Journal of applied physiology最新文献

Although some studies report attenuated net muscle glycogenolysis with carbohydrate ingestion, others show no effect, possibly due to small sample sizes or methodological differences. Objective of this study is to determine whether carbohydrate ingestion during endurance exercise reduces net skeletal muscle glycogen use and to identify potential moderating factors. A meta-analysis was conducted using data from 31 studies, which included 48 unique effect sizes derived from crossover trials comparing carbohydrate versus placebo ingestion during prolonged endurance exercise. Standardized mean differences (SMDs) in net muscle glycogen use were calculated. A multilevel random-effects model accounted for repeated estimates within studies. Subgroup and meta-regression analyses tested potential moderators. Sensitivity analyses were conducted using a range of plausible pre-/postcorrelation values. Carbohydrate ingestion was associated with a small but statistically significant muscle glycogen-sparing effect [SMD = -0.16, 95% confidence interval (CI): -0.30 to -0.02, P = 0.021]. Subgroup and moderator analyses revealed no significant effects of exercise mode, carbohydrate type, ingestion rate, or preexercise glycogen on the observed effect. Translating the standardized effect into absolute units, carbohydrate ingestion was estimated to spare ∼24 mmol·kg^-1 dry wt (95% CI: 4-45 mmol·kg^-1) of muscle glycogen, relative to placebo, during ∼100 min of exercise. Carbohydrate ingestion during endurance exercise leads to a small but statistically significant reduction in net skeletal muscle glycogen utilization. Although no consistent moderating variables were identified, the direction of effect was consistent across studies, and the absolute magnitude of sparing may be physiologically meaningful during prolonged or repeated efforts.

This study aimed to elucidate the effects of repetition duration (contraction duration for each repetition) of resistance exercise on muscle hypertrophy and its underlying mechanisms using a rat exercise model. Male Sprague-Dawley rats were randomly assigned to three groups trained with short (S), medium (M), and long (L) repetition durations. During resistance exercise, the right gastrocnemius muscles were electrically stimulated to induce maximal tetanic contractions, each lasting for 1, 3, and 9 s in S, M, and L groups, respectively. The number of contractions in each set and the interset rest duration were the same across groups, whereas the number of sets was adjusted to match the total torque-time integral of plantar flexion. The left (untrained) and right (trained) gastrocnemius muscles were sampled 48 h after 12 exercise bouts. The average and peak torques during each exercise were consistently highest in S and lowest in L. The muscle mass and fiber cross-sectional area significantly increased in S and M but not in L. The concentrations of total RNA and 18S + 28S rRNA increased only in S and were correlated with muscle mass when the three groups were combined. We also sampled muscle tissues 6 h after a single exercise bout and found no significant difference in muscle protein synthesis, mTOR signaling activity, ribosome biogenesis, or protein degradation between the groups. These results suggest that a long repetition duration does not promote but rather diminishes the hypertrophic effects of resistance exercise, and that acute molecular responses to resistance exercise cannot predict such effects.NEW & NOTEWORTHY Using a rat model, we investigated the hypertrophic effects of resistance exercise with different repetition durations under conditions where the torque-time integrals were matched. The results suggest that exercise with short but not long repetition duration effectively induces muscle hypertrophy. The lack of hypertrophic response or ribosome biogenesis with long repetition duration may not be predicted by acute molecular responses to exercise but may be explained in part by attenuated torque production during exercise.

During spaceflight, humans are exposed to unfamiliar gravitational fields and to rapid transitions in the magnitude of these gravitational fields. Many aspects of sensorimotor neural function are altered by these transitions, and adaptation after transitions has been characterized. However, it is important to know whether human physiology has inherent limitations in hypogravity (i.e., gravity between 0 and 1.0 G) that cannot be overcome by adaptation. To address this critical gap, we studied manual control performance using a laboratory-based centrifuge that was configured and used to mimic hypogravity. Ten healthy human subjects performed a manual control task using a joystick to control the tilt of the motorized chair upon which they were sitting. Manual control performance worsened immediately after transition from 1.0 G_c to 0.5 G_c (69%), partly adapted over 18 min in 0.5 G_c, and remained significantly worse despite adaptation (42%) (1.0 G_c = 9.81 m/s² of centripetal acceleration). We propose that in hypogravity, any particular body tilt will result in diminished shear force on sensory graviceptors relative to 1 G, reducing signal relative to intrinsic neural noise. This necessitates larger tilt angles before manual control inputs can be determined, thus worsening performance. These results add to prior studies providing evidence supporting the hypothesis that closed-loop sensorimotor performance may be fundamentally limited by signal-to-noise ratio, including in hypogravity. This may contribute to risk during lunar piloting and ambulation. We also studied underlying mechanisms using a computational model of closed-loop control and found that adaptation was associated with increasing control gain (K_P).NEW & NOTEWORTHY Prior studies suggest that humans can adapt to hypogravity (i.e., 0-1.0 Earth G). We examined human manual control performance during the transition from an Earth-gravity to a hypogravity condition. We found that performance worsened significantly after the transition. With practice in the hypogravity condition, performance partially improved with practice over repeated trials, but remained impaired in the hypogravity condition relative to the Earth-gravity condition.

Acute intermittent hypoxia (AIH) elicits plasticity in multiple respiratory motor pools and is a promising therapeutic approach to restore breathing ability in individuals with neuromuscular injury/disease. In anesthetized rats, diurnal cycle affects the magnitude and mechanism of moderate AIH (arterial partial pressure of oxygen [Formula: see text] ∼40-50 mmHg) induced phrenic motor plasticity in an AIH protocol-specific manner. However, diurnal cycle and AIH protocol effects on ventilatory long-term facilitation (vLTF) in unanesthetized rats have not been reported. Measurements of vLTF assess the collective physiological impact of plasticity in all respiratory motor pools and control for the effects of anesthesia, paralysis, and vagotomy common in phrenic LTF studies. Using 2 AIH protocols consisting of 15, 1-min (15x1; [Formula: see text] = 0.09) or 3, 5-min (3x5; [Formula: see text] = 0.105) moderate hypoxic episodes, we tested the hypothesis that diurnal cycle regulates AIH-induced vLTF in unanesthetized male Sprague-Dawley rats. Minute ventilation (V̇e), tidal volume (V_T), breathing frequency (f_R), and metabolic CO₂ production (V̇co₂) were assessed via whole-body plethysmography during mid-rest (light) and mid-active (dark) phases. Since V̇e and V_T correlate strongly with V̇co₂ across the rest/active cycle, and AIH decreases V̇co₂, we normalized V̇e and V_T to V̇co₂ (V̇e/V̇co₂ and V_T/V̇co₂) to account for changes in ventilation linked to metabolism. We found that 15x1 AIH elicits greater vLTF in mid-rest, whereas 3x5 AIH is more effective in mid-active phase, indicating that diurnal cycle regulates respiratory motor plasticity in an AIH protocol-specific manner in unanesthetized rats. Diurnal cycle is an important consideration as we translate knowledge based on nocturnal rodents to diurnal humans with neuromuscular injury/disease.NEW & NOTEWORTHY Although acute intermittent hypoxia (AIH) elicits phrenic motor plasticity in a manner influenced by diurnal cycle and the specific AIH protocol used, it is unknown how diurnal cycle and AIH protocol regulate AIH-induced ventilatory long-term facilitation (vLTF) in unanesthetized rodents. We report that shorter hypoxic episodes elicit greater vLTF in mid-rest phase, whereas longer episodes are favorable in mid-active phase. Thus, diurnal cycle and AIH protocol must be considered in studies of respiratory motor plasticity.

This study investigated baroreflex regulation of sympathetic action potential (AP) discharge during large, rapid blood pressure changes caused by ventricular bigeminy and sinus pause in a healthy female participant. Muscle sympathetic APs (microneurography, continuous wavelet transform) and blood pressure (Finometer) were recorded during baseline (BSL; 5-min), cold face challenge (Cold; 0°C cold pack), and a maximal end-inspiratory apnea. Cold face challenge increased sympathetic AP discharge (BSL: 8 APs/burst, Cold: 49 APs/burst) and recruited large APs (BSL: 21 AP clusters, Cold: 27 AP clusters). Ventricular bigeminy occurred during cold face challenge and caused large increases in mean pressure (+16 mmHg). The first bigeminal beat reduced sympathetic AP discharge (bigeminy beat 1: 7 APs/burst) and derecruited large APs (bigeminy beat 1: 4 AP clusters). As bigeminy continued (bigeminy beats 2 and 3) and blood pressure remained high, AP discharge increased (bigeminy beats 2 and 3 average: 43 APs/burst), and large APs were rerecruited (bigeminy beats 2 and 3 average: 18 AP clusters). During bigeminy, sympathetic AP baroreflex functions were reset upward to higher discharge probabilities and rightward to higher blood pressures, indicating rapid baroreflex resetting. Bigeminy also reduced sympathetic AP discharge latency (-0.04 s). During a separate apnea protocol, a 2.4-s sinus pause occurred and caused a large reduction in mean pressure (-15 mmHg) that increased the discharge of medium- and large-sized sympathetic APs. This experiment of nature, enabled by ventricular bigeminy and sinus pause, suggests that the baroreflex governs sympathetic AP discharge, recruitment, and latency during large, rapid blood pressure changes.NEW & NOTEWORTHY Our knowledge regarding human baroreflex regulation of sympathetic action potential (AP) discharge remains incomplete. Cardiac arrhythmias in a healthy female provided a unique opportunity to examine baroreflex regulation of sympathetic AP discharge during large, rapid blood pressure changes. Our novel findings include: 1) rapid baroreflex loading due to ventricular bigeminy reduced AP discharge and derecruited large APs, 2) as bigeminy continued, rapid baroreflex resetting increased AP discharge, and 3) rapid baroreflex loading reduced AP latency.

Vascular endothelial function can be interrogated by imposing blood flow-associated shear stress, which stimulates endothelial-dependent dilation [flow-mediated dilation (FMD)]. A larger FMD response is indicative of better endothelial function. In the well-established technique used to assess human conduit artery endothelial function, a shear stress stimulus is created via the release of temporary limb occlusion, which results in a transient reactive hyperemia (RH; RH-FMD). However, sustained increases in shear stress created with small muscle mass exercise, limb heating or distal vasodilator infusion can also be used to stimulate conduit artery FMD to interrogate endothelial function [sustained stimulus FMD (SS-FMD)]. Cell and animal evidence suggests that endothelial shear stress transduction depends on the duration of the shear stress stimulus such that transient and sustained shear stress exposure recruit distinct signaling pathways. Furthermore, work in humans has demonstrated that RH-FMD and SS-FMD provide unique insight regarding the impact of interventions and clinical conditions on endothelial function. This suggests that testing both RH-FMD and SS-FMD may provide a more comprehensive picture of endothelial function; however, SS-FMD is rarely performed. Here, we describe how SS-FMD can be assessed in the brachial artery using handgrip exercise to achieve either a target shear stress stimulus or an incremental increase in shear stress stimulus.NEW & NOTEWORTHY This article provides the first methodological guide to utilize handgrip exercise for assessment of SS-FMD in the brachial artery in response to targeted steady state and incremental increases in shear stress. SS-FMD is a physiologically relevant response, reflecting conduit artery behavior during sustained exertional activity and can provide distinct information regarding endothelial function compared with reactive hyperemia-FMD.

Although physiological responses during ultra-endurance events are becoming better understood in recreational runners, very little is known about how these responses manifest in elite athletes. This case study reports the physiological, nutritional, and thermoregulatory responses of an elite ultra-endurance athlete who completed the 2025 Western States Endurance Run (WSER 100) in 14:19:22, finishing third overall and within 10 min of the course record. This case study provides the first comprehensive in-race assessment of energy expenditure and intake, hydration, and renal responses in a world-class athlete under competitive race conditions. Measurements included within-event total energy expenditure (doubly labeled water), energy intake, heart rate, gastrointestinal temperature (telemetric ingestible pill), body mass, renal biomarkers [neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1)], and durability assessed from GPS-derived pacing data. Total energy expenditure was 16,104 kcal. Energy intake totaled 6,720 kcal (∼86 g carbohydrate·h^-1). The athlete consumed 12.5 L of fluids (0.87 L·h^-1; 18.5 g sodium) and lost 4.3% body mass. Mean gastrointestinal temperature was 37.1°C and peaked at 39.4°C. Urinary biomarkers showed transient renal stress, with NGAL concentrations increasing from 9.4 to 25.4 ng·mL^-1 and KIM-1 from 0.30 to 1.70 pg·mL^-1, alongside mild proteinuria and hematuria. Pacing analysis showed a mean normalized speed of 84.8% of predicted critical speed, with a 15% decline across the race, demonstrating exceptional fatigue resistance. This case defines the upper range of energy expenditure (∼18.8 kcal·min^-1) and carbohydrate ingestion sustainable in ultra-marathon running.NEW & NOTEWORTHY This case study provides the first comprehensive, in-race assessment of physiological, nutritional, and thermoregulatory responses in a world-class ultra-endurance athlete during the 2025 Western States Endurance Run. Using doubly labeled water, ingestible telemetry, and renal biomarkers, this study quantifies the upper limits of energy expenditure (18.8 kcal·min^-1), carbohydrate intake (86 g·h^-1), and fatigue resistance achievable in competitive ultra-endurance performance under extreme environmental conditions.

Night-shift work is prevalent among healthcare workers and disrupt circadian rhythms, potentially influencing blood pressure (BP) regulation. Pregnancy itself causes significant BP fluctuations, and night shifts may exacerbate these changes, increasing the risk of hypertension disorders. However, studies on the impact of shift work on BP patterns in pregnancy in a free-living environment is currently lacking. We recruited 25 pregnant nurses in their second trimester, comprising 13 on day shifts (DS) and 12 on night shifts (NS), from eight urban hospitals in Edmonton, Alberta, Canada. Resting BP [systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP), and pulse pressure (PP)] was assessed before and after shift work. Data were analyzed to compare pre- and postshift measurements between DS and NS workers using a linear mixed-effects model, with statistical significance set at P < 0.05. NS workers showed significantly higher post-shift DBP and MAP compared with DS workers (P < 0.001). In contrast, NS workers exhibited a significant postshift decrease in pulse pressure (PP) than the DS group (P < 0.001), indicating distinct acute hemodynamic responses to NS work. NS work in pregnant nurses is associated with acute elevations in DBP and MAP, along with a significant reduction in PP following the shift. These findings suggest that NS may trigger distinct hemodynamic stress responses during pregnancy, potentially increasing short-term cardiovascular load.NEW & NOTEWORTHY Night shift work in pregnant nurses is associated with acute elevations in diastolic and mean arterial pressure, along with a significant reduction in pulse pressure following the shift. These findings suggest that night shifts may trigger distinct hemodynamic stress responses during pregnancy, potentially increasing short-term cardiovascular load.

Muscle protein metabolism is thought to regulate muscle mass. High-intensity muscle contraction (HiMC) increases muscle protein synthesis (MPS), resulting in muscle hypertrophy. Inhibiting the mechanistic target of rapamycin complex 1 (mTORC1) using rapamycin leads to partially inhibited mTORC1 activation, along with increased MPS, and muscle hypertrophy after HiMC. Therefore, we hypothesized that rapamycin-sensitive mTORC1 regulates myofibrillar protein translation, and the purpose of this study was to investigate this possibility. The right gastrocnemius muscle of male Sprague Dawley rats was contracted isometrically via percutaneous electrical stimulation, and the left gastrocnemius muscle served as control. Vehicle or rapamycin was intraperitoneally injected 1 h before HiMC. Gastrocnemius muscles were collected at 6 h after a bout of HiMC and 48 h after chronic muscle contractions for 4 wk (3 HiMC per week). Rapamycin completely inhibited HiMC-induced activation of 70 kDa ribosomal protein S6 kinase, which is a rapamycin-sensitive mTORC1 substrate. However, rapamycin completely inhibited HiMC-induced dissociation of eukaryotic translation initiation factor 4E (eIF4E):eukaryotic translation initiation factor 4E (eIF4E)-binding protein (4E-BP1) and the interaction of eIF4E:eIF4G, despite the HiMC-induced phosphorylation of 4E-BP1 (Thr37/46, Thr70, and Ser65) being unaffected by rapamycin. Importantly, HiMC-induced myofibrillar protein synthesis was not influenced by rapamycin. Changes in myosin and actin levels relative to muscle mass induced by chronic muscle contraction remained constant even under rapamycin administration. These results indicated that rapamycin-sensitive mTORC1 signaling is not fully responsible for contraction-induced increases in myofibrillar protein synthesis.NEW & NOTEWORTHY Muscle contraction activates mTOR signaling, resulting in increased protein synthesis and muscle hypertrophy. Rapamycin-sensitive mTORC1 is important for cap-dependent translation, but the effects of suppressing mTORC1 function using rapamycin on myofibrillar protein synthesis caused by contraction remains unclear. We observed that the eIF4F complex is a translation initiator induced by contraction dependently on rapamycin-sensitive mTORC1. Myofibrillar protein translation increased by muscle contraction was insensitive to rapamycin.