Journal of applied physiology最新文献

Obstructive sleep apnea (OSA) is a chronic sleep-related breathing disorder that is highly prevalent in individuals with posttraumatic stress disorder (PTSD). The reason for this high prevalence remains unclear. We hypothesized that breathing instability, one of the key contributors to OSA, may be altered in PTSD and predispose OSA. Healthy participants (214 females, 98 males) aged 17 to 42 (M = 19.92; SD = 2.85) completed online questionnaires measuring PTSD symptomatology, sleep disturbances, and self-reported breathlessness. A subset of these participants (16 females, 14 males) aged 18 to 42 (M = 23.50; SD = 7.18) completed an in-lab breathing instability assessment, whereby they performed a series of 20-second and maximal duration breath-holds. PTSD severity positively predicted subjective perceptions of breathlessness (P < 0.001) but not objective measures of breathing instability, namely ventilation following 20-s breath-holds (P = 0.93) and maximal breath-hold duration (P = 0.41). These results suggest that breathing instability may not be the driving factor behind the high prevalence of OSA in PTSD. Instead, other factors such as a low arousal threshold, elevated ventilatory responses to arousal, or coexisting insomnia may explain the high rates of OSA in PTSD. One explanation for the discrepancy between subjective breathlessness and breathing stability measures relating to PTSD severity may be that hypervigilance and increased anxiety impacted self-perceptions of breathlessness while not altering breathing instability per se.NEW & NOTEWORTHY Obstructive sleep apnea (OSA) is more common in individuals with posttraumatic stress disorder (PTSD) than the general population for unknown reasons. This study assessed one of the key contributors to OSA, respiratory control instability, in young students with a range of posttraumatic stress symptoms. Although individuals with high PTSD symptoms reported increased subjective breathlessness, objectively measured breathing instability was not altered, suggesting respiratory instability is unlikely to increase the risk of OSA in PTSD.

Human cutaneous microdialysis approaches for assessing nitric oxide (NO)-dependent blood flow include local heating (LH) of the skin until a plateau is reached, followed by infusion of a NO synthase inhibitor such as N^G-nitro-l-arginine methyl ester (l-NAME); however, varied methods of quantifying and expressing NO-dependent vasodilation can obfuscate data interpretation and reproducibility. We retrospectively assessed NO-dependent vasodilation during LH to 39°C or 42°C, calculated as the 1) absolute contribution of the NO-dependent component (along with baseline and the non-NO-dependent component) to the total cutaneous vascular conductance (CVC) response to LH, normalized to maximal CVC (%CVC_max); 2) difference in %CVC_max (Δ%CVC_max) between the LH plateau and post-NO synthase inhibition (l-NAME plateau; Δ%CVC_max = LH plateau - l-NAME plateau); 3) percentage of the LH plateau attributable to Δ%CVC_max (%plateau = Δ%CVC_max/LH plateau × 100); and 4) %plateau when correcting for baseline. The LH plateaus during 39°C and 42°C were 48 ± 17%CVC_max (9 ± 5% baseline; 2 ± 4% non-NO dependent; 36 ± 15% NO dependent) and 88 ± 10%CVC_max (15 ± 8% baseline; 9 ± 10% non-NO dependent; 64 ± 13% NO dependent), respectively. The absolute contributions of the non-NO-dependent and NO-dependent components of the response (P < 0.0001) and the Δ%CVC_max (66 ± 14 vs. 38 ± 15%) were greater during 42°C compared with 39°C (all P ≤ 0.02); however, there were no differences between the two protocols in %plateau (75 ± 13 vs. 80 ± 10%; P = 0.57) or %plateau_BL (88 ± 14 vs. 95 ± 8%; P = 0.31). For both protocols, the values were greater for %plateau_BL versus Δ%CVC_max and %plateau (P ≤ 0.0001), and for %plateau versus Δ%CVC_max (P ≤ 0.05). Quantification of NO-dependent skin vasodilation responses to LH is dependent upon the mathematical approach and verbal description, which can meaningfully impact data interpretation and reproducibility.NEW & NOTEWORTHY Local heating protocols are commonly used in conjunction with intradermal microdialysis for assessing nitric oxide (NO)-dependent microvascular function in humans, but various methods used to quantify and describe NO-dependent vasodilation may impact data interpretation. We compared four approaches for quantifying NO-dependent cutaneous vasodilation during local heating at 39°C and 42°C. We identify discrepancies in calculated NO-dependent dilation responses that are dependent upon the mathematical approach and meaningfully impact data interpretation and reproducibility.

The reliability of blood pressure (BP) measured during submaximal and maximal exercise, and confounding effects of biological sex, remain to be fully established but have implications for using exercise BP as a cardiovascular risk factor. We hypothesize that exercise BP test-retest reliability will not differ between sexes but will be higher during submaximal compared to maximal exercise. Eighty-four participants (22 ± 5 yr; 36 females) completed two maximal treadmill tests (modified Bruce protocol) separated by ≥2 days. Exercise BP was measured every 90 s using automated auscultation (Tango M2 monitor). Breath-by-breath oxygen uptake was analyzed. Test-retest reliability was assessed using two-way, mixed-effects, consistency, single-rater intraclass correlation coefficient (ICC) analysis on the total group and separated by sex at submaximal and maximal exercise. Systolic BP during submaximal (ICC = 0.65 [0.49-0.76], P < 0.01) and maximal (ICC = 0.66 [0.52-0.77], P < 0.01) exercise both displayed substantial reliability between visits. In contrast, the SBP/MET slope showed poor submaximal (ICC = 0.12 [-0.09-0.33], P = 0.13) but substantial maximal (ICC = 0.63 [0.48-0.75], P < 0.01) exercise reliability. Females showed substantial reliability in submaximal systolic BP (ICC = 0.73 [0.53-0.85], P < 0.01) and peak systolic BP (ICC = 0.74 [0.54-0.87], P < 0.01) and SBP/MET slope (ICC = 0.78 [0.60-0.88], P < 0.01); the submaximal SBP/MET slope had fair reliability (ICC = 0.28 [-0.06-0.56], P = 0.05). Males showed moderate reliability in submaximal systolic BP (ICC = 0.53 [0.26-0.72], P < 0.01) and peak systolic BP (ICC = 0.41 [0.15-0.62], P < 0.01) and SBP/MET slope (ICC = 0.48 [0.22-0.67], P < 0.01); the submaximal SBP/MET slope had poor reliability (ICC = 0.06 [-0.18-0.31], P = 0.32). Systolic BP showed similar reliability during submaximal and maximal exercise, with females demonstrating higher reliability in exercise systolic BP compared to males.NEW & NOTEWORTHY Limited work has assessed the reliability of exercise blood pressure (BP) in young healthy males and females. Our results demonstrate that systolic BP test-retest reliability did not differ between submaximal and maximal exercise. Sex-specific analysis found that females had higher reliability in exercise systolic BP than males. Despite the acceptable average reliability, exercise BP measured using automated auscultation possesses wide confidence intervals, which impact sample size requirements in future trials.

Quantitating exercise ventilatory and gas exchange dynamics affords insights into physiological control processes and cardiopulmonary dysfunction. We designed a novel waveform, the chirp waveform, to efficiently extract moderate-intensity exercise response dynamics. In the chirp waveform, work rate fluctuates sinusoidally with constant amplitude as sinusoidal period decreases progressively from ∼8.5 to 1.4 min over 30 min of cycle ergometry. We hypothesized that response dynamics of pulmonary ventilation (V̇e) and gas exchange [oxygen uptake (V̇o₂) and carbon dioxide output (V̇co₂)] extracted from chirp waveform are similar to those obtained from stepwise transitions. Thirty-one participants [14 young healthy, 7 older healthy, and 10 patients with chronic obstructive pulmonary disease (COPD)] exercised on three occasions. Participants first performed ramp-incremental exercise for gas exchange threshold (GET) determination. In randomized order, the next two visits involved either chirp or stepwise waveforms. Work rate amplitude (20 W to ∼95% GET work rate) and exercise duration (30 min) were the same for both waveforms. A first-order linear transfer function with a single system gain (G) and time constant (τ) characterized response dynamics. Agreement between model parameters extracted from chirp and stepwise waveforms was established using Bland-Altman analysis and Rothery's concordance coefficient (RCC). V̇e, V̇o₂, and V̇co₂ Gs showed no systematic bias (P > 0.178) and moderate-to-good agreement (RCC > 0.772, P < 0.01) between waveforms. Similarly, no systematic bias (P = 0.815) and good agreement (RCC = 0.837, P < 0.001) was found for τV̇o₂. Despite moderate agreement for τV̇co₂ (RCC = 0.794, P < 0.001) and τV̇e (RCC = 0.722, P = 0.083), chirp τ was less [-6.9(11.7) s and -12.2(22.5) s, respectively]. We conclude that the chirp waveform is a promising method for measuring exercise response dynamics and investigating physiological control mechanisms.NEW & NOTEWORTHY We investigated the ability of a novel waveform to extract exercise ventilatory and gas exchange dynamics. In the chirp waveform, work rate fluctuates sinusoidally with constant amplitude as sinusoidal period decreases progressively over 30 min of exercise. In a study of 31 healthy individuals and patients with COPD, comparison of exercise dynamics derived from chirp to those from stepwise waveforms suggests that the chirp waveform is a promising method for derivation of exercise response dynamics.

Plasma glycerol and free fatty acid concentrations decrease following oral glucose consumption, but changes in the rate of lipolysis during an oral glucose tolerance test (OGTT) have not been documented in conjunction with changes in fatty acid (FA) oxidation or reesterification rates in healthy individuals. After a 12-h overnight fast, 15 young (21-35 yr; 7 men and 8 women) and 14 older (60-80 yr; 7 men and 7 women) participants had the forearm vein catheterized for primed continuous infusion of [1,1,2,3,3-²H]glycerol. A contralateral hand vein was catheterized for arterialized blood sampling. Indirect calorimetry was performed simultaneously to determine total FA and carbohydrate (CHO) oxidation rates (Rox). Total FA reesterification rates (Rs) were estimated from tracer-measured lipolytic and FA oxidation rates. After a 90-min equilibration period, participants underwent a 120-min, 75-g OGTT. Glycerol rate of appearance (Ra), an index of lipolysis, decreased significantly from baseline 5 min postchallenge in young participants and 30 min in older participants. At 60 min, FA Rox decreased in both groups, but was significantly higher in older participants. Between 5 and 90 min, CHO Rox was significantly lower in older participants. In addition, FA Rs was significantly lower in older participants at 60 and 90 min. The area under the curve (AUC) for FA Rox was greater than that for FA Rs in older, but not in young participants. Our results indicate that, in aging, the postprandial suppression of lipolysis and FA oxidation are delayed such that FA oxidation is favored over CHO oxidation and FA reesterification.NEW & NOTEWORTHY To our knowledge, our investigation is the first to demonstrate changes in lipolysis during an oral glucose tolerance test (OGTT) in healthy young and older individuals. Plasma glycerol and free fatty acid concentrations changed after glycerol rate of appearance (Ra), indicating that plasma concentrations are incomplete surrogates of the lipolytic rate. Moreover, simultaneous determinations of substrate oxidation rates are interpreted to indicate that metabolic inflexibility in aging is characterized by delayed changes in postprandial substrate utilization related to the lipolytic rate.

Several experimental studies have found that females have higher particle deposition in the airways than males. This has implications for the delivery of aerosolized therapeutics and for understanding sex differences in respiratory system response to environmental exposures. This study evaluates several factors that potentially contribute to sex differences in particle deposition, using scale-specific structure-function models of one-dimensional (1-D) ventilation distribution, particle transport, and deposition. The impact of gravity, inhalation flow rate, and dead space are evaluated in 12 structure-based models (7 females; 5 males). Females were found to have significantly higher total, bronchial, and alveolar deposition than males across a particle size range from 0.01 to 10 μm. Results suggest that higher deposition fraction in females is due to higher alveolar deposition for smaller particle sizes and higher bronchial deposition for larger particles. Females had higher alveolar deposition in the lower lobes and slightly lower particle concentration in the left upper lobe. Males were found to be more sensitive to changes due to gravity, showing greater reduction in bronchial deposition fraction. Males were also more sensitive to change in inhalation flow rate and to scaling of dead space due to the larger male baseline airway size. Predictions of sex differences in particle deposition-that are consistent with the literature-suggest that sex-based characteristics of lung and airway size interacting with particle size gives rise to differences in regional deposition.NEW & NOTEWORTHY Sex differences in airway tract particle deposition are analyzed using computational models that account for scale-specific structure and function. We show that sex-related differences in lung and airway size can explain experimental observations of increased deposition fraction in females, with females tending toward enhanced fine particle deposition in the alveolar airways and enhanced bronchial deposition for larger particles.

Endurance performance declines with advancing age. Of the three main physiological factors that determine endurance running performance [maximal oxygen consumption (V̇o_2max), lactate threshold, and running economy (RE)], V̇o_2max appears to be most affected by age. Although endurance performance declines with age, recently, endurance performance has rapidly improved in master athletes as the number of master athletes competing in endurance events has increased. Master athletes represent an intriguing model to study healthy aging. In this case study, we reassessed the physiological profile of a 76-yr-old distance runner who broke the marathon world record for men over 70 yr of age in 2018. This runner was tested a few months before breaking the world record and retested in 2024. Between 2018 and 2024, his marathon running velocity decreased significantly. Therefore, the purpose of this case study was to determine the physiological changes that explain his performance decline. RE remained similar to 2018, and while there was not a clear breakpoint in blood lactate, he still likely runs marathons at a high percentage (∼90%) of his V̇o_2max. However, V̇o_2max declined by 15.1%. HRmax declined by 3.2% and maximal O₂ pulse declined by 12.4%, suggesting that maximal stroke volume and/or arteriovenous O₂ difference decreased. Altogether, although this marathoner continues to compete at an elite level, his performance has declined since his record-breaking marathon due to a reduction in V̇o_2max. This is likely caused by reductions in maximal stroke volume and/or arteriovenous O₂ difference. We speculate that these changes reflect primarily age-related processes.NEW & NOTEWORTHY We performed 6-yr follow-up testing on a world record-breaking master marathon runner. We determined that his performance declined since his record-breaking marathon in 2018 primarily due to a reduction in V̇o_2max. His max heart rate (HR) changed minimally, but his peak O₂ pulse decreased, suggesting that his maximal stroke volume and/or arteriovenous O₂ difference decreased. These changes likely reflect primarily age-related effects in the absence of an overt pathological disease process.

Chronic stress can directly and indirectly promote carcinogenesis through immune, metabolic, and microbial pathways. Our overarching hypothesis is that reducing chronic stress will have important implications for colorectal cancer (CRC) risk reduction among vulnerable and high-risk populations. A promising approach for reducing chronic stress is mindfulness. Mindfulness is a meditation-based technique that achieves a state of mind that is used to experience higher awareness or consciousness. Existing small studies suggest mindfulness can positively regulate stress response in a way that translates to anticancer effects, including reduced systemic inflammation. We propose to evaluate an 8-wk mindfulness intervention delivered in a hybrid format (synchronous and asynchronous sessions) among 40 Black women at elevated risk of CRC who reside in vulnerable communities and who report moderate to high perceived stress. At baseline and postintervention, participants will provide blood, hair, and stool; undergo body composition analysis; and complete mood and lifestyle-related surveys. The specific aims are to assess the feasibility and acceptability of the intervention and explore changes on stress, weight, fasting glucose, inflammation markers, and the gut microbiota-risk markers and risk pathways associated with CRC. The data generated through this project will inform if mindfulness is a feasible option for CRC risk reduction among high-risk individuals.NEW & NOTEWORTHY We propose to evaluate an 8-wk mindfulness intervention delivered in a hybrid format (synchronous and asynchronous sessions) among 40 Black women at elevated risk of CRC who reside in vulnerable communities and who report moderate to high perceived stress. The specific aims are to assess the feasibility and acceptability of the intervention and explore changes on stress, weight, fasting glucose, inflammation markers, and the gut microbiota-risk markers and risk pathways associated with CRC.

The aim of this study was to determine whether the capacity of remote ischemic preconditioning (IPC) against endothelial ischemia/reperfusion (I/R) injury changes across the menstrual cycle in premenopausal women and to compare IPC responses to postmenopausal women. Thirty-five women were studied (22 premenopausal/13 postmenopausal). Changes in endothelial function were determined during the early follicular vs. the late follicular phase (after positive urine ovulation test; Study 1), vs. the mid-luteal phase (after positive urine progesterone test; Study 2), and vs. estrogen-deficient postmenopausal women; Study 3). Endothelium-dependent vasodilation was assessed by the forearm blood flow (FBF) to reactive hyperemia with/without I/R injury with remote IPC (3 × 5 min cycles of upper arm ischemia). In the premenopausal women, peak FBF responses during the early follicular phase were blunted 20% (P < 0.0001) with I/R injury (from baseline: 23.4 ± 6.2 to 19.5 ± 4.9 mL/100 mL tissue/min) compared with the late follicular/mid-luteal phases despite IPC. In postmenopausal women, peak FBF was diminished (from: 21.1 ± 5.1 to 17.2 ± 4.4 mL/100 mL tissue/min), and total FBF (area under the curve) was decreased a third (-32%; P < 0.001) with I/R injury. Protection from I/R injury was preserved during the late follicular (from baseline: 21.7 ± 5.3 to 24.8 ± 5.9 mL/100 mL tissue/min; P = 0.109) and mid-luteal phases (from: 25.1 ± 3.9 to 27.2 ± 5.7 mL/100 mL tissue/min; P = 0.267). Reduced estrogen during the early follicular phase and the rise in estrogen associated with ovulation and the mid-luteal phase may contribute to changes in IPC-mediated protection in premenopausal women and shed light on how cardioprotection may change with ovarian hormone deficiency with the menopause transition.NEW & NOTEWORTHY The capacity of remote ischemic preconditioning to protect against vascular endothelial ischemia/reperfusion injury varies widely across the phases of the menstrual cycle in healthy premenopausal women. Robust protection was afforded during the late follicular and mid-luteal phases. In contrast, weakened protection was demonstrated during the early follicular phase, with a level of impairment similar to estrogen-deficient postmenopausal women.

Microphysiological systems (MPS) or "organ-on-a-chip" models are sophisticated tools that harness techniques from cell biology, tissue engineering, and microengineering to recapitulate human physiology. Typically, MPS are biofabricated three-dimensional (3-D) tissue constructs integrated into platforms designed to mimic the tissue microenvironment and provide functional outputs. Over the past decade, researchers have endeavored to manufacture high-throughput, high-fidelity MPS models of all major human organs. By incorporating patient-derived cells, researchers have produced biomimetic models of tissues with disease-linked genetic mutations capable of exhibiting patient heterogeneity. This work has demonstrated that MPS more closely model organotypic function and pathophysiology than traditional two-dimensional (2-D) culture systems. Moreover, investigators have shown that human MPS are better predictors of drug efficacy and toxicity than animal models. Thus, MPS have emerged as a promising candidate to improve the efficacy and safety of preclinical trials. In this mini-review, we provide an overview of current advances in MPS models, their applications in mechanistic research, and relevance to drug screening. Finally, we discuss current investments in MPS development by the United States federal government and research institutions around the world to advance translational medicine.