Journal of applied physiology最新文献

Acute mountain sickness occurs due to rapid altitude ascents and/or insufficient acclimatization. Acetazolamide (AZ) is commonly prescribed for AMS prophylaxis but inhibits exercise performance. Methazolamide (MZ), an analogous drug, has similar prophylactic benefits but does not impair isolated muscle mass exercise performance in normoxia. We sought to compare whole-body exercise performance in acute hypoxia (F_IO₂ = 0.15) between AZ, MZ and placebo (PLA). Fifteen healthy participants completed 5 testing visits: day 1 maximal exercise test, day 2 a familiarization, and days 3-5 were the experimental visits. Each experimental visit involved a 5-km hypoxic cycling time trial performed after a 2-day dosing protocol of either AZ (250 mg t.i.d.), MZ (100 mg b.i.d.) or PLA (t.i.d.); the order was randomized and double-blinded. Prior to exercise, capillary blood samples were taken, and maximal voluntary contractions of quadriceps were performed. AZ and MZ resulted in a partially compensated metabolic acidosis at rest compared to PLA (capillary H⁺ 47±3, 43±2, 39±2 nmol for AZ, MZ and PLA respectively, p<0.01). Time to complete 5-km with PLA (562±32 seconds, p<0.01) was significantly faster than AZ and MZ (577±38 vs. 581±37s respectively), with no differences between AZ and MZ (p=0.96). There were no differences in average ventilation (124±27, 127±24, 127±19 l/min) and oxyhemoglobin saturation (87±2, 88±2, 88±3%) between AZ, MZ and PLA respectively (p>0.05). Overall, both AZ and MZ impair whole-body exercise performance in acute normobaric hypoxia.

Degradation of the endothelial glycocalyx in type 2 diabetes (T2D) is thought to contribute to impaired shear stress mechanotransduction, leading to endothelial dysfunction and the development of cardiovascular disease. Herein, we tested the hypothesis that restoration of the endothelial glycocalyx with dietary supplementation of glycocalyx precursors (DSGP, containing glucosamine sulfate, fucoidan, superoxide dismutase, and high molecular weight hyaluronan) improves endothelial function and other indices of vascular function in T2D. First, in db/db mice, we showed that treatment with DSGP (100 mg/kg/day) for four weeks restored endothelial glycocalyx length, as assessed via atomic force microscopy in aortic explants. Restoration of the glycocalyx with DSGP was accompanied by improved flow-mediated dilation (FMD) and reduced arterial stiffness in isolated mesenteric arteries. Further corroborating these findings, treatment of cultured endothelial cells with that same mixture of glycocalyx precursors promoted glycocalyx growth. Next, as an initial step to investigate the translatability of these findings, we conducted a pilot (n=22) double-blinded randomized placebo-controlled clinical trial to assess the effects of DSGP (3,712.5 mg/day) for eight weeks on endothelial glycocalyx integrity and indices of vascular function, including FMD, in Veterans with T2D. Contrary to the hypothesis, DSGP neither enhanced endothelial glycocalyx integrity nor improved vascular function indices relative to placebo. Together, these findings conceptually support the notion that restoration of the endothelial glycocalyx can lead to improvements in vascular function in a mouse model of T2D; however, DSGP as a therapeutic strategy to enhance vascular function in individuals with T2D does not appear to be efficacious.

Research on world-class athletes in endurance events, such as cycling Grand Tours, has reported extreme levels of total energy expenditure. However, it has been argued that over extended periods, such as months, sustained energy expenditure is capped at approximately 2.5 times the basal metabolic rate. Triathlon is particularly notable for its high energetic demands due to its multimodal nature, requiring athletes to maintain high training volumes. In this case study, we analyzed the total energy expenditure of world-class triathlete Kristian Blummenfelt using doubly labelled water over two specific periods, along with three years of training data. Total energy expenditure ranged from 7,019-8,506 kcal/day. Reported energy intake ranged from 4,899 to 6,360 kcal/day. The annual training volumes for the years 2020-2022 were 1,480, 1,350 and 1,308 hours, respectively, following a pyramidal intensity distribution. Approximately 53% of the entire three-year period matched with the doubly labeled water measurement periods in terms of training volume, indicating that the recorded total energy expenditure is representative of the majority of the observed data. Hence, the greater part of the three-year period likely exceeds the proposed metabolic ceiling for sustained total energy expenditure. This not only questions the validity of the current metabolic limits but also suggests a new perspective on what is physiologically achievable in world-class athletes.

Growth differentiation factor 15 (GDF15) is a stress-induced cytokine that increases with exercise and is thought to increase corticosterone and lipid utilization. How post-exercise nutrient availability impacts GDF15 and the physiological role that GDF15 plays during and/or in the recovery from exercise has not been elucidated. The purpose of this investigation was to examine how post-exercise nutrient availability impacts GDF15 and to use this as a model to explore associations between GDF15, corticosterone and indices of lipid and carbohydrate metabolism. In addition, we explored the causality of these relationships using GDF15 deficient mice. Male and female C57BL/6J mice ran for 2 hours on a treadmill and were sacrificed immediately or 3 hours after exercise with or without access to a chow diet. In both sexes, circulating concentrations of GDF15, corticosterone, non-esterified fatty acids (NEFA), and beta hydroxybutyrate (BHB) were higher immediately post-exercise and remained elevated when food was withheld during the recovery period. While serum GDF15 was positively associated with corticosterone, BHB and NEFA, increases in these factors were similar in wildtype and GDF15^-/- mice following exercise. The lack of a genotype effect was not explained by differences in insulin, glucagon or epinephrine after exercise. Our findings provide evidence that while GDF15 is associated with increases in corticosterone and indices of lipid utilization this is not a causal relationship.

Selective distribution of cerebral blood flow (CBF) to vital brain regions likely occurs during rapid severe hypotension caused by tachyarrhythmia, but has not yet been demonstrated. In this study, we aimed to test the hypothesis that CBF is differentially preserved between brain regions depending on the degree of hypotension. In anesthetized rats, CBF was measured in the motor cortex (MC), medial prefrontal cortex, amygdala, thalamus, dorsal hypothalamus, hippocampus, ventral tegmental area, dorsolateral periaqueductal gray (dlPAG), and parabrachial nucleus (PB) by using laser-Doppler flowmetry. Ventricular pacing was performed for 30 s at 550-800 beats/min. The cerebrovascular CO₂ response time and reactivity were evaluated during 5% CO₂ exposure. During 1-4 s of ventricular pacing, mean arterial pressure (MAP) rapidly decreased, with minor changes in central venous and intracranial pressures. CBF was relatively well maintained in brain regions other than the MC (Ps ≤ 0.012) when moderate hypotension occurred (-34 mmHg ≤ ΔMAP ≤ -15 mmHg), whereas severe hypotension (-54 mmHg ≤ ΔMAP ≤ -35 mmHg) induced selective CBF distribution to regions other than the MC, thalamus, and dlPAG. The cerebrovascular CO₂ response time/reactivity was rapid or high in the thalamus, dlPAG, and PB, which almost completely differed from the brain regions in which CBF was relatively maintained during pacing-induced severe hypotension. These results suggest that regional heterogeneity of CBF arises depending on the degree of tachyarrhythmia-induced hypotension. Clarifying the mechanisms and functions of CBF maintenance would be beneficial to syncope and cerebral ischemia management in patients with arrhythmia.

There is a lack of evidence regarding the safety of long-duration and vigorous intensity physical activity during pregnancy, such as that required during an ultramarathon. This case study is the first to examine the training, performance, health, and delivery outcomes for an ultramarathoner across two successive pregnancies (one twin and one singleton) that were delivered when the athlete was 41 and 43 years, respectively.. During her twin pregnancy, she ran an average of 91.72 ± 23.17 kilometers across 9.06 ± 2.38 hours per week. Both twins were normal for gestational age and delivered at 37 weeks. Twin B experienced mild hypoxic-ischemic encephalopathy, but made a full recovery following treatment. Twin pregnancy increases risk of this complication and there is no evidence to suggest that it is associated with vigorous intensity endurance activity. During her singleton pregnancy, the participant's distance and pace increased, running on average 157.80 ± 14.69 kilometers across 14.08 ± 1.60 hours per week. She also competed in 5 races including 3 ultramarathons and ranked well, with no adverse events during or following each of the races. She delivered prematurely (36 weeks and 6 days), but her baby was normal for gestational age.

Walking is a fundamental aspect of daily life and exercise, with clinical benefits for cardiovascular health and muscle strength. However, accurately measuring energy efficiency during walking poses challenges due to equipment and spatial constraints. In this study, we proposed the cadence-based energy expenditure index (cEEI) and analyzed its correlation with the previously proposed index for measuring energy expenditure under various gait conditions. We enrolled 15 healthy participants and conducted an experimental protocol on a treadmill to measure the following energy expenditure-related indices: oxygen cost index (OCI), energy expenditure index (EEI), and cEEI. The participants underwent stages of walking at different speeds and inclinations that comply with the modified Bruce protocol while their heart rate, oxygen uptake, and cadence were recorded. Participants showed significant increases in heart rate, oxygen uptake, and cadence with higher walking speeds and inclinations. Correlation analysis revealed strong associations between cEEI and OCI, especially during walking conditions. Bland-Altman plots and interclass correlation coefficient analysis demonstrated a favorable agreement between cEEI and OCI, outperforming EEI. In conclusion, this study proposes cEEI as a reliable metric for estimating energy expenditure during walking by proving a strong correlation and agreement with OCI across various gait conditions. This suggests the potential for cEEI to provide real-time, individualized feedback on energy expenditure during walking, facilitating more personalized exercise prescriptions.

There are known sex differences in cardiorespiratory fitness (CRF). Little is known about the impact of pubertal blockade with a gonadotropin releasing hormone agonist (GnRHa) followed by hormone therapy on CRF for transgender adolescents. We aimed to (1) determine the effect of GnRHa monotherapy on CRF and mitochondrial function and associations with metabolomic profiles, and (2) evaluate for changes after 1 and 12 months of testosterone therapy among transgender adolescents . Participants assigned female at birth (n=19, baseline age 15.0+1.0 years) from two groups: GnRHa+ (n=8) and GnRHa- (n=11) were examined at baseline and 1- and 12-months post-testosterone therapy in a longitudinal observational study to assess cardiorespiratory fitness, mitochondrial respiration and metabolic profile. Fasted morning labs including assessment of metabolomics and peripheral blood mononuclear cell mitochondrial respiration and degree of mitochondrial coupling (respiratory control ratio, RCR). A graded cycle ergometer test was performed. Baseline differences were evaluated between groups. Changes were compared with mixed linear regression models evaluating time (baseline, 1 and 12 months), group (GnRHa treatment yes/no), and their interaction. At baseline GnRHa+ individuals had higher relative VO₂peak (30.1+4.83 vs. 25.24+4.47 ml/kg/min, p=0.042) than GnRHa- individuals. In regression models, GnRHa+ individuals had a significant increase in peak watts (p=0.011) and total exercise time (p=0.005)after 12 months of testosterone (p=0.012), but not GnRHa- individuals. GnRHa+ individuals have significantly higher RCR under carbohydrate (p=0.0007) and lipid (p=0.0002) conditions than GnRHa+ individuals. Pretreatment with GnRHa positively influences peak CRF and mitochondrial respiration in adolescent transgender males undergoing testosterone therapy.

Hydraulic force, a novel mechanism shown to aid diastolic filling, can be calculated by assessing the geometrical relationship between the left ventricular and atrial short-axis areas (atrioventricular area difference, AVAD). During exercise both ventricular and atrial volumes change due to altered loading conditions compared to rest, but it is unknown to what extent this affects AVAD. The aim of this study was to investigate if AVAD differs when going from rest to exercise in sedentary controls and athletes. We included 13 sedentary controls and 20 endurance athletes to undergo cardiovascular magnetic resonance (CMR) imaging at rest and during moderate and vigorous exercise using a CMR-compatible ergometer. AVAD was calculated as the largest ventricular short-axis area minus the largest atrial short-axis area in end-diastole (ED) and end-systole (ES) as measured from CMR short-axis images. AVAD in ED increased during moderate exercise in both sedentary controls and athletes, thus aiding diastolic filling, but did not increase further during vigorous exercise. AVAD in ES was negative in both groups at rest and decreased further with increasing exercise intensity in sedentary controls, whereas athletes remained unchanged. In conclusion, results from AVAD in ED indicate the net hydraulic force to further augment diastolic filling during moderate exercise when compared to rest, providing new insights into the mechanism by which diastolic function increases during exercise.