Journal of applied physiology最新文献

Women are participating in military and athletic activities in the heat in increasing numbers, but potential sex differences in sequelae from exertional heat illness remain poorly understood. We tested the hypothesis that women suffering from exertional heat stroke (EHS) would have similar severity of organ damage biomarkers compared with men, as measured in a hospital setting. We studied women and men presenting with EHS to the emergency department at Fort Moore, GA. We measured creatinine (CR), creatine kinase (CK), alanine-transaminase (ALT), aspartate aminotransferase (AST), and estimated glomerular filtration rate (eGFR). Core temperature was also assessed by medical personnel. Biomarker data were obtained for 62 EHS cases (11 women). Men were significantly taller, and heavier, and had larger body mass index (BMI) and body surface area (P < 0.05 for all). The highest recorded body core temperature was not different between groups [women: 41.11°C (40.06, 41.67); men: 41.11°C (40.28, 41.72), P = 0.57]. Women had significantly lower peak CR [women: 1.39 (1.2, 1.48) m·dL^-1; men: 1.75 (1.53, 2.16) mg·dL^-1, P < 0.01] and peak CK [women: 584 (268, 2,412) U·L^-1; men: 2,183 (724, 5,856) U·L^-1, P = 0.02]. Peak ALT and AST were not different between groups; during recovery time points, ALT and AST were either similar or lower in women. Women spent approximately half as much time in the hospital following admittance compared with men. Our findings suggest that women may be less susceptible to organ injury resulting from EHS. Further research is necessary to understand the pathophysiology underlying these differences and how biomarkers of end-organ damage severity can differ between women and men following EHS.NEW & NOTEWORTHY We studied otherwise healthy women and men after exertional heat stroke in a military training environment. Peak values for biomarkers of kidney and muscle damage were lower in women compared with men despite similar (highest recorded) body core temperatures. During recovery, organ damage markers were similar or lower in women. These sex differences may indicate differences in the pathophysiology of responses, but more work is needed to clarify specific mechanisms.

This study compared the effects of linear (LP) and nonlinear (NLP) training periodization on cognitive functions, neurotrophic biomarkers [plasma brain-derived neurotrophic factor (BDNF), insulin-like growth factor-1 (IGF-1)], and cathepsin-B in patients with coronary artery disease (CAD). Forty-four patients with CAD reported to our laboratory on two occasions to undergo testing procedures before and after training sessions, and were then blindly randomized to NLP or LP for 36 training sessions. Visit 1 included blood samples and a maximal cardiopulmonary exercise testing to get maximal oxygen uptake (V̇o_2peak). Visit 2 included cognitive functions assessment. Thirty-nine patients completed the study (LP: n = 20, NLP: n = 19), with no observed changes in cognitive performances after the training intervention in either group. IGF-1 concentration decreased in both groups (time-effect: P < 0.001), whereas BDNF concentration increased (time-effect: P < 0.05) without group interaction, and cathepsin-B did not change after the intervention. Associations were found between ΔV̇o_2peak and ΔBDNF (R² = 0.18, P = 0.04), and ΔIGF-1 and Δshort-term/working memory (R² = 0.17, P = 0.01) in the pooled sample, with ΔIGF-1 and ΔBDNF accounting for 10% of the variance in Δshort-term/working memory. In the LP group, associations were found between ΔV̇o_2peak and ΔBDNF (R² = 0.45, P = 0.02), ΔBDNF and Δshort-term/working memory (R² = 0.62, P = 0.004), ΔIGF-1 and Δshort-term/working memory (R² = 0.31, P = 0.01), and ΔIGF-1 and Δexecutive function (R² = 0.22, P = 0.04). This study indicates that linear and nonlinear training periodization led to an increase in BDNF, and a decrease in IGF-1, without change in cognitive function in individuals with stable CAD.NEW & NOTEWORTHY We used a novel and supervised iso-energetic training, integrating both moderate- and high-intensity aerobic exercises. Our findings indicate that greater variation in training load did not yield cognitive enhancements, although both protocols exhibited positive effects on brain-derived neurotrophic factor (BDNF) levels. Moreover, this study establishes a clear positive association between short-term and working memory and neurotrophic biomarkers. In addition, the independent predictive value of change in insulin-like growth factor-1 (IGF-1) on improvement in short-term and working memory highlight the close relationship between neurotrophic markers and cognition. Consequently, our results advocate for exercise training interventions targeting neurotrophic biomarkers to enhance cognitive function among individuals with coronary artery disease.

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.