Journal of applied physiology最新文献

Smooth muscle (SM) exhibits rapid mechanical adaptation in response to various stimuli, posing challenges for reproducible experimental results and consistent material parameter determination in biomechanical modeling. Preconditioning involving repeated loading and unloading cycles are commonly used to stabilize mechanical responses prior to testing. However, their influence on tissue properties and data variability remains underexplored. This study compares the effects of three preconditioning routines - passive cycling (PCYC), no preconditioning (PNPC), and free contraction (PFC) - on the active and passive force responses of porcine urinary bladder (UB) SM tissue. Three tissue strips from 12 UBs were randomly assigned to one of the routines and underwent an identical protocol involving a passive stretch ramp and two isometric contractions (IC1, IC2) to evaluate active and passive force development. After PCYC, the tissue generated the highest active (IC2: 44.7 ± 29.4 kPa) and passive tensions (IC2: 5.6 ± 4.3 kPa), though it also showed the highest variance in active tension. PNPC resulted in the lowest variance in active tension with a coefficient of variation (CV) of 45%, and PFC showed the lowest variance in passive tension, CV = 57%. These findings imply that the decision for a certain preconditioning protocol influences the observed mechanical properties. In this context, PFC appears promising for minimizing passive force variability and preventing creep-induced lengthening. This could offer a more reliable foundation for subsequent experiments analyzing mechanical parameters. This study underscores the importance of customized preconditioning strategies to enhance consistency and comparability in SM research and organ modeling.

Low-intensity endurance training with blood flow restriction (BFR) elicits greater improvements in V̇O₂max compared to volume-matched training. However, determinants of V̇O₂max, such as oxygen-carrying capacity and mitochondrial content, do not exhibit proportional improvement. Despite the hemodynamic alterations during BFR exercise that could stimulate remodeling, cardiac adaptations remain unexplored. We assessed cardiac function in athletes (11M/5F) at rest, during semi-recumbent cycling with BFR, and at a matched work and heart rate (HR) using echocardiography. In an exploratory analysis, a subset of athletes (5M/2F) then completed 6 weeks of low-intensity BFR walking 3x/week and echocardiograms were repeated. Compared to rest and unoccluded exercise, BFR increased arterial elastance (Rest: 1.07±0.32mmHg/mL, BFR: 1.32±0.33mmHg/mL, Work-Match: 0.93±0.25mmHg/mL, HR-Match: 0.97±0.25mmHg/mL;all p<0.01) and altered left ventricular (LV) filling, with a greater proportion of filling achieved through atrial contraction (Rest: 45±8%, BFR: 56±8%, Work-Match: 49±6%, HR-Match: 46 ± 7%;all p<0.05) to maintain end-diastolic volume (Rest:163±40mL, BFR: 163±40mL vs. Work-Match: 167±37mL, HR-Match: 168±38mL;p=0.5). Concurrently, stroke volume was reduced (Rest: 99±26mL, BFR:95±23mL, Work-Match:109±27mL, HR-Match:110±25mL;p<0.05) and HR was elevated (Rest: 54±10bpm, BFR and HR-Match:87±13bpm vs Work-Match: 74±11bpm,p<0.01) to maintain cardiac output (Rest: 5.1±1.2L/min, BFR:7.5±1.0L/min, Work-Match: 8.0±1.2L/min, HR-Match: 9.1±1.7L/min;p<0.0001). BFR training did not affect LV mass index (Pre:121±18g/m², Post:123±11g/m²;p=0.5), nor LV function at rest or during unoccluded exercise. However, post-training, stroke volume during BFR exercise was increased (Pre:101±25mL, Post:113±23mL;p=0.03), suggesting adaptation of the cardiac response to this specific stress. This highlights how the heart supports oxygen delivery during BFR exercise and provides insight into how cardiac adaptations may contribute to BFR training-associated improvements in V̇O₂max.

Intensive exercise and high-altitude exposure can disrupt neural activity and impair cognitive functioning. Previous research suggests that ketone ester (KE) ingestion may counteract cognitive impairments, however, its impact on neural activity during exercise and hypoxia remains unclear. Therefore, we investigated the impact of KE on electroencephalography (EEG) patterns and cognition during hypoxia and exercise. Twelve healthy males completed three randomized crossover sessions: i) normoxia + placebo, ii) hypoxia + placebo, and iii) hypoxia + KE. Each session included normoxic endurance (ET_120') and high-intensity interval training (HIIT_80'), followed by a 16-h period including sleep in either normoxia or hypoxia. The next day, participants performed a normoxic 30-min all-out time-trial (TT_30'). EEG was recorded during rest and exercise, while cerebral tissue oxygenation index (cTOI) and cognitive performance were evaluated during rest. At rest, KE attenuated hypoxia-induced increases in alpha and beta power and cTOI declines. Nonetheless, cognitive performance remained unaffected. Brain activity rose throughout ET_120' and normalized during recovery, while HIIT_80' elicited a fluctuating neural response but normalized during recovery. Following TT_30', theta, alpha, and gamma power remained elevated during recovery. Altogether, these data, obtained in healthy males, show the potential of KE to stabilize resting-state EEG patterns in hypoxia. Moreover, they shed light on how EEG patterns vary with exercise intensity, with sustained post-exercise increases in theta, alpha, and gamma power following high-intensity efforts. These findings suggest that KE can help to preserve neural stability under hypoxia and highlight EEG's potential for monitoring fatigue and tailoring training or recovery strategies.

Weightlessness (0.00-G) and partial gravity exposures may contribute to internal jugular vein (IJV) distension and altered cerebral hemodynamics, which may increase the risk of venous thrombosis. Nine participants were studied supine and seated in normal gravity and during parabolic flight while seated. Participants were exposed to 10 parabolas at each G-level: 0.00-, 0.25-, 0.50-, and 0.75-G. Bilateral IJV cross-sectional area (CSA), pressure, and flow were assessed using 2D and Doppler ultrasound. Compared to seated preflight, left IJV CSA increased during 0.00-, 0.25-, and 0.50-G, and right IJV CSA increased during 0.00- and 0.25-G exposures (P<.05). IJV CSA was not significantly different between preflight supine and seated 0.00-G. Left IJV pressure during all reduced G-levels and right IJV pressure during 0.00- and 0.50-G were significantly greater than preflight seated. Normal forward flow was observed in the right and left IJV in all participants preflight and in the right IJV during all G-levels. In 7 of 9 participants the left IJV presented with normal flow across partial-G levels and weightlessness. Stagnant flow was observed in the left IJV during 0.00-G in two participants and during 0.25- and 0.50-G in one participant. Together these data reveal a graded effect in the left and right IJV CSA and pressure across increasing G-levels and normal forward flow in most individuals. Venous stasis developed in the left IJV during acute reduced gravity exposures in 2 participants, suggesting that astronauts should be monitored for flow abnormalities early in their mission and while on the moon and Mars.

Endurance performance exhibits time-of-day variation in both humans and rodents, peaking in the late active-phase. However, whether the timing of endurance training influences performance adaptations remains unclear. To investigate, female mice were trained 5-d/week for 6-weeks at either ZT13 or ZT22, using treadmill running at 70% of each animal's maximal capacity. Endurance performance was assessed at baseline, week-3, and week-6. Secondary outcomes included blood glucose and lactate, cage activity, body composition, liver and skeletal muscle glycogen content, mitochondrial and contractile protein expression. At baseline, late-active phase (ZT22)-tested mice exhibited significantly higher endurance capacity than early-active phase (ZT13)-tested mice (P<0.05). Following 6 weeks of training, ZT13-trained mice demonstrated a greater rate of improvement, with endurance increasing by 132% (P<0.05), compared to 45% in afternoon ZT22-trained mice. By week 6, performance improved but was similar between groups (P>0.05), despite lower absolute training volumes in the ZT13 group. Both training groups reduced fat-mass (ZT13: -31%,ZT22: -32%; P<0.05 vs. control), with no differences in lean mass, food intake or muscle and liver glycogen content (P>0.05). In skeletal muscle, ZT13-trained mice were associated with increased (P<0.05) COXIV protein expression, citrate synthase activity, and shifts in MyHC isoform expression, without changes (P>0.05) in mitochondrial content. ZT13-training elicited superior performance adaptations despite lower absolute workloads, indicating enhanced training efficiency. These findings identify exercise timing as a biologically relevant factor influencing endurance adaptation and variability in exercise responses.

Blood flow restriction (BFR) allows exercise at a lower external load with similar or greater improvements compared with traditional training in nontrained individuals. However, the effect in well-trained competitive athletes is unclear. The aim of this study was to compare effort-matched high-intensity interval training (HIIT) microcycles performed with or without BFR on endurance performance and muscular adaptations in well-trained cyclists. Seventeen well-trained cyclists (31 ± 9 yr; V̇o_2max: 67 ± 6 mL × kg^-1 × min^-1) were randomized to groups performing five HIIT sessions (6 × 5 min intervals with 2.5 min of recovery) with (BFR) or without (HIIT) thigh cuffs occluding the legs. V̇o_2max, power output at 4 mmoL/L blood lactate (LT4), mean power output during 5-min maximal cycling (MPO_{5 min}), percentage of V̇o_2max used at LT4 (%V̇o_2max@LT4), hemoglobin mass, and blood volume (BV) were assessed. Muscle biopsies from m. vastus lateralis evaluated muscle cross-sectional area (CSA), capillaries, citrate synthase, hydroxyacyl-coenzyme A dehydrogenase, and cytochrome c oxidase subunit 4. The BFR group trained at a 42% lower power output than the HIIT group (177 ± 3 W vs. 307 ± 8 W, respectively, P < 0.01), but with no differences in heart rate or rate of perceived exertion. Both groups improved MPO_{5 min} by ⁓4%, with no changes in LT4, V̇o_2max, hemoglobin mass, and BV. HIIT showed a significant reduction in CSA for type 2 muscle fibers compared with BFR, whereas no changes were found in the other muscle analyses. BFR applied during a 6-day interval microcycle provides similar performance gains as traditional HIIT in well-trained cyclists.NEW & NOTEWORTHY Blood flow restriction training (BFR) enables well-trained cyclists to perform high-intensity interval training (HIIT) at lower power outputs while still achieving comparable improvements in performance and muscle adaptations after a 6-day interval microcycle training. By matching effort rather than power output, this approach could help manage training load without compromising physiological gains. These findings suggest that BFR could be a tool in the training program of competitive athletes, especially during periods requiring reduced mechanical stress.

Pericoronary adipose tissue (PCAT) attenuation from coronary computed tomography angiography (CCTA) is an imaging biomarker of coronary inflammation. Experimental evidence suggests that sympathetic activation and norepinephrine (NE) can alter perivascular adipose tissue (PVAT) composition. Whether NE stress reactivity relates to PVAT phenotype, as reflected by PCAT attenuation, or varies by chronic stress exposure is unclear. We studied 60 male physicians (30 with clinical burnout, 30 controls) without known cardiovascular disease. Participants underwent CCTA for PCAT assessment and Trier Social Stress Test to induce psychosocial stress. Plasma NE was measured at baseline, immediately, +15, +45, and +90 min poststress. Relative NE increase (immediately post stress minus baseline) was the primary NE index; absolute NE increase, NE area under the curve with respect to increase (AUC-I) and ground (AUC-G; total output) were secondary indices. Multivariable regression adjusted for burnout, age, waist circumference, low-density lipoprotein cholesterol, and segment stenosis score. Greater relative NE stress increase was independently associated with lower total PCAT attenuation (average across three coronary arteries; partial r² = 0.12, P = 0.010). Each 10% relative NE increase corresponded to ∼1 HU lower attenuation. Similarly, an absolute NE increase of 50 pg/mL (partial r² = 0.08, P = 0.036) and a 5,000-unit increase in NE AUC-I (partial r² = 0.07, P = 0.049) corresponded to ∼1 HU lower attenuation, whereas NE AUC-G showed no association (P = 0.35). Acute sympathetic stress reactivity, reflected by NE increase, is associated with a lipid-rich PVAT phenotype, as indicated by lower PCAT attenuation, supporting PVAT responsiveness to adrenergic stimulation. Excess NE reactivity may represent a biomarker of early coronary vulnerability.NEW & NOTEWORTHY This study highlights the association between acute norepinephrine (NE) stress reactivity and pericoronary adipose tissue (PCAT) attenuation, a marker of coronary inflammation. In male physicians, greater NE increase after acute psychosocial stress was linked to lower PCAT attenuation, reflecting a more lipid-rich perivascular adipose tissue phenotype. This suggests that heightened NE reactivity may indicate early coronary vulnerability. Burnout did not modify this relationship, pointing to NE reactivity as a distinct physiological pathway in cardiovascular risk.

We tested the hypothesis that excess cardiac activation (ECA) generates increased cardiovascular circuit flow at the onset of exercise. Thirty participants (14 females) performed 30 s of right-legged knee extension/flexion exercise at 50% of one-legged WR_PEAK to assess the normal cardiovascular adjustment at the onset of single-leg exercise (control; CON). ECA in isolation was accomplished in separate trials by initiating exercise with both the right leg and the occluded left leg (each at 50% one-legged WR_PEAK) to generate additional muscle mass activation of autonomic cardiac control without allowing the exercising left leg circulation to add to the cardiovascular circuit. Central (finger photoplethysmography) and peripheral (Doppler ultrasound) hemodynamics were measured continuously. ECA increased cardiac activation versus CON (Δ heart rate; 35.3 ± 8.4 vs. 24.5 ± 8.7 beats/min, P < 0.0001), which elevated ΔQ̇ (4.62 ± 1.62 vs. 3.48 ± 1.51 L/min, P < 0.001) as Δ stroke volume was not different between conditions. ECA increased Δ mean arterial pressure (11.9 ± 5.8 vs. 5.5 ± 5.6 mmHg, P < 0.0001) via ΔQ̇, as Δ total vascular conductance was also greater during ECA (36.6 ± 18.3 vs. 31.3 ± 15.1 mL/min/mmHg, P = 0.0120). Δ exercising leg blood flow (LBF; 2,594.3 ± 639.6 vs. 2,425.1 ± 550.9 mL/min, P = 0.0179), but not Δ leg vascular conductance, was greater in ECA vs. CON. These findings demonstrate that excess exercise-induced cardiac activation can create a greater increase in Q̇ and exercising leg perfusion at exercise onset without a change in exercising leg vasodilation magnitude during sub-maximal knee flexion/extension exercise.NEW & NOTEWORTHY Whether increasing cardiac activation above normal can increase cardiovascular circuit blood flow above normal at exercise onset in humans remained unclear. We found that excess exercise-induced cardiac activation created a greater increase in cardiac output via greater heart rate increases. Furthermore, exercising leg perfusion also increased to a greater extent due to elevated arterial blood pressure created by greater cardiac output. In conclusion, increased cardiac activation can improve cardiovascular circuit flow responses at exercise onset.