Previously, we observed divergent vascular responses to the cold pressor test (CPT) among young healthy female participants. This short report examined circulating hormones as contributors to this variability in a larger...Previously, we observed divergent vascular responses to the cold pressor test (CPT) among young healthy female participants. This short report examined circulating hormones as contributors to this variability in a larger cohort of female participants. We tested the hypothesis that gonadal hormones would be associated with vascular and muscle sympathetic nerve activity (MSNA) responses to the CPT. CPT responses from 20 young females tested in the early follicular phase of the menstrual cycle or placebo phase of oral contraceptive use were pooled for analyses. Venous blood samples were analyzed (radioimmunoassay; n=18) for circulating total testosterone, 17β-estradiol, progesterone, sex hormone binding globulin (SHBG), and free androgen index (FAI; [total testosterone]/[SHBG]). Mean arterial pressure (MAP; finger photoplethysmography), femoral blood flow (FBF; vascular ultrasound), femoral vascular conductance (FVC; FBF/MAP), and MSNA burst incidence (bursts/100hb; peroneal microneurography), were assessed at baseline and during a hand CPT (3-min). The CPT induced increases in MSNA (baseline: 10±5 CPT: 28±12bursts/100hb; P<0.01) and MAP (86±9 96±7mmHg; P<0.01), whereas changes in FVC were not significant (2.6±0.9 3.4±0.6mL/min/mmHg; P=0.89). Neither [17-β-estradiol] (R=0.07; P=0.27) nor [progesterone] (R<0.01, P=0.73) were associated with CPT-induced increases in MSNA, whereas FAI was positively associated with increases in MSNA (R=0.47; P<0.01). Likewise, neither [17β-estradiol] (R=0.11, P=0.65) nor [progesterone] (R=0.01, P=0.98) were associated with percent change in FVC (%FVC). However, there was a negative association between FAI and %FVC (R=0.49, P<0.01). These data suggest that bioavailable testosterone may be associated with CPT-induced increases in MSNA and peripheral vasoconstriction in young healthy females.
Roberts BM, Hendricks J, Guerriere Aaron K
… +11 more, Walker LA, Sczuroski CE, Geddis AV, Staab JE, Staab JS, Taylor KM, McClung JP, Foulis SA, Hughes JM, Petrovick M, Gaffney-Stomberg E
Trainees in US Army Basic Combat Training (BCT) frequently experience vitamin D deficiency and bone stress injuries. It remains unclear how genetic variation influences these outcomes, either through direct effects on sk...Trainees in US Army Basic Combat Training (BCT) frequently experience vitamin D deficiency and bone stress injuries. It remains unclear how genetic variation influences these outcomes, either through direct effects on skeletal adaptations to training or by increasing susceptibility to vitamin D insufficiency, which in turn affects skeletal adaptations and injury risk. This study investigated whether single nucleotide polymorphisms (SNPs) or genetic risk scores (GRS) previously related to vitamin D and bone health were associated with tibial bone microarchitecture during BCT. A cohort of 2,550 healthy young adults (36% female) underwent high-resolution peripheral quantitative computed tomography scans at the distal tibia before BCT and, in a subset (n = 1,514), again after 10 weeks of BCT. The following GRS or SNPs were evaluated: VDR, DBP, 25-OHD-GRS, Adults-GRS, Fracture-GRS, Pediatric-GRS, WNT-GRS, RANK-RANKL-OPG-GRS (RANK-GRS), and mesenchymal stem cell differentiation GRS (Mes-GRS). Multivariable linear regression models were adjusted for age, sex, BMI, and 25-OHD concentration. Following correction for multiple testing, 47 significant associations emerged. The Adult-GRS was negatively associated with volumetric bone mineral density (vBMD), trabecular vBMD, and bone volume fraction in White non-Hispanic, Hispanic trainees, and Other Races Combined. The Fracture-GRS was associated with trabecular and cortical microarchitecture across three group/ethnicities, while the Pediatric-GRS primarily showed associations in White non-Hispanic individuals. RANK-GRS correlated with trabecular microstructure in White non-Hispanic and Other Races Combined, and WNT-GRS was associated with cortical volumetric BMD in White non-Hispanics. No associations were observed between vitamin D SNPs or GRS and changes in bone during BCT. These findings suggest that GRS previously related to bone density and remodeling pathways are associated with bone microarchitecture in young adults, while vitamin D-related GRS were not associated with tibial microarchitecture during BCT.
Although general anaesthesia is a very common medical procedure, knowledge of how the brain physiologically recovers remains limited. In this randomized cross-over trial, we investigated brain physiology during recovery...Although general anaesthesia is a very common medical procedure, knowledge of how the brain physiologically recovers remains limited. In this randomized cross-over trial, we investigated brain physiology during recovery from general anaesthesia with sevoflurane or propofol. Using magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS), we quantified cerebral blood flow (CBF), the cerebral metabolic rate of oxygen (CMRO), and concentrations of cerebral lactate and N-acetyl aspartate before and after anaesthesia. Twenty-one healthy volunteers (male:female 10:11, mean age 23(18-32) years) underwent two sessions of general anaesthesia with either sevoflurane or propofol, spaced at least four weeks apart. MRI scans were performed before anaesthesia and again four hours, one day, and eight days after anaesthesia. CBF increased by 5.7% four hours after sevoflurane general anaesthesia (p=0.040), possibly reflecting reduced haemoglobin concentration. CMRO and N-acetyl aspartate concentrations did not change. In contrast, brain lactate was elevated four hours after both sevoflurane (14.7%, p=0.0006) and propofol (9.5%, p=0.01), and remained elevated one day after sevoflurane anaesthesia (13.2%, p=0.0008). This lactate increase occurred despite normal CMRO and may indicate enhanced glycolytic activity during post-anaesthetic recovery.
Studies involving breath-hold dives as deep as 60m have identified a spike in arterial PO (PaO) and PCO (PaCO) apparently associated with lung compression by water pressure as depth increases. Competitive breath-hold div...Studies involving breath-hold dives as deep as 60m have identified a spike in arterial PO (PaO) and PCO (PaCO) apparently associated with lung compression by water pressure as depth increases. Competitive breath-hold dives may exceed 100m, raising the possibility that a spike in PaCO might contribute to narcosis-like symptoms sometimes experienced. To predict the magnitude of this spike, three elite breath-hold divers were instrumented with radial artery catheters and had arterial blood specimens taken at the bottom on separate dives to 20, 40, 60, and 80m with another specimen either after beginning apnea but before leaving surface (one participant) or on arrival back at the surface while still apneic (two participants). Contrary to prior expectations, the greatest spike in PaO was at 40m (mean 29.3 kPa, 220 mmHg) and the trajectory of rise in PaCO also plateaued at 40m (mean 5.61 kPa, 42.1 mmHg [from a mean baseline of 2.53 kPa after pre-dive hyperventilation] and 5.54 kPa, 41.6 mmHg at 60m) before rising again after 60m (80m mean 6.9 kPa, 51.5 mmHg). This suggests that a spike in arterial gases associated with lung compression was detectable until the greatest proportional changes in lung volume with increasing pressure had occurred. Thereafter, PaO decreased through metabolism and PaCO increased through simple metabolic accumulation. That the compression effect seemed maximal at 40m (five atmospheres absolute pressure) may relate to the simple Boyle's Law predication that the lung may be compressed to close to residual volume (20-30% of total lung capacity) at this pressure.
Preeclampsia (PE) is a hypertensive disorder of pregnancy characterized by hypertension and organ dysfunction, and is associated with impaired placental perfusion and systemic endothelial dysfunction. Aerobic exercise ha...Preeclampsia (PE) is a hypertensive disorder of pregnancy characterized by hypertension and organ dysfunction, and is associated with impaired placental perfusion and systemic endothelial dysfunction. Aerobic exercise has been proposed as a potential non-pharmacological strategy to improve vascular function during pregnancy; however, its effects on fetoplacental microcirculation in PE remain poorly understood. Therefore, the objective of this study was to investigate whether maternal aerobic exercise during gestation could influence fetoplacental perfusion and maternal pathological features in an experimental model of PE induced by nitric oxide synthase inhibition. Fetoplacental and fetal regional perfusion were quantified using laser speckle contrast imaging across placental, umbilical, and multiple fetal vascular beds. In parallel, maternal cardiovascular parameters, including systolic blood pressure and heart weight, and renal parameters, including kidney weight and urinary protein excretion, were assessed, along with fetal and placental biometric measurements and placental angiogenic factors. PE was associated with impaired fetoplacental perfusion and maternal cardiovascular alterations, whereas maternal aerobic exercise was associated with improved fetoplacental microvascular perfusion and attenuation of maternal pathological features. These findings support maternal exercise as a potential non-pharmacological strategy to modulate fetoplacental vascular dysfunction in hypertensive pregnancy.
Sarcopenia is the age-related atrophy and weakening (decrease in force per cross-sectional area) of muscle fibers. In rat diaphragm muscle (DIAm), sarcopenia primarily affects type IIx/IIb fibers that generate greater sp...Sarcopenia is the age-related atrophy and weakening (decrease in force per cross-sectional area) of muscle fibers. In rat diaphragm muscle (DIAm), sarcopenia primarily affects type IIx/IIb fibers that generate greater specific force, have the fastest maximum shortening velocities (V), but display greater fatigue with repeated activation. We hypothesized that because of the selective effect of sarcopenia on type IIx/IIb DIAm fibers, V and peak power output of the DIAm decreases in old age, while endurance during repetitive isovelocity shortening is unaffected. Mid-costal DIAm strips were excised from 6-month (n=8; 4 female and 4 male) and 24-month (n=8; 4 female and 4 male) Fischer 344 rats. The DIAm was supramaximally stimulated using platinum plate electrodes to measure mechanical and endurance properties at 26oC. In 24- compared to 6-month old rats, maximum specific force of the DIAm decreased by ~35%, V slowed by ~20%, and peak power output was reduced by ~35%. During repetitive isovelocity (~30% V; approximating peak power output) contractions, endurance (the period during which power output was sustained) of the DIAm was not different between 6- and 24-month rats. The changes in DIAm mechanical properties corresponded to an age-related decline in the cross-sectional area of type IIx/IIb muscle fibers (~35%). We conclude that age-related atrophy of type IIx/IIb DIAm fibers underlies the changes in mechanical properties of the DIAm, which would only impact more forceful expulsive airway clearance and voiding behaviors of the DIAm. The resilience of type I and IIa DIAm fibers with aging ensures that force generation and endurance required for breathing is sustained in old age.
Transcutaneous spinal stimulation aims to target dorsal spinal roots, which deliver sensory information to the spinal cord. However, the stimulation waveform that most effectively recruits sensory fibres at the lowest in...Transcutaneous spinal stimulation aims to target dorsal spinal roots, which deliver sensory information to the spinal cord. However, the stimulation waveform that most effectively recruits sensory fibres at the lowest intensity has not been identified. The purpose of this study was to compare conventional and high-frequency burst-modulated stimulation waveforms in their ability to recruit sensory fibres, as assessed by H-reflex threshold, recruitment characteristics, and motor fibre activation. In participants with intact neurological function (n=12), soleus H-reflex recruitment curves were recorded for ten stimulation waveforms: a conventional waveform (400 μs), serving as the reference condition, high-frequency burst-modulated waveforms (2, 5, and 10 kHz) with the same total phase duration, and a longer conventional waveform (1000 μs), each delivered as biphasic and monophasic pulses. H-reflex threshold was higher for high-frequency waveforms: 2 kHz (biphasic: +63%; monophasic: +35%); 5 kHz (biphasic: +179%, monophasic: +109%); 10 kHz (biphasic: +307%, monophasic: +249%); and lower for the conventional 1000 μs waveform (biphasic: -39%, monophasic: -44%). Similarly, recruitment curve peak slope (mV/mA) was less steep for high-frequency waveforms: 2 kHz (biphasic: -43%, monophasic: -40%); 5 kHz (biphasic: -77%, monophasic: -40%); 10 kHz (biphasic: -82%, monophasic: -48%); and was steeper (+38%) for the monophasic conventional 1000 μs waveform. At stimulus intensity near H-reflex threshold, M-wave amplitude was larger for high-frequency waveforms. Overall, high-frequency waveforms were less effective than conventional waveforms of equal total phase duration at eliciting H-reflexes and showed more motor activation at near-threshold intensities.
The U.S. Army Ranger Training Course (RTC) is a multi-stressor environment including cognitive and physical stress coupled with repeated sleep and energy deficits over 61+ days. Previous investigations of physiological r...The U.S. Army Ranger Training Course (RTC) is a multi-stressor environment including cognitive and physical stress coupled with repeated sleep and energy deficits over 61+ days. Previous investigations of physiological responses to RTC operational stressors were conducted exclusively in males, leaving female responses uncharacterized. Therefore, this study aimed to identify changes in metabolic, growth, and sex hormones, inflammatory and iron markers in males and females undergoing RTC. Blood samples and body composition assessments (DXA) were collected at the start of RTC (Baseline (BL)) and at the end of each phase (Phase (P)1 - general field, P2 - mountains, P3 - swamp). During each phase, daily urine sampling and measures of energy balance (doubly labeled water method) occurred. Females experienced physiological changes primarily in P2, with reductions in estradiol (mean difference [95% Confidence Interval]: -79.29 [-115.32, -43.26]), progesterone (-1.48 [-2.70, -0.26]), testosterone (-0.74 [-1.43, -0.04]), free testosterone: -12.70 [-23.23, -2.17]), thyroid stimulating hormone (TSH; -0.54 [-1.03, -0.05]), and insulin-like growth factor 1 (IGF-1; -92.58 [-121.28, -63.88]) compared to BL. Males demonstrated significant decreases in free testosterone, TSH, triiodothyronine (T), IGF-1, hemoglobin, and hematocrit across all three phases compared to BL (all, p < 0.05), with the largest changes in P3 for TSH (-0.66, [-1.21, -0.11]), T (-0.30 [-0.41, -0.20]), IGF-1 (-104.70 [-116.52, -92.88]), hemoglobin (-1.32 [-1.71, -0.94]), and hematocrit (-3.89 [-5.02, -2.75]). Ferritin increased across all phases compared to BL regardless of sex ( < 0.05). These findings indicate that multi-stressor environments may disproportionately affect male physiological markers, whereas females exhibited fewer, phase-specific changes.
Chronic obstructive pulmonary disease (COPD) is a respiratory disease with systemic complications including vascular dysfunction. Aerobic exercise improves blood pressure, endothelial function, and muscle angiogenesis in...Chronic obstructive pulmonary disease (COPD) is a respiratory disease with systemic complications including vascular dysfunction. Aerobic exercise improves blood pressure, endothelial function, and muscle angiogenesis in health and disease, but these effects in COPD are inconsistent. The elastase and LPS-induced emphysema (ELA-LPS) model with exacerbation replicates COPD cardiovascular comorbidities. We aimed to assess the impact of aerobic exercise on blood pressure and endothelial determinants in this model. Male Wistar rats were assigned to four groups: controls (Ctrl), controls with exercise (Ctrl+Ex), emphysema (ELA-LPS), and emphysema with exercise (ELA-LPS+Ex). After 4 weeks of treadmill training, we assessed respiratory parameters, V̇O₂max, heart rate, systolic/diastolic/mean arterial pressures, skeletal muscle capillarization, and ex vivo vascular reactivity. At baseline, compared to Ctrl, ELA-LPS animals exhibited reduced V̇O₂max, elevated blood pressure, and enhanced endothelium-dependent vasorelaxation via COX-dependent pathways. Aerobic exercise increased exercise capacity, lowered heart rate (HR), and reduced blood pressure (BP) in both groups. In Ctrl+Ex, aerobic exercise enhanced endothelium-dependent relaxation through NO signalling and increased muscle capillarization. In contrast, in ELA-LPS+Ex, aerobic exercise did not further increased vasorelaxation, although NO-dependence of the endothelium-dependent relaxation was restored, and no increase in muscle capillarization was observed. Aerobic exercise training improved HR and BP in emphysema but failed to fully restore microvascular adaptations, suggesting disease-specific vascular remodelling. These findings highlight a complex interplay between training-induced and disease-induced vascular changes. Clinical studies are warranted to define vascular phenotypes of patients with COPD responsive to aerobic exercise-induced blood pressure reduction.
During spaceflight, the lack of gravity-induced hydrostatic pressure gradients in the body results in a headward fluid shift hypothesized to play a role in pathophysiological changes in the cardiovascular, ocular, and ce...During spaceflight, the lack of gravity-induced hydrostatic pressure gradients in the body results in a headward fluid shift hypothesized to play a role in pathophysiological changes in the cardiovascular, ocular, and central nervous systems. Here, 24 subjects (n=8 control) underwent 60 days of strict 6° head-down tilt (HDT) bedrest, an analog of spaceflight where we tested the ability of daily 30 min artificial gravity (AG) exposure via short-arm human centrifugation (intermittent AG, n=8, and continuous AG, n=8) to reverse the HDT-induced headward fluid shift. Right internal jugular vein (IJV) cross-sectional area (2D ultrasound), and near-infrared spectroscopy measures of total hemoglobin concentration ([HbT]) in the prefrontal cortex and gastrocnemius muscle were measured before, during, and after centrifugation. IJV area decreased from 0.88 cm2 (95% CI: 0.62 - 1.13) pre-AG to 0.33 cm2 (0.24 - 0.42, P<0.001) in the first 2 min of continuous AG and remained partially collapsed while exposed to AG, with similar results seen during application of intermittent AG; [HbT] in the gastrocnemius muscle increased by 78.7µM (13 - 177 µM, p<0.0001) during AG, with smaller decreases of [HbT] in the head (p<0.001). Overall, AG resulted in a rapid shift of blood volume from the upper to the lower body; however, beneficial fluid shifting towards the lower limbs during AG appear to only be present during active countermeasure application, regardless of intermittent or continuous AG application. Thus, AG may be an effective countermeasure to physiological changes resulting from the spaceflight-induced headward fluid shift, dependent on duration and dose of AG.
In vitro fertilization (IVF) is an effective treatment for infertility; however, IVF may increase future maternal cardiovascular disease (CVD) risk. Vascular dysfunction, characterized by increased large elastic artery s...In vitro fertilization (IVF) is an effective treatment for infertility; however, IVF may increase future maternal cardiovascular disease (CVD) risk. Vascular dysfunction, characterized by increased large elastic artery stiffness and endothelial dysfunction, predicts future CVD risk. However, whether IVF use influences maternal vascular dysfunction is unknown. We studied premenopausal women with a live birth within the past 1-5 yr conceived either without medical assistance ( = 24) or via IVF ( = 15), matched for age, body fat percentage, and seated blood pressure. Large artery stiffness (carotid β-stiffness index) and endothelial function (brachial artery flow-mediated dilation) were assessed after 10 min of supine rest following an overnight fast. Large artery stiffness was greater in the IVF group compared with the reference group (6.5 ± 1.9 vs. 5.08 ± 1.2 U, = 0.022); endothelial function did not differ ( = 0.619). To explore potential mechanisms, mouse aortas were incubated with serum from a subset of participants ( = 11/group) to assess the influence of circulating factors on arterial stiffness (via elastic modulus). The elastic modulus was 28% higher in the group treated with serum from IVF patients relative to the reference group ( = 0.078), suggesting that circulating factors may contribute to observed differences in large artery stiffness. Follicle-stimulating hormone (FSH) concentrations were greater in the IVF group compared with the reference group ( = 0.026), and FSH concentrations were positively associated with in vivo large artery stiffness ( = 0.57, < 0.001). Large artery stiffness is elevated in individuals with a history of IVF-conceived live birth, potentially related to circulating factors, including FSH. Infertility is associated with increased risk of cardiovascular disease in women related to vascular dysfunction (i.e., increased large artery stiffness, impaired endothelial function). In vitro fertilization (IVF) is commonly used to treat infertility, but the effects of IVF on maternal vascular function remain unclear. This study demonstrates, for the first time, that large artery stiffness is elevated in women who conceived via IVF within the past 1-5 yr, potentially due in part to circulating factors.
Walking energy consumption is higher in people with versus without a transtibial amputation, but the underlying reasons are poorly understood. Active prostheses that restore ankle power do not necessarily decrease walkin...Walking energy consumption is higher in people with versus without a transtibial amputation, but the underlying reasons are poorly understood. Active prostheses that restore ankle power do not necessarily decrease walking energy consumption, suggesting other reasons than a lack of ankle power for the increased energy consumption. Transtibial amputation impacts walking stability, as evidenced by the increased fall risk, and there is an energetic cost associated with stabilizing walking. It is, however, unclear how transtibial amputation affects the energetic cost of stabilizing walking. We assessed the metabolic cost of stabilizing walking against treadmill belt speed perturbations (SD = 0.13 m/s) in 16 subjects with and 23 subjects without a transtibial amputation at three walking speeds between 0.6 and 1.6 m/s. We focused on sagittal plane stability, as a transtibial amputation disables muscle-driven modulation of the ankle torque, which plays an important role in controlling walking in the sagittal plane at slow speeds. Perturbations induced 0.24 W/kg larger increases in energy consumption across walking speeds in subjects with than without a transtibial amputation. Whereas mean reductions in step length in response to perturbations were similar between groups, individuals with an amputation increased step length variability of their intact leg more than individuals without an amputation, especially at low speeds. As continuous control is required for unperturbed walking, an increased metabolic cost of stabilizing walking might explain-at least partially-the higher energetic cost of walking. These insights are important when seeking to reduce the metabolic cost of walking after transtibial amputation. The higher metabolic cost of walking in individuals with versus without a transtibial amputation is poorly understood, hindering the design of interventions. We demonstrated that transtibial amputation considerably increases the energy consumption for stabilizing walking in the sagittal plane and increases the reliance on step length adjustments to stabilize walking. This opens perspectives for restoring walking energetics after amputation through prostheses that support sagittal plane stability.
Although estrogen is known to confer cardioprotective benefits in cisgender women, transgender women on gender-affirming hormone therapy may experience unique cardiovascular risks. Emerging evidence suggests that feminiz...Although estrogen is known to confer cardioprotective benefits in cisgender women, transgender women on gender-affirming hormone therapy may experience unique cardiovascular risks. Emerging evidence suggests that feminizing hormone therapy may confer both beneficial and adverse effects on the cardiovascular, renal, and hepatic systems. In this cross-sectional study, transgender women receiving gender-affirming hormone therapy with orchiectomy ( = 15) or without orchiectomy ( = 15) were compared with age-matched cisgender men ( = 15) and cisgender women ( = 15). Transgender women had received hormone therapy for 11 ± 3 yr. Serum estradiol concentrations were significantly lower in cisgender men (33 ± 10 pg·mL) than in transgender women with orchiectomy (141 ± 47 pg·mL), transgender women without orchiectomy (116 ± 41 pg·mL), and cisgender women (131 ± 38 pg·mL), whereas serum testosterone concentrations were significantly higher in cisgender men (22.0 ± 6.1 nM) compared with the other groups (1.2 ± 1.1, 0.6 ± 0.3, and 1.0 ± 0.3 nM) (all < 0.001). No statistically significant group differences were observed in brachial-ankle pulse wave velocity, brachial artery flow-mediated dilation, postocclusive skin reactive hyperemia, or blood nitric oxide concentrations (all > 0.05). Blood urea nitrogen, creatinine, and liver enzyme concentrations were significantly higher in cisgender men than in the other groups (all < 0.05). Collectively, these results indicate that no statistically significant differences were observed in macro- and microvascular function, as well as liver and renal function, between transgender women (with or without orchiectomy) and cisgender women. The primary finding of the present study is that transgender women demonstrate similar macrovascular and microvascular function as well as renal and hepatic function to cisgender women. Regardless of marked differences in circulating sex hormone profiles, no evidence of vascular dysfunction or organ impairment was observed in transgender women. These findings suggest that prolonged exposure to an estrogen-dominant hormonal milieu is sufficient to induce a female-typical physiological phenotype across multiple organ systems.
Between-individual variability in physiological adaptations to endurance exercise training is often interpreted as reflecting stable differences in training responsiveness. However, whether the capacity for physiological...Between-individual variability in physiological adaptations to endurance exercise training is often interpreted as reflecting stable differences in training responsiveness. However, whether the capacity for physiological adaptation itself represents a stable, individual-specific trait under repeated exposure to the same training stimulus remains unclear. This study investigated the reproducibility of within-individual adaptations to repeated endurance training. Forty-two middle-aged, untrained men and women completed two similar 8-wk endurance training periods (TP and TP), separated by an 8-wk detraining period. Assessments spanned multiple physiological and performance outcomes, including hemoglobin mass (Hb), skeletal muscle citrate synthase (CS) activity, capillaries·fibre, maximal oxygen uptake (V̇o), and 15-min maximal mean power output (MMPO). Within-individual reproducibility was evaluated using intraclass correlation coefficients with [95% confidence intervals]. Participants completed 23.9 (0.4) and 23.8 (0.7) training sessions in TP and TP, respectively, with minimal within-individual variation. Baseline values were highly consistent between periods for V̇o (0.98 [0.97, 0.99]), MMPO (0.96 [0.93, 0.97]), and most other outcomes, indicating effective detraining. Nevertheless, reproducibility of within-individual adaptations was for Hb (0.00 [0.00, 0.30]), CS activity (0.15 [0.00, 0.33]), capillaries·fibre (0.00 [0.00, 0.36]), V̇o (0.19 [0.00, 0.37]), and MMPO (0.20 [0.00, 0.37]). Within-individual variability in hematological and skeletal muscle adaptations accounted for little of the within-individual variability in V̇o and MMPO responses. This study demonstrates that individual adaptations to endurance training exhibit limited reproducibility across multiple physiological and performance outcomes. These findings indicate that physiological adaptability to endurance training does not reflect a stable, individual-specific attribute but instead emerges from dynamic and context-dependent biological processes. Repeating the same exercise training intervention within the same individuals after an adequate detraining period provides a direct test of whether physiological adaptations are reproducible within individuals. This study demonstrates that individual physiological adaptations to a repeated endurance training program are largely nonreproducible across multiple physiological and performance outcomes, despite highly standardized and closely supervised training conditions. The substantial within-individual response variability challenges the notion that physiological training responsiveness is a stable, trait-like characteristic.
The experimental aim of this study was to determine, in vitro, the effect of estrogen on brain endothelial cell oxidative stress, apoptotic susceptibility, and tissue-type plasminogen activator (t-PA) release. Human cere...The experimental aim of this study was to determine, in vitro, the effect of estrogen on brain endothelial cell oxidative stress, apoptotic susceptibility, and tissue-type plasminogen activator (t-PA) release. Human cerebral microvascular endothelial cells (hCMECs) were cultured and treated with 17β-estradiol (100 nM), the primary and most biologically active endogenous form of estrogen in humans, for 24 h. Intracellular reactive oxygen species production was significantly lower (∼15%; > 0.01) in hCMECs treated with 17β-estradiol; however, antioxidant proteins superoxide dismutase-1 (28.6 ± 11.0 vs. 36.2 ± 11.9 AU) and catalase (33.6 ± 14.0 vs. 32.1 ± 14.7 AU) were not significantly altered by 17β-estradiol. Although, there were no significant differences in the basal intracellular expression of either total caspase-3 (159.8 ± 84.9 vs. 143.6 ± 39.2 AU) or active caspase-3 (13.5 ± 4.5 vs. 15.4 ± 6.7 AU) between untreated and 17β-estradiol-treated hCMECs; the increase in active caspase-3 in response to the apoptosis stimulus staurosporine was significantly lower (∼30%; = 0.02) in 17β-estradiol-treated (from 15.5 ± 6.7 to 184.5 ± 43.8 AU) compared with untreated (from 13.5 ± 4.5 to 257.6 ± 34.4 pg/mL) hCMECs. t-PA release in response to thrombin was significantly higher ( = 0.02) in 17β-estradiol-treated (from 41.6 ± 10.8 to 61.1 ± 9.2 pg/mL; ∼45% increase) compared with untreated (43.4 ± 9.2 to 48.0 ± 11.5 pg/mL; ∼10% increase) hCMECs. In summary, 17β-estradiol decreases oxidative stress, enhances apoptotic resistance, and increases fibrinolytic capacity in human brain microvascular endothelial cells in vitro. Reduced risk of cerebrovascular disease and thrombotic events attributed to estrogen may be mediated, in part, by these beneficial endothelial effects. The cerebrovascular protective effects of estrogen are diverse, complex, and not fully understood. This study provides novel data demonstrating that 17β-estradiol decreases oxidative stress, enhances apoptotic resistance, and increases fibrinolytic capacity in human brain microvascular endothelial cells in vitro. These changes in endothelial cell phenotype have been linked (clinically and epidemiologically) to less cerebrovascular dysfunction and reduced ischemic stroke risk.