Journal of applied physiology最新文献

This study tested the hypothesis that the critical cold-water temperature (T_crit) at which core temperature can no longer be maintained while wearing an approved wetsuit is below the currently mandated water temperature of 16°C. We further aimed to examine the effect of wetsuit sleeves on T_crit. We recruited 20 trained swimmers (12 men, 8 women) who completed 120-min progressive cooling swim trials in a swim flume. Water temperature at the start was 16°C and decreased ∼0.15°C every 10 min while swimming at race-representative intensity and wearing a full-length wetsuit. A subset (n = 8) completed an additional swim trial comparing sleeved versus sleeveless wetsuits. The water temperature upon which core temperature could not be maintained (i.e., T_crit) was identified using segmental linear regression. Median T_crit was 15.0°C [95% confidence interval (CI): 14.8-15.3°C], significantly below the 16°C regulation (P < 0.001). No differences in T_crit were observed between genders [P = 0.78; men: 15.0°C (95% CI: 14.6-15.3°C); women: 14.91°C (95% CI: 14.6-15.4°C)] or wetsuit types (P = 0.90; sleeved: 15.1 ± 0.5°C; sleeveless: 15.1 ± 0.6°C). Multiple regression analysis revealed that body fat percentage (β-coefficient: -0.06088: P = 0.0390), metabolic heat production (β-coefficient: -0.004416; P = 0.0079), and body surface area-to-mass ratio (β-coefficient: -370.6; P = 0.0078) significantly explained T_crit (R² = 0.41, P = 0.008). Although our data demonstrate that trained swimmers can physiologically tolerate temperatures below current regulations, we recommend maintaining the 16°C mandate to provide appropriate safety margins for the diverse competitive population and variable real-world conditions encountered in open water swimming competitions.NEW & NOTEWORTHY Using a novel experimental protocol, this study provides empirical determination of critical cold-water temperature for competitive open water swimmers while wearing two different World Aquatics-approved wetsuits designs. Well-trained swimmers protected core temperature down to 15.0°C, below current 16°C regulations, which did not differ between sleeved and sleeveless wetsuits. These findings provide objective evidence supporting current conservative regulatory approaches.

Neurological injury, the leading cause of death after cardiac arrest resuscitation, has been shown to worsen progressively in the postcardiac 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 postcardiac arrest period. Rats were anesthetized, intubated, catheterized, and randomized into a sham group or cardiac arrest group. Cardiac arrest rats underwent 7 min of cardiac arrest. Subsequently, groups were observed for 4 h. Middle cerebral arteries (MCAs) were examined using pressure myography and confocal microscopy. qPCR was performed on the posterior communicating arteries. 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 with 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 nitric oxide 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. In rat MCAs, the myogenic response, myogenic tone, and the maximum contraction are significantly reduced 4 h after cardiac arrest. Our results suggest impaired calcium-sensitizing mechanisms in cerebral myogenic vasoconstriction after cardiac arrest.NEW & NOTEWORTHY Cerebral autoregulation is impaired in the postcardiac arrest period, potentially altering cerebral blood flow and exacerbating neurological injury after resuscitation. To our knowledge, the current study is the first to demonstrate that cerebral arteries exhibit reduced myogenic response, tone, and contractility in an animal model following resuscitation from cardiac arrest. These alterations in vasoreactivity appear to result, at least in part, from decreased calcium sensitivity in cerebral vascular smooth muscle cells.

Acute hypobaric hypoxia induces rapid neurovascular adjustments in the central nervous system, yet the specific spatiotemporal dynamics of these responses remain incompletely understood. The retina, with its high metabolic demand and direct accessibility, provides a unique noninvasive model to investigate neurovascular coupling dynamics under simulated high-altitude hypoxia. Twenty-one healthy adults underwent ophthalmic evaluations at sea level, during a stepwise ascent to 4,500 m in a hypobaric chamber (simulated altitudes: 3,500 m, 4,000 m, 4,500 m), and during a subsequent recovery phase. Images were acquired 10 min after reaching each plateau. Optical coherence tomography angiography (OCTA) was used to quantify vessel density (VD), perfusion area (PA), and small-vessel density (SVD). Full-field electroretinogram (ERG) was recorded under dark- and light-adapted conditions. Linear mixed-effects models and correlation analyses were used to assess altitude-related changes. The superficial vascular plexus (SVP) exhibited a sustained compensatory vasodilation (increased VD and PA) across all altitudes. In contrast, ERG amplitudes declined significantly at 4,500 m, revealing a functional supply-demand mismatch. Strict statistical analysis revealed a loss of linear neurovascular correlation during hypoxia, while strong correlations re-emerged during the recovery-phase. In addition, physiological parameters did not immediately return to baseline during recovery, indicating a distinct physiological hysteresis. The retina displays differential neurovascular responses during progressive hypoxia. Although the superficial microvasculature mounts a sustained compensatory response, neuronal function decompensates under severe stress. These results suggest that retinal vascular dilation reaches a functional ceiling, leading to neurovascular uncoupling, and that the system exhibits a metabolic lag during recovery.NEW & NOTEWORTHY This study identifies a critical "functional mismatch" in retinal neurovascular adaptation to acute hypoxia. We demonstrate that while superficial microvasculature sustains compensatory dilation up to simulated 4,500 m, neuronal function significantly declines. This dissociation suggests that vascular autoregulation reaches a functional ceiling, failing to sustain neural activity under severe stress. These findings establish the retina as a sensitive noninvasive model for determining the physiological limits of cerebral oxygen regulation.

Low-dose carbon dioxide (CO₂) can stabilize ventilatory drive, reduce sleep-disordered breathing, and improve sleep quality. However, the existing delivery systems introduce dead space and resistance that limit tolerability. We developed a novel mask with low resistance and minimal dead space to deliver CO₂ and evaluated its overnight effects on neural respiratory drive, sleep architecture, and potential CO₂ accumulation in healthy individuals. Sixteen healthy volunteers [age 42 ± 15 yr; body mass index (BMI) 22.0 ± 2.3 kg/m²] first underwent polysomnography with diaphragmatic electromyography (EMG) recorded via esophageal electrodes under inhalation of different concentrations of CO₂. Participants then completed four consecutive overnight polysomnography sessions, with each night involving inhalation of a different CO₂ concentration (0.0%, 2.5%, 3.5%, or 5.0%) in randomized order. Arterial blood gases were sampled in the evening before inhalation and the following morning during CO₂ exposure. Overnight urinary catecholamines were also measured. Neural respiratory drive increased dose-dependently. Sleep efficiency was highest at 2.5% CO₂ (91.7 ± 5.7%) and lowest at 5.0% (78.5 ± 10.1%, P < 0.001); 3.5% CO₂ showed sleep efficiency similar to room air, whereas 5.0% reduced rapid eye movement (REM) sleep and increased arousals. Blood gases, blood pressure, heart rate, and catecholamines remained normal at ≤3.5%. Baseline blood gases remained normal after multiple consecutive nights of CO₂ inhalation. Overnight inhalation of 2.5% CO₂ delivered via the special mask enhances sleep efficiency without adverse physiological effects. Concentrations ≤3.5% appear safe, and no cumulative effect was observed after multiple consecutive nights of CO₂ inhalation in healthy subjects.NEW & NOTEWORTHY A novel low-resistance open-mask system enables safe delivery of low-dose CO₂ during sleep. Inhaling 2.5% CO₂ improves sleep efficiency and increases N3 sleep in healthy adults, without CO₂ retention or physiological stress. CO₂ up to 3.5% was safe and well tolerated and showed no cumulative effects. These findings demonstrate the physiological safety of low-dose CO₂ during sleep and support its potential for treating hypocapnia-related central sleep apnea.

Cardiopulmonary exercise testing (CPET) is frequently requested in the hope that detecting the maximal limits of cardiovascular or respiratory function will provide clinically relevant information on the genesis of exertional dyspnea. We provide a concise review of emerging evidence that analyzing whole test data, accounting for the dynamic (mis)match between requirements and capabilities (i.e., progressive reserve depletion), is more accurate and valuable for clinical decision-making than the traditional respiratory limitation paradigm. In this context, a pattern of excessive breathing emerges when heightened inspiratory muscle activation is fully translated into increased ventilation in the absence of mechanical restraints, such as reduced [Formula: see text], increased physiological dead space, or high CO₂ output. Conversely, constrained breathing results from impediments to tidal volume expansion, imposed by the prevailing inspiratory capacity, which hinders ventilation despite increased inspiratory muscle activation. Based on sex- and age-adjusted standards for submaximal 0-10 Borg dyspnea-work rate and dyspnea-ventilation, dynamic ventilatory reserve-work rate, and dynamic inspiratory reserve-ventilation, the practitioner can readily identify whether excessive and/or constrained breathing can explain the subject's exertional dyspnea. Regardless of the precise mechanism of excessive breathing, therapeutic efforts should primarily focus on reducing the sources of increased afferent ventilatory stimuli. The identification of constrained breathing should prompt interventions to improve inspiratory reserve volume. This pragmatic approach to clinical CPET interpretation focuses on dyspnea as a treatable trait across physiological and disease states, aiming at providing cogent explanations for the symptom in light of the pretest likelihood of abnormality.

Women with a history of preeclampsia (hxPE) show reduced executive function (EF) and processing speed (PS) compared with a healthy pregnancy (HP). Central (carotid) artery pulsatile pressure hemodynamics and stiffness are associated with reduced cognitive function with aging, but it is unknown if this relation exists in women with a hxPE. We hypothesized that higher carotid artery pulsatile pressure hemodynamics and stiffness would mediate reductions in cognitive function among women with a hxPE. Carotid artery applanation tonometry, B-mode ultrasonography, and wave separation analysis were used in 121 postpartum women (9 mo-5 yr after delivery, aged 18-45 yr; n = 59 hxPE and n = 62 HP) to calculate forward and backward pressure wave amplitudes, and pulse pressure (PP). Carotid stiffness components were derived by participant-specific exponential modeling. EF and PS were represented as Z-scores. Mediation analysis determined the contribution of carotid outcomes in association between preeclampsia status and cognitive function. Women with a hxPE had higher carotid Pb, PP, and load-dependent stiffness compared with those with HP (body mass index and age adjusted, P = 0.009, P = 0.005, and P < 0.001, respectively). After education and age adjustment, the hxPE group had significantly lower PS compared with HP (P = 0.009); executive function was not different (P = 0.08). No pulsatile pressure hemodynamic or stiffness factor mediated associations between preeclampsia status and PS (all P > 0.05). Women with a hxPE have greater carotid PP, Pb, and load-dependent stiffness, compared with a HP. Neither carotid artery pulsatile pressure hemodynamics or load-dependent stiffness mediated lower PS among women with a hxPE.NEW & NOTEWORTHY The novel finding is that higher carotid artery pulsatile pressure hemodynamics and load-dependent stiffness do not mediate reduced processing speed performance in young women with a history of preeclampsia. No difference was seen in EF between groups when adjusted for education and age. These findings clarify the contribution of pulsatile pressure hemodynamics to cardiovascular disease risk and highlight the need for future research on cognitive performance in women with a history of preeclampsia.

The ability to endure psychosocial stressors is critical for mental and physical well-being. Clarifying mechanisms that differentiate high- from low-tolerant individuals may inform resilience-oriented interventions. This exploratory study aimed to predict tolerance to the socially evaluated cold pressor test (SECPT) from a multimodal set of psychological ratings and physiological markers, quantifying how psychophysiological responses account for individual differences in acute psychosocial stress tolerance. Thirty healthy adults completed a 5-min baseline followed by the SECPT. Self-reported perceptual and affective responses, electrodermal activity, and electroencephalography [EEG; sensor-level Granger connectivity computed over a frontoparietal (FPN) scalp montage] were acquired throughout; a brief semi-structured interview complemented quantitative findings. Models were evaluated with stratified fivefold cross-validation. A random forest regressor with a square-root-transformed duration target explained 23.5% of the variance. Two composite features emerged as primary, directionally opposite predictors: the stress response index showed a positive effect; higher perceived stress, arousal, and pain were associated with longer tolerance, whereas FPN causal connectivity showed a negative effect; stronger directed influence predicted shorter tolerance. The SECPT manipulation produced a perceptual profile of higher stress, pain, and arousal with lower affective valence and perceived dominance. Sympathetic activity predominated, with an early peak and a trend toward habituation. Global FPN connectivity was attenuated, most notably over parietal, central-parietal, and frontal interhemispheric circuits. Together, these results indicate that tolerance reflects an interplay between subjective reactivity and network control dynamics. The findings provide initial, mechanistically informed markers of psychosocial stress tolerance and motivate larger studies to test generalizability and temporal dynamics.NEW & NOTEWORTHY We integrated self-report, electrodermal activity, and EEG connectivity focused on the frontoparietal network (FPN) to predict psychosocial stress tolerance. A random forest model explained 23.5% of the variance. Two composites showed opposing effects: a higher stress response index predicted longer tolerance, whereas a stronger FPN causal connectivity predicted shorter tolerance. SECPT produced sympathetic-dominant arousal and attenuated global FPN connectivity. Findings provide insights into the mechanisms underlying stress tolerance in psychosocial contexts.

Marathon and ultramarathon runners commonly exhibit postrace rises in biomarkers of acute kidney injury. Although these perturbations are generally transient and resolve without treatment, rare but serious cases of clinically significant kidney injury in endurance athletes have been documented postrace. The purpose of this mini-review is to discuss the recent literature demonstrating a link between prolonged endurance running and acute kidney injury risk. We present the following: 1) the primary mechanisms by which endurance exercise contributes to acute kidney injury; 2) factors that may modulate kidney injury risk in endurance athletes; 3) recommendations and considerations for field-based studies; and 4) clinical implications and event-specific considerations. In brief, hemodynamic, muscular, gastrointestinal, and hydration stressors collectively contribute to increased risk for acute kidney injury during prolonged endurance running. In addition, there are several extrinsic (e.g., net elevation, temperature, humidity), intrinsic (e.g., biological sex, age, fitness), and behavioral (e.g., event hydration practices, training status) factors that likely contribute to the heterogeneous responses observed in athletes. Field studies offer unique ecological insight but introduce logistical challenges that are far less controlled than laboratory environments and therefore require important methodological considerations. Longitudinal studies are needed to determine whether repeated episodes of subclinical kidney stress contribute to any long-term decline in kidney function in habitual endurance runners or athletes.

This study compared neuromuscular fatigue induced by an acute wide-pulse high-frequency session, either applied in an isometric condition (WPHF) or combined with muscle lengthening (WPHF + LEN). Fifteen participants completed two randomized sessions, which involved 30 stimulation trains (pulse duration: 1 ms; frequency: 100 Hz; duty cycle: 15 s ON/15 s OFF) applied to the posterior tibial nerve at low stimulation intensity [5%-10% maximal voluntary contraction (MVC)]. In the WPHF session, the ankle joint was held at a reference angle (90°), whereas a 10° muscle lengthening was superimposed during the stimulation in the WPHF + LEN session. Before and after each session, MVC was measured along with neural [voluntary activation level (VAL)] and muscular [potentiated twitch (Pt)] changes. Torque-time integral (TTI) was recorded for each train, and the total TTI (∑TTI) was calculated. Results showed a comparable decrease in MVC torque after the two sessions (-7.8 ± 6.9% for WPHF and -9.4 ± 5.7% for WPHF + LEN, P < 0.001) associated with a significant reduction in Pt amplitude (P < 0.001), indicating muscular changes, whereas VAL remained unchanged. ∑TTI was not different between sessions (9,600 Nm·s for WPHF; 9,550 Nm·s for WPHF + LEN; P = 0.95). However, although TTI significantly decreased throughout the WPHF session, it was preserved during the WPHF + LEN session. These findings indicate a similar amount of neuromuscular fatigue after the two sessions, primarily attributed to muscular alterations. Nevertheless, the combination of WPHF stimulation with muscle lengthening appears advantageous for preserving torque production throughout the stimulation trains.NEW & NOTEWORTHY Results of the present study indicate that a single session of WPHF stimulation modality either applied alone or with muscle lengthening induces the same level of neuromuscular fatigue. Despite no significant difference in total evoked torque between sessions, the present findings highlight potential advantages of superimposing muscle lengthening to preserve torque production during repeated WPHF trains.

Direct recordings from human motoneurons are not feasible; therefore, researchers have developed indirect methods to estimate postsynaptic potential profiles, that is, the functional inhibition or excitation, on firing motor units. Surface and intramuscular electromyography have shown that the duration of the functional inhibition varies depending on the neural circuit investigated and is influenced by stimulus intensity and muscle activity level. This study aimed to standardize the estimation of functional inhibition durations across three distinct spinal and brainstem circuits by leveraging the known dependence of inhibition duration on background motor unit discharge rate. We analyzed data from previous rat brain slice experiments in which known currents were injected into regularly discharging motoneurons. Regression of injected inhibition duration against discharge rate revealed a strong predictive relationship when extrapolated, accurately converging on the known duration. Specifically, this regression yielded the actual inhibition duration at a discharge rate of 0.98 imp/s (range: 0-5.91 imp/s). Building on these findings, we conducted three inhibition paradigms in human volunteers, targeting the masseter inhibitory reflex, the cutaneous silent period and recurrent inhibition mediated by Renshaw cells. Using extrapolated correlation plots of motor unit discharge rate versus functional inhibition duration, we derived discharge rate-independent inhibition durations. All three circuits demonstrated longer inhibition duration ranges than previously reported. This standardized approach enables more accurate estimation of inhibition duration across various circuits, independent of discharge rate. It holds promise for clinical applications in the early diagnosis and monitoring of neurological disorders affecting inhibitory circuits.NEW & NOTEWORTHY Direct recordings from human motoneurons are not feasible; therefore, synaptic inhibition must be estimated indirectly. Experiments on rat brain slices allow accurate prediction of inhibition duration, independent of motor unit discharge rate. Applying these predictions in human studies has revealed discharge rate-independent functional inhibitions across various brainstem and spinal circuits. This approach offers robust estimates of functional inhibition, with potential clinical applications for monitoring neurological disorders that affect neural circuits.