Journal of applied physiology最新文献

Background: Heart failure (HF) is characterised by altered skeletal muscle morphology. The aim of this systematic review and meta-analysis was to explore cross-sectional differences in muscle morphology and metabolism between patients with HF and healthy controls. Methods: A literature search of studies was conducted from inception to February 2025 across PubMed, Scopus, Web of Science, and the Cochrane Library. Eligible studies compared skeletal muscle morphological differences via the vastus lateralis from patients with HF vs. healthy controls. A meta-analysis was conducted using the random effects inverse-variance model. Results: Thirty-five studies were included in this study. Patients with HF displayed similar absolute muscle fiber areas (type I, II, IIa, IIx), lower relative type I fiber area (MD: -8.3%, 95% confidence interval (95% CI): -12.3 to -4.4), and higher type II (MD: 11.3%, 95% CI: 7.3 to 15.4) and IIx areas (MD: 7.4%, 95% CI: 4.3 to 10.4) vs. healthy controls. Capillaries per fiber were reduced in HF (MD = -0.28, 95% CI: -0.52 to -0.03), particularly for type IIa (MD = -0.30, 95% CI: -0.54 to -0.06) and IIx fibers (MD = -0.35, 95% CI: -0.55 to -0.15). IGF-1 was lower (-19.4 mRNA AU, 95% CI: -36.3 to -2.5), and myostatin was elevated (16.1 mRNA AU, 95% CI: 2.9 to 29.2) in HF. Citrate synthase, 3-hydroxyacyl-CoA-dehydrogenase, and succinate dehydrogenase were significantly lower in HF (p < 0.05). Conclusions: In HF, reduced relative type I fiber area, increased type II/IIx, reduced capillarization, altered anabolic/catabolic markers, and impaired energy metabolism enzymes, were observed compared to controls.

Background: Neurological injury, the leading cause of death after cardiac arrest resuscitation, has been shown to worsen progressively in the post-cardiac arrest period. This deterioration may be due to impaired cerebral autoregulation, leading to harmful alterations in cerebral perfusion. We aimed to investigate the myogenic response, a key component of cerebral autoregulation, in the post-cardiac arrest period. Method: Rats were anesthetized, intubated, catheterized, and randomized into a sham group or cardiac arrest group. Cardiac arrest rats underwent 7 minutes of cardiac arrest. Subsequently, groups were observed for 4 hours. Middle cerebral arteries (MCAs) were examined utilizing pressure myography and confocal microscopy. qPCR was performed on the posterior communicating arteries. Results: The myogenic response to increasing levels of intraluminal pressure was significantly reduced in MCAs from cardiac arrest rats compared with sham (p=0.02, mixed model for repeated measures). The MCAs demonstrated comparable contraction to increasing concentrations of U46619, but a high K⁺ solution yielded significantly lower vasoconstriction in cardiac arrest MCAs compared with sham (sham: 152±5 µm and cardiac arrest: 166±3 µm, p=0.03). qPCR showed reduced gene expression of cytoplasmic tyrosine kinase ABL1, rho-associated protein kinase 1, and endothelial NO synthase in cerebral arteries from cardiac arrest rats compared with sham. Confocal microscopy revealed no significant differences in nitrotyrosine or F-actin expression between groups in MCAs. Conclusion: In rat MCAs, the myogenic response, myogenic tone, and the maximum contraction are significantly reduced 4 hours after cardiac arrest. Our results suggest impaired calcium-sensitizing mechanisms in cerebral myogenic vasoconstriction after cardiac arrest.

The genioglossus (GG) muscle of the tongue, innervated by hypoglossal motoneurons, plays a critical role in the pathophysiology of obstructive sleep apnea. The state-dependent activity of the hypoglossal motoneurons is largely maintained by excitatory noradrenergic drive. However, this drive was hypothesized to be mediated by unidentified peri-hypoglossal neurons. We used microinjections of phenylephrine or prazosin, α1-adrenoceptor agonist and antagonist, respectively, into the medullary reticular formation rostral to the hypoglossal nucleus to locate these neurons. The phenylephrine or prazosin were microinjected into the hypoglossal nucleus and into rostral medullary regions while recording spontaneous activity in GG and diaphragm muscles in anesthetized C57bl/6J mice. The microinjections of phenylephrine/prazosin elicited respectively excitatory/inhibitory responses in the GG muscle, which had minimal latencies when injected into a limited region just rostral to the hypoglossal nucleus, which we termed the "pre-hypoglossal region" (PHR). In isoflurane-anesthetized mice, phenylephrine injected into the PHR induced large increases in GG muscle activity (21.8 ± 3.5 vs. baseline 4.50 ± 0.86, arbitrary units). These phenylephrine-induced responses from the PHR were substantially stronger compared to those evoked from the hypoglossal nucleus (5.46 ± 1.3 vs. baseline 4.12 ± 0.73). However, in ketamine/xylazine-anesthetized mice, phenylephrine's ability to activate the GG muscle from the PHR was substantially blunted, which suggests that the ketamine-induced systemic antagonism of glutamatergic NMDA receptors may interfere with the response. Our findings suggest that the PHR contains interneurons that mediate the state-dependent noradrenergic drive to hypoglossal motoneurons, and that glutamate may be used as mediator by PHR circuitry.

The upper limits for total energy expenditure (TEE) and water turnover (rH₂O) in humans have been reported during several continuous single-day ultra-endurance races (running, cycling, triathlon). Currently, the upper limits for TEE and rH₂O during continuous single-day activity in cold weather (<0C) remain unknown. The Arrowhead Ultra is one of the coldest ultra-endurance races in North America and provides a unique opportunity to answer these questions. Racers select a bicycle, cross-country skis, or foot travel to traverse a 214km snow-covered trail (altitude range 345-426m, 2,030m elevation gain). Historically, ~1/2 of the racers complete the event. In this case study, we assessed TEE and rH₂O from the racer (cyclist, age:22yrs, height:1.84m, body mass:87.7kg, VO_2max:5.0LO₂.min^-1) who won the 2025 Arrowhead Ultra (17.9hr, ^-13-^-1C) using the doubly labeled water method. Total energy and fluid intake were recorded to assess energy and fluid balance. Mean heart rate was 141bpm (71% of maximum heart rate). TEE was 63.9MJ (15,273kcals, 9.6x basal metabolic rate) while total energy intake was 33.2MJ (7,941kcal). Mean carbohydrate intake was 88g.hr^-1. Water turnover was 17.7L yielding a rH₂O/TEE ratio of 0.28L.MJ^-1 for the race. The cyclist demonstrated high TEE and rH₂O that were comparable to values from other ultra-endurance athletes competing in a range of temperatures (3-34C). Notably, rH₂O from this cyclist was higher compared to athletes performing other ultra-type endeavors in cold weather conditions (^-25-^-19C). Our observations shed light on energy and fluid demands during continuous single-day activity in the cold and have endurance training and performance implications.

In Acute Respiratory Distress Syndrome (ARDS), regional aeration is often gravity-dependent, with Positive End-Expiratory Pressure (PEEP) recruiting the lung dorsally. While recruitability can be assessed globally, our aim was to determine the impact of PEEP on regional recruitability and regional strain. To achieve a large representation of recruitability, we studied two preclinical porcine models of acute lung injury ([ALI] 19 symmetrical and 10 asymmetrical ALI), 20 patients with ARDS of mixed etiology (mixed ARDS) and 15 with COVID-19 ARDS. All study subjects underwent a single-breath derecruitment maneuver from high to low PEEP to quantify recruitability using the recruitment-to-inflation ratio (R/I). The regional effects of PEEP on strain were assessed using Electrical Impedance Tomography (EIT). Symmetrical ALI animals had the highest R/I (1.39[1.04-1.66]), followed by mixed ARDS (1.06[0.70-1.23]), COVID-19 ARDS (0.66[0.51-0.98]), and asymmetrical ALI (0.45[0.22-0.85]). Dorsal regions had the highest recruitability (p=0.001), and differences between dorsal and ventral regions were higher in recruitable subjects. Increasing PEEP decreased ventral dynamic strain (p<0.01), with varying effects on dorsal dynamic strain. A paradoxical increase in dorsal dynamic strain associated with ventral hyperinflation could be observed across all groups, but more frequently in the less recruitable subjects. It was predicted by the EIT ventral-to-dorsal shift in ventilation normalized to the change in dorsal lung volume (p<0.001). In animals and patients with varying recruitability, a higher global R/I is associated with a higher effect on the dorsal versus ventral R/I. PEEP can paradoxically increase dorsal strain due to ventral overdistention, and this is detectable by EIT.

Despite the evidence that responses to intermittent hypoxia (IH) vary between sexes, potentially underlying sex-specific comorbidities of sleep apnea, the roles that sex hormones play during exposure to IH in rodent models remain poorly defined. The Estradiol receptor ɑ (ERɑ), expressed in structures of the peripheral and central nervous system, contributes to autonomic regulations and control of arterial blood pressure, accordingly, we tested the hypothesis that ERα modulates respiratory and heart rate variability in male and female mice exposed to IH. We used adult wild-type (WT) and ERα knockout (ERαKO) mice of both sexes for whole-body plethysmography, arterial blood pressure and ECG recordings before and after 14 days of IH (6% O₂, 12 cycles/h, 12 h/day). Compared to males, WT females exhibited greater respiratory variability and higher apnea frequency before IH exposure. In females, ERα deletion increased body weight, and reduced post-sigh apnea frequency before IH exposure. In ANCOVA/GLM models, body weight was a significant negative covariate for post-sigh and spontaneous apneas before IH exposure, while sex and genotype effects were not significant after adjustment. IH exposure increased the mean and diastolic blood pressures only in WT males. IH also increased apneas frequency in WT females, an effect markedly reduced by ERɑ deletion. Similarly, heart rate variability increased in WT females following IH, reflecting enhanced parasympathetic modulation, an effect absent in ERαKO females and in WT or ERαKO males. We conclude that in female mice, deletion of ERα prevents IH-induced improvement of heart rate variability.

Fatiguing contractions performed with limited oxygen supply develop a higher neuromuscular fatigue, perceived effort, and muscle pain that reduce exercise capacity. Despite these consistent observations, there is limited information about motor unit (MU) behavior in response to limited oxygen supply. Fourteen healthy participants (means ± SD age, 29 ± 5 yr; height, 175 ± 7 cm; mass, 75 ± 11.1 kg) were recruited. Neuromuscular function, perceived effort, muscle pain, and MU behavior were monitored during isometric contractions of the dominant ankle dorsiflexors at 60% of maximal voluntary contraction (MVC), with blood flow restriction (BFR) and without (Control). High-density surface electromyography was used to investigate MU behavior of the tibialis anterior muscle. MU were tracked across contractions and classified as relatively lower-threshold (≤30% MVC) and higher-threshold (> 30% MVC). During exercise with BFR, heart rate, perceived effort, and muscle pain were higher (P < 0.001). BFR induced greater neuromuscular fatigue, reduced maximal muscle activation, and muscle contractile function (P < 0.001). The discharge rate of lower-threshold MU decreased (P < 0.001), whereas it increased for higher-threshold MU (P ≤ 0.003). Both MU types exhibited reduced recruitment and derecruitment thresholds with BFR (P < 0.001). These results show disparate adjustment between lower- and higher-threshold MU during exercise with limited oxygen supply. Higher discharge rate of relatively higher-threshold MU might be required to compensate for the lower discharge rate of relatively lower-threshold MU. This suggests that the nervous system adopts an acute neural strategy to maintain force production during contractions with limited oxygen supply.NEW & NOTEWORTHY The behavior of motor units during high-intensity fatiguing contractions with limited oxygen supply is poorly investigated. Here, we show that during fatiguing exercise with blood flow restriction, motor units are recruited at lower force levels with inhibition of relatively lower-threshold motor units and increased activity of relatively higher-threshold motor units. These changes in motor unit behavior might represent an acute neural adaptation to produce force during high-intensity contractions with limited oxygen supply.

Concurrent training is commonly associated with blunted muscle hypertrophy compared with resistance training alone, but the underlying physiological mechanisms remain unclear. This study aimed to investigate the acute and chronic effects of concurrent versus resistance training on muscle protein synthesis, satellite cell dynamics, myonuclear content, myogenic regulatory factor expression, muscle fiber hypertrophy, strength, and aerobic capacity. Nineteen previously untrained young men were randomly assigned to either concurrent or resistance training for 16 wk. Muscle biopsies were collected before and 48 h after a standardized exercise session at weeks 4 and 16. Samples were analyzed for myofibrillar protein synthesis via deuterium oxide incorporation, satellite cell content, myonuclear number, and gene expression. Strength, aerobic capacity, and muscle fiber cross-sectional area were measured at baseline and postintervention. Muscle protein synthesis increased 48 h postexercise at both weeks 4 and 16 (P = 0.0105), with no group differences. Satellite cell content increased over time in type II fibers only (P = 0.0021). Myonuclear number increased in both fiber types (type I: P = 0.0301 and type II: P = 0.0009), with higher values in type I fibers in the concurrent training group (P = 0.0027). MYF5 and MYF6 expression increased over time (P = 0.0141 and P = 0.034, respectively), and MYOD1 was elevated postexercise only in concurrent training (P = 0.0009). Type II fiber size increased (P = 0.016). Strength gains were greater in resistance training (P = 0.016), whereas aerobic capacity improved only in concurrent training (P < 0.001). Sixteen weeks of concurrent training did not inhibit molecular mechanisms associated with muscle hypertrophy in previously untrained individuals.NEW & NOTEWORTHY Sixteen weeks of concurrent training with long-interval HIIT preserved key molecular adaptations related to muscle hypertrophy, including protein synthesis, satellite cell activity, and gene expression. Both concurrent and resistance training increased type II fiber cross-sectional area, but only concurrent training improved V̇o_2peak. Although strength gains were lower with concurrent training, molecular and cellular remodeling remained intact, supporting it as an effective strategy to enhance both muscle growth and aerobic fitness simultaneously.

The goal was to explore the impact of fluctuating female sex hormone concentrations on the work rate delineating sustainable from unsustainable work rates at the heavy to severe domain boundary or maximal metabolic steady state (MMSS). Thirty endurance-trained participants (15 F/15 M; V̇o_2max 48.1 ± 5.2 vs. 57.3 ± 5.3 mL·min^-1·kg^-1; P = 0.001) completed four MMSS estimation protocols at distinct sex hormone profiles. Serum sex hormone concentrations, specifically estradiol, progesterone, and testosterone, were determined during each study visit. To identify MMSS at each hormone profile, participants completed a muscle oxygenation (%SmO₂) zero-slope prediction cycling protocol once a week for 4 wk. The %SmO₂ zero-slope protocol consisted of four, 4-min stages (2-min rest) spanning intensity domains. The work rate associated with MMSS was determined using linear regression analysis between workload and %SmO₂ signal slope during the final 2 min of each stage. Linear mixed models showed male sex to be a significant predictor of power at MMSS (P < 0.001), but changes in sex hormone concentrations were not associated with changes in MMSS work rate. No sex differences in MMSS were found when normalized to lean body mass (LBM) (P = 0.224) nor across the four visits (P = 0.074). The LBM normalized work rate at MMSS was similar between men and women. Fluctuations in sex hormone profile in women were not associated with differences in the heavy to severe exercise domain boundary, nor were there any observed sex differences across distinct hormone profiles.NEW & NOTEWORTHY Our study examined the effects of fluctuating sex hormone concentration, rather than menstrual cycle phase, on the maximal metabolic steady state in both men and women. In addition to no sex difference, acute fluctuations in hormone concentration do not impact the lean body mass normalized work rate at the heavy to severe domain boundary in women. Direct measures of sex hormones are important to account for the potential impact of these hormones on physiological outcomes.