Journal of applied physiology最新文献

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.

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.

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.

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.

Idiopathic hyperventilation syndrome (HVS) is a poorly understood condition with potential mechanisms involving altered CO₂ chemosensitivity, CO₂ store depletion, and reduced plant gain (PG). Twelve carefully selected patients with HVS (HVS+), diagnosed by symptoms, normal lung function, and a positive hyperventilation provocation test, were compared to 12 matched healthy controls (HVS-). All participants underwent a hypercapnic-hyperoxic challenge test (HHCT), assessing ventilatory and drive-to-breathe responses and dyspnea. Parameters included controller gain (β-slope), ventilatory and drive recruitment thresholds (VRT and DRT), extrapolated apneic and chemoreflex thresholds (AT and CT), CO₂ stores, PG, and peripheral sensitivity range (PSR = VRT-AT). Compared to HVS-, patients with HVS+ showed elevated baseline ventilation, ventilatory variability, drive-to-breathe, and dyspnea (all P ≤ 0.048). During HHCT, despite a similar β-slope, HVS+ exhibited a leftward-shifted ventilatory response curve, with lower AT and CT, expanded PSR, and reduced PG (all P ≤ 0.021), suggesting reduced CO₂ buffering and heightened peripheral chemosensitivity. While in HVS- baseline breathing patterns correlated closely with end-tidal CO₂ pressure and VRT, in HVS+ the ventilation magnitude and variability were associated with PG, PSR, and CO₂ stores (all P ≤ 0.048). Multivariate regression showed that PG was predicted by PSR, CO₂ stores, and their interaction. PG and ventilatory variability emerged as strong predictors of HVS+. These findings reveal a distinct ventilatory phenotype in HVS+ marked by increased reliance on peripheral chemoreflex inputs and disrupted CO₂ buffering capacity. PG and ventilatory variability emerged as strong predictors of HVS+ status, reinforcing their potential diagnostic value. These results support a novel pathophysiological model that warrants further investigation.NEW & NOTEWORTHY Patients with idiopathic hyperventilation syndrome (HVS) displayed preserved central chemosensitivity but altered ventilatory control at rest, characterized by elevated ventilation, increased variability, and a leftward-shifted hypercapnic response. These features were strongly associated with peripheral chemosensitivity, CO₂ stores, and reduced plant gain, patterns not observed in controls. These findings support a novel integrative model in which altered CO₂ buffering and peripheral afferent inputs, rather than central mechanisms alone, contribute to ventilatory instability in HVS.

In very preterm infants, nonuniform lung aeration occurs when regions of the immature lung remain liquid-filled after birth, which restricts gas exchange to aerated lung regions. We have examined the effect of surfactant administration on the uniformity of lung aeration and the distribution of ventilation in mechanically ventilated preterm rabbits. Preterm kittens (28-29 days gestation; term: ∼32 days) were delivered by cesarean section and intubated via tracheostomy. Before the experiment, kittens were initially ventilated (intermittent positive pressure ventilation; iPPV) to achieve whole (both lungs) or partial (one lung) lung aeration. Kittens were then ventilated (volume targeted: 8 mL/kg) with or without an initial sustained inflation (SI), before surfactant. Lung aeration was measured before and after surfactant, using phase contrast X-ray imaging and plethysmography. iPPV alone was unable to aerate unaerated lung regions, resulting in regional overexpansion due to a marked nonuniform distribution of ventilation. Although a SI increased aeration of nonaerated lung regions, the effect of surfactant was markedly greater, resulting in aeration of previously unaerated lung regions and markedly reducing regional overexpansion. Surfactant administration soon after birth greatly increases the uniformity of lung aeration and distribution of ventilation in mechanically ventilated very preterm newborns.NEW & NOTEWORTHY Preterm newborns commonly receive intermittent positive pressure ventilation (iPPV) at birth, but the optimal approach that facilitates uniform lung aeration is unknown, particularly in a partially aerated lung. We have shown that surfactant administration to partially aerated lungs markedly enhances aeration of unaerated lung regions, which redistributes the incoming tidal volume to more evenly ventilate the lung. These experimental findings support the rationale to administer surfactant as soon as possible after birth in preterm infants.

This study examined the effect of the knee-joint angle on motor unit (MU) discharge properties of the vastii muscles and their modulation with contraction level. Twelve young adults performed unilateral isometric knee-extension contractions during three experimental sessions at either 25°, 55°, and 85° of knee flexion (full extension: 0°) in a randomized order. Each session involved maximal voluntary contractions (MVCs) followed by submaximal trapezoidal and triangular contractions at different levels relative to maximal voluntary torque (MVT). High-density surface electromyograms were recorded from vastus lateralis and medialis muscles and, subsequently, decomposed to obtain discharge timings of individual MUs. MVT was the greatest, whereas MU discharge rate (DR) during MVCs and submaximal contraction levels (≥30% MVT) was the lowest at the intermediate joint angle (55°). The highest DR during MVCs and high-level contractions (70% MVT), however, was at the most flexed knee position (85°), which was due to a greater DR increase 50%-70% MVT compared with 25° and 55°. The onset-offset DR hysteresis (ΔF), an estimate of persistent inward current contribution to motoneuron discharge, decreased with knee flexion and increased with contraction level, whereas the degree of motoneuron input-output nonlinearity (brace height) did not vary with joint angle but decreased with contraction level. At 85°, ΔF increased more and brace height decreased less with contraction level compared with 25° and 55°. These findings indicate that vastii MU DR and its modulation with contraction level vary with knee-joint angle, which could be partly explained by the modulation of motoneuron intrinsic electrical properties.NEW & NOTEWORTHY This study explored the relationship between motoneuron output to the vastii muscles at different knee-joint angles (quadriceps lengths) and isometric contraction levels. We showed that the motor unit discharge rate was lowest at the angle of the greatest absolute torque capacity, whereas the contraction-level-induced increases in discharge rate and motoneuron excitability were the greatest in the flexed position. These findings suggest that joint-angle-dependent adjustments in sensory feedback modulate motor control of the knee-extensor muscles.

Even brief periods of physical inactivity can induce metabolic disruptions; however, the underlying cellular and molecular mechanisms initiating these alterations remain unclear. We investigated whole-body and skeletal muscle-specific metabolic responses to short-term inactivity induced by dry immersion (DI), a model of rapid physical deconditioning. Eighteen healthy men (age = 33.6 [SD 5.5] years, body mass index (BMI) = 23.3 [1.8] kg/m²) underwent five days of DI in a longitudinal within-subject design, with each participant serving as his own control. DI-induced inactivity reduced V̇o_2max (-7.4%, P = 0.003), fat mass [dual energy X-ray absorptiometry (DXA), -2.6%, P = 0.002], fat-free mass (DXA, -2.6%, P < 0.001), and quadriceps cross-sectional area (MRI, -2.8%, P < 0.001). Fat content increased in the liver (MRI, +21%, P < 0.001), but not in the muscles (MRI, +0.1%, P = 0.218). Urinary nitrogen excretion rose (+28%, P < 0.001), indicating increased whole-body protein catabolism. Fasting insulin (+46%, P = 0.009) and triglycerides (+14%, P = 0.013), as well as postprandial incremental glucose (+49%, P = 0.002) and insulin (+90%, P < 0.001) concentrations following a carbohydrate-rich meal were increased. Fasting and postprandial total lipid and carbohydrate oxidation measured by indirect calorimetry and adjusted for body composition remained unchanged (P > 0.05 for all). In differentiated myotubes isolated from vastus lateralis biopsies, insulin-stimulated Akt Thr308 phosphorylation (P = 0.03), in vitro glycogen synthesis assessed from U-¹⁴C glucose (P < 0.01), and the ability to suppress in vitro palmitate oxidation (1-¹⁴Cpalmitate) following incremental glucose concentrations were impaired (P = 0.02). The ability to increase palmitate oxidation when palmitate availability rises was not significantly altered. These results suggest that early intrinsic skeletal muscle cell changes may contribute to the onset of whole-body metabolic disorders induced by physical inactivity.NEW & NOTEWORTHY Five days of dry immersion led to reduced cardiovascular fitness, muscle atrophy, hepatic fat accumulation, and lower glucose tolerance. These alterations occur despite no detectable changes in whole body fat and carbohydrate oxidation following a carbohydrate-rich meal. In cultured primary myotubes, insulin action and metabolic flexibility (fuel switching) are impaired. Early alterations in intrinsic muscle cell metabolism likely reflect rapid epigenetic imprinting of satellite cells and may contribute to systemic metabolic disturbances induced by physical inactivity.