end-diastolic and end-systolic volume decreased (p < 0.01). However, all RV and LV morphological measures were similar on Day 3 and Day 8 (p > 0.05), and returned to baseline post-climb (p > 0.05). Excluding mild LV dilatation in some older-aged trekkers on Day 8/Day 12 (p < 0.01), altitude-induced morphological and functional adaptations were similar for all trekkers (p > 0.05). CONCLUSION: Altitude-induced myocardial adaptations are chamber specific, secondary to RV and LV hemodynamic alterations. Despite progressive hemodynamic alterations during ascent, morphological and functional cardiac perturbations plateaued, suggesting rapid myocardial adaptation which was mostly comparable in young and older-aged individuals.

The impact of pulsed electromagnetic field therapy on blood pressure and circulating nitric oxide levels: a double blind, randomized study in subjects with metabolic syndrome.

Purpose: Regulation of blood pressure (BP) is important in reducing the risk for cardiovascular disease. There is growing interest in non-pharmacological methods to treat BP including a novel approach using pulsed electromagnetic field therapy (PEMF). PEMF therapy has been proposed to impact physiological function at the cellular and tissue level and one possible mechanism is through an impact on endothelial function and nitric oxide (NO) related pathways. The focus of the present study was to evaluate the effect of PEMF on BP and NO in subjects with mild to moderate metabolic syndrome.Materials and methods: For 12 weeks, 23 subjects underwent PEMF therapy and 21 subjects underwent sham therapy. BP was measured at rest and near the end of submaximal exercise pre- and 12 week post-therapy. Additionally, plasma NO was measured at similar time points.Results: The PEMF demonstrated an increase in NO after therapy (p = .04) but SHAM did not (p = .37). For resting BP, there were no differences in systolic BP (SBP), diastolic BP (DBP) or mean arterial pressure (MAP) between groups (p > .05). During exercise, PEMF had a reduction in peak SBP (p = .04), but not SHAM (p = .57). PEMF demonstrated significant relationships between baseline SBP and change in SBP following therapy (r = -0.71, p < .01) and between MAP and change in MAP following therapy (r = -0.60, p < .01), but no such relationships were found in SHAM. Subjects with resting hypertension (SBP ≥140 mmHg) in PEMF (n = 11) had significant reductions in SBP, DBP and MAP when compared to SHAM with hypertension (n = 9) (p < .05). In this sub-group analysis, PEMF demonstrated lowered peak SBP (p = .04) at a given exercise load (p = .40) but SHAM did not (p > .05).Conclusion: PEMF may increase plasma NO availability and improve BP at rest and during exercise. However, this beneficial effect appears to be more pronounced in subjects with existing hypertension.

Relationship of Activity Patterns to Acute Mountain Sickness in South Pole Workers.

This study aimed to evaluate the influence of physical activity on incidence of acute mountain sickness (AMS) by continuous activity monitoring in a free-living sample of South Pole workers over the initial 72 h at altitude exposure of 2,840 m (9,318 ft). Body Media activity monitors were worn by 47 healthy participants. AMS was defined by the Lake Louise symptom questionnaire. Venous blood samples were taken at sea level and approximately 48 h after high altitude exposure. AMS incidence was 34% (n=16/47) over the first 48 h and 40% (n=19/47) over 72 h. On day 2 at high altitude, individuals with AMS demonstrated a significantly greater increase in the percent change in physical activity metrics from baseline: total energy expenditure 19±13 vs. 5±7%, total steps 65±51 vs. 10±18%, metabolic equivalent of tasks 21±13 vs. 7±13%, and time spent performing moderate to vigorous physical activity 114±79 vs. 26±27% for individuals with AMS vs. no AMS, respectively, p<0.05. In addition, erythropoietin and vascular endothelial growth factor were 1.69 and 1.75 times higher, respectively, in those with AMS. In conclusion, workers who engaged in increased physical activity and activity intensity during initial exposure to the South Pole were more susceptible to developing AMS.