Journal of applied physiology最新文献

Type 2 diabetes (T2D) is a metabolic disease associated with cardiovascular dysfunction. The myocardium preferentially uses ketones over free fatty acids as a more energy-efficient substrate. The primary aim was to assess the effects of ketone monoester (K_me) ingestion on cardiac output index ([Formula: see text]i). The secondary aims were to assess the effects of K_me ingestion on markers of cardiac hemodynamics, muscle oxygenation, and vascular function at rest, during and following step-incremental cycling. We undertook a double-blind, randomized, crossover design study in 13 adults [age, 66 ± 10 yr; body mass index (BMI), 31.3 ± 7.0 kg·m^-2] with T2D. Participants completed two conditions, where they ingested a K_me (0.115 g·kg^-1) or a placebo taste-matched drink. Cardiac function was measured using thoracic impedance cardiography, and muscle oxygenation of the calf was determined via near-infrared spectroscopy. Macrovascular endothelial function was measured by flow-mediated dilation (FMD), and microvascular endothelial function was measured via transdermal delivery of acetylcholine (ACh) and insulin. Circulating β-hydroxybutyrate [β-Hb] was measured throughout. K_me ingestion raised circulating β-Hb throughout the protocol (peak 1.9 mM; P = 0.001 vs. placebo). K_me ingestion increased [Formula: see text]i by 0.75 ± 0.5 L·min^-1·m^-2 (P = 0.003), stroke volume index by 7.2 ± 4.5 mL·m^-2 (P = 0.001), and peripheral muscle oxygenation by 9.9 ± 7.1% (P = 0.001) and reduced systemic vascular resistance index by -420 ± -225 dyn·s^-1·cm^-5·m^-2 (P = 0.031) compared with the placebo condition. There were no differences between K_me and placebo in heart rate (P = 0.995), FMD (P = 0.542), ACh max (P = 0.800), and insulin max (P = 0.242). Ingestion of K_me improved [Formula: see text], stroke volume index, and peripheral muscle oxygenation but did not alter macro- or microvascular endothelial function in people with T2D.NEW & NOTEWORTHY For the first time, we show that acute ketone monoester ingestion (K_me) can increase cardiac output and stroke volume and reduce systemic vascular resistance at rest and during exercise in sodium glucose transporter inhibitors naïve (i.e. no drug-induced ketosis) people with type 2 diabetes. Acute K_me ingestion improves peripheral skeletal muscle oxygenation during moderate intensity and maximal exercise. K_me has no effect on macro- or microvascular endothelial function in people with type 2 diabetes.

Peripheral endothelial function, which accounts for the variability in shear stimulus, can be assessed using shear-mediated dilation normalized to the increased shear stimulus. Similarly, shear-mediated dilation of the internal carotid artery (ICA), an index of cerebrovascular endothelial function, should be normalized to increased shear stimulus. However, this approach has not yet been validated. Thus, the shear-mediated dilation of the ICA was assessed in 14 young adults during three levels of transient hypercapnia, induced by elevating the partial pressure of end-tidal carbon dioxide for 30 s by 6, 9, and 12 mmHg. The ICA shear rate (SR) was calculated using the ICA diameter and velocity, both measured by Doppler ultrasound. The total vasodilator stimulus was quantified as the SR area under the curve from the onset of hypercapnia to peak dilation, including and excluding baseline values [(SR_AUC) and delta SR_AUC (_DSR_AUC), respectively]. Shear-mediated dilation was calculated as the percent increase in diameter from baselines. ICA dilation was positively associated with _DSR_AUC [r_(rm) = 0.47, P < 0.01] but not with SR_AUC [r_(rm) = 0.32, P = 0.09]. Consequently, ICA dilation normalized to _DSR_AUC did not differ among trials (main effect of rial, P = 0.77). Contrarily, the difference in ICA dilation among trials remained significant when normalized to SR_AUC (main effect of trial, P = 0.02). Therefore, normalized shear-mediated dilation using _DSR_AUC can reduce variability associated with increased shear stimulus during ICA dilation assessment, thereby enhancing the validity of evaluating cerebrovascular endothelial function.NEW & NOTEWORTHY This study demonstrated that shear-mediated dilation of the internal carotid artery (ICA), an index of cerebrovascular endothelial function, increased with the increase of shear stimulus induced by different degrees of transient hypercapnia. However, when ICA dilation was normalized to the total increased shear stimulus above baseline, the vasodilation became comparable across different hypercapnia levels. Thus, normalizing ICA dilation to the total shear stimulus increased from baseline may enhance the validity of assessing cerebrovascular endothelial function.

The compliant nature of cerebral blood vessels may represent an important mechanical protection for sustained cerebral perfusion during reductions in arterial blood pressure (ABP). However, whether the rise in cerebrovascular compliance (Ci) with falling ABP persists and exhibits a threshold effect remains unknown. Therefore, we analyzed Ci changes during graded head-up tilt (HUT) in individuals with autonomic failure (AF), a group that tolerates graded and progressive reductions in ABP. Finger ABP and middle cerebral artery blood velocity (MCAv) were recorded from five patients with AF (61 ± 22 yr) at supine rest and during graded HUT. Tilt gradients increased incrementally between 30, 45, and 60° every 5 min until ABP reached a critically low value. The total time in HUT was 11 ± 4 min. Every 5 s during supine and HUT, individual ABP and MCAv waveforms were assessed for Ci and cerebrovascular resistance (CVR) using a modified Windkessel model. Pulse pressure (PP) was calculated as systolic ABP - diastolic ABP. A threshold value for the increase in Ci was determined using breakpoint analysis of the linear relationship between changes in Ci and PP or ABP across tilt periods. Graded HUT resulted in reduced ABP, PP, CVR, and mean MCAv, and increased Ci (all P < 0.01). Ci began to increase progressively after PP fell by 22 ± 6 mmHg and ABP fell by 20 ± 11 mmHg. In conclusion, the increase in Ci during progressive hypotension exhibited a threshold effect and persisted as ABP continued to fall.NEW & NOTEWORTHY We identify a threshold effect for the increase in cerebrovascular compliance (Ci) during progressive hypotension (baseline vs. end-tilt: 86 ± 18 vs. 50 ± 8 mmHg) in individuals with autonomic failure, such that Ci began to increase progressively after pulse pressure fell by 22 ± 6 mmHg and arterial blood pressure fell by 20 ± 11 mmHg.

Disruption of the blood supply to a limb in conjunction with active movement boosts muscle growth, aids in rehabilitation, and allows controlled exploration of the sensorimotor system. Yet, the underlying neuromechanical changes have not been observed in great detail. This study aims to report the acute neuromuscular effects of temporary blood flow restriction (BFR) through behavioral changes at the level of motor units (MUs) using high-density surface electromyography on the abductor digiti minimi muscle during 20 trapezoidal and sinusoidal isometric force tracking tasks (5 pre-BFR, 5 during BFR, and 10 post-BFR). Unsurprisingly, during BFR, reported discomfort levels increased significantly (ρ < 0.001) regardless of the task (+239% trapezoidal, +228% sinusoidal). However, BFR had very little impact on task tracking performance, though the reconstructed force derived from the underlying neural drive (smoothed cumulative spike train of MUs) deviated substantially during BFR (-40% in trapezoidal, -47% in sinusoidal). Regardless of the condition, the numbers of extracted MUs were consistent (20-26 in trapezoidal, 23-29 in sinusoidal). Interestingly, the interspike interval (ISI) of these units increased by 28% in trapezoidal and 24% in sinusoidal tasks during BFR, with ISI steadily returning to original values post-BFR. These results indicate that acute BFR transiently alters the active MU pool, and MU firing behavior, yet only slightly affects the resulting task performance. However, pre-BFR motor function is gradually restored after BFR release. These findings provide insights into the resulting effects of acute BFR administration and the complex response it elicits from the sensorimotor system.NEW & NOTEWORTHY To improve our understanding of how acute blood flow restriction (BFR) intervention affects neuromechanical function and motor unit characteristics, we applied high-density surface electromyography on the abductor digiti minimi muscle during isometric trapezoidal and sinusoidal precision force tracking tasks. Although BFR increased discomfort, it minimally affected force tracking performance; however, it did alter the underlying motor unit behavior. These findings further enhance our understanding of the neural mechanisms underlying BFR.

Remote ischemic preconditioning (RIPC) is a therapy characterized by repeated bouts of limb ischemia and reperfusion. RIPC protects against ischemia-reperfusion injury (IRI), and preclinical studies suggest that this is mediated through the release of endogenous opioids. We aimed to interrogate the role of endogenous opioids in RIPC-signaling in humans, using an arm model of IRI. We hypothesized that RIPC would attenuate IRI-induced reductions in brachial artery flow-mediated dilation (FMD) and that this would be prevented by systemic opioid receptor blockade. Eleven healthy adults (8 M/3 F, age = 28 ± 8 yr) completed three experimental visits in which IRI was induced via 20-min upper arm ischemia and 20-min reperfusion achieved via upper arm cuff inflation to 250 mmHg. FMD was measured at rest and again following IRI. During the control condition, RIPC was not performed. During the RIPC condition, RIPC was performed on the contralateral arm via four cycles of 5-min cuff inflation (250 mmHg) with 5-min reperfusion. During the opioid receptor blockade condition (naloxone), RIPC was performed in the presence of systemic opioid receptor blockade via intranasal naloxone (4 mg), which was administered during the first 5-min cycle of RIPC. The change in FMD from baseline versus post-IRI was compared between visits via a two-way repeated measures ANOVA (factor 1: time, factor 2: condition) followed by Tukey post hoc tests. IRI reduced FMD during the control (pre = 6.1 ± 2.4%, post = 3.5 ± 2.8%, P < 0.001) and naloxone (pre = 6.6 ± 2.7%, post = 3.5 ± 1.9%, P < 0.001) conditions but not during the RIPC condition (pre = 5.9 ± 2.2%, post = 4.9 ± 2.8%, P = 0.14). These findings demonstrate that RIPC provides vascular protection from IRI in humans through an opioid-dependent mechanism.NEW & NOTEWORTHY Remote ischemic preconditioning (RIPC) is a cardioprotective therapy characterized by brief cycles of limb ischemia and reperfusion. We demonstrate that a single bout of arm RIPC provides protection from ischemia-reperfusion injury-induced reductions in vascular function in healthy adults. This protection was attenuated when RIPC was administered in the presence of systemic opioid-receptor blockade via intranasal naloxone. These findings suggest that endogenous opioids contribute to RIPC-induced protection of vascular function in humans.

The mechanism of fibrosis at the patella-patellar tendon junction (PPTJ) was investigated using a rabbit overuse jumping model. Thirty-two female New Zealand White rabbits were randomly divided into control and jumping groups, and each group was further divided into four groups at 2, 4, 6, and 8 wk. The rabbit in the jumping group jumped 150 times/day, 5 days/wk. The PPTJ was removed at the corresponding time point and subjected to hematoxylin and eosin, safranin O, and immunohistochemical staining. Significant differences were observed in histological changes and fibrosis-related factors between the jumping and control groups (P < 0.01). Comparison within the jumping group indicated that the changes in the fibrocartilage zone thickness and proteoglycan area were pronounced at week 6; the expressions of transforming growth factor β (TGF-β1), Smad3, CTGF, α-SMA, COL-I, and COL-III peaked at week 6 (P < 0.05). The jumping load can lead to morphological and fibrotic changes in the patella-patellar tendon junction, with peak changes occurring at week 6. The fibrosis in the patella-patellar tendon junction may be associated with increased secretion of TGF-β1 and Smad3 due to jump loading, which upregulates CTGF expression and thus promotes the synthesis of α-SMA, COL-I, and COL-III.NEW & NOTEWORTHY The temporal pattern of fibrosis in the patella-patellar tendon junction (PPTJ) was determined by observing changes in histology and fibrosis-related factors at different time points in an overused jumping rabbit model. The results revealed that 1) the peak fibrotic changes in the PPTJ occurred at week 6 of jump training; 2) fibrosis in PPTJ may be associated with the changes in TGF-β1/Smad3. This study contributes to the development of targeted early interventions.

The respiratory control system exhibits neural plasticity, adjusting future ventilatory responses based on experience. We tested the hypothesis that ventilatory long-term facilitation induced by hypercapnic acute intermittent hypoxia (AIH) at rest enhances subsequent ventilatory responses to steady-state exercise. Fourteen healthy adults (age = 27 ± 5 yr; 7 males) participated in the study. On day 1, pulmonary function testing was performed. On days 2 and 3, in a pseudorandomized counterbalanced order, participants were exposed to AIH or Sham; AIH consisted of 15, 1-min hypoxic episodes with 1.5-min room air intervals. Mild hypercapnia (end-tidal Pco₂ clamped ∼3 mmHg above baseline) was sustained throughout AIH and Sham and for 40 min after. Approximately 20-30 min later, participants performed continuous mild to moderate constant-load cycle exercise in room air at 30, 60, and 90 W for 5 min each. Inspired minute ventilation (V̇i) increased by 3.6 ± 1.2 L·min^-1 after AIH versus baseline and was significantly greater than Sham (P = 0.013), signifying the onset of ventilatory long-term facilitation. Although V̇i during subsequent steady-state exercise was not significantly different between AIH and Sham (P = 0.511), the slope of the relationship between V̇i and CO₂ production rate (i.e., the system gain) and the calculated feedforward exercise gain were significantly increased (P = 0.021 and P < 0.001, respectively). Consequently, end-tidal Pco₂ was regulated ∼1 mmHg lower across all exercise workloads after AIH versus Sham (P = 0.006). Thus, ventilatory plasticity induced at rest alters future ventilatory responses to mild or moderate steady-state exercise.NEW & NOTEWORTHY We demonstrate that by inducing ventilatory long-term facilitation (LTF) at rest, subsequent ventilatory responses to mild or moderate exercise are altered. When ventilatory LTF was induced via hypercapnic acute intermittent hypoxia, the feedforward contribution to exercise hyperpnea increased, accompanied by marginal increases in the overall system response and decreases in end-tidal Pco₂. Thus, respiratory motor plasticity at rest can "spill over" to other physiological states, including mild or moderate steady-state exercise.

There is growing interest in understanding the complex relationship between psychosocial stress and the human gastrointestinal microbiome (GIM). This review explores the potential physiological pathways connecting these two and how they contribute to a proinflammatory environment that can lead to the development and progression of the disease. Exposure to psychosocial stress triggers the activation of the sympathetic nervous system (SNS) and hypothalamic-pituitary axis (HPA), leading to various physiological responses essential for survival and coping with the stressor. However, chronic stress in susceptible individuals could cause sustained activation of HPA and SNS, leading to immune dysregulation consisting of redistribution of natural killer (NK) cells in the bloodstream, decreased function of T and B cells, and elevation of proinflammatory cytokines such as interleukin-1, interleukin-6, tumor necrotic factor-α, interferon-gamma. It also leads to disruption of the GIM composition and increased intestinal barrier permeability, contributing to GIM dysbiosis. The GIM dysbiosis and elevated cytokines can lead to reciprocal effects and further stimulate the HPA and SNS, creating a positive feedback loop that results in a proinflammatory state underlying the pathogenesis and progression of stress-associated cardiovascular, gastrointestinal, autoimmune, and psychiatric disorders. Understanding these relationships is critical for developing new strategies for managing stress-related health disorders.

High cardiorespiratory fitness (CRF) is associated with reduced cortical thinning and gray matter (GM) shrinkage in older adults. We investigated associations of CRF measured with peak oxygen consumption (V̇o_2peak) with cortical thickness and GM volume across the adult lifespan. We hypothesized that higher CRF is associated with less cortical thinning and GM shrinkage across the adult lifespan, which is associated with better cognitive performance. This cross-sectional study recruited 172 sedentary yet healthy adults (65% women, 22-81 yr) who underwent treadmill exercise testing to measure V̇o_2peak, structural magnetic resonance imaging to assess cortical thickness and GM volume, and a comprehensive cognitive test battery to assess fluid cognitive function. Linear regression models were used to examine the associations of total and regional cortical thickness and GM volume with age, V̇o_2peak, and age × V̇o_2peak interaction after adjusting for sex, education, and total intracranial volume, and the associations of cortical thickness and GM volume with fluid cognitive performance. Mean and regional cortical thickness and total GM volume were associated negatively with age, whereas no associations were observed with V̇o_2peak. However, a significant interaction between age and V̇o_2peak on the right superior parietal volume indicated that aging was associated with smaller right superior parietal volume in the lower CRF group, whereas no association was observed in the higher CRF group. Larger right superior parietal volume was associated with better fluid cognitive performance. These findings highlight the importance of maintaining CRF to prevent or slow brain aging from an adult lifespan perspective.NEW & NOTEWORTHY High cardiorespiratory fitness may mitigate regional gray matter shrinkage across the adult lifespan.

We examined the effect of habitual preexercise caffeine supplementation on training-induced adaptations to exercising systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse pressure (PP), heart rate (HR), and double product (DP). Young women (means ± SD; 24 ± 7 yr) were randomized to a caffeine (120 mg) supplement (CAF; n = 17) or placebo (PLA; n = 16) group, completed 6 wk of high-intensity exercise training on three nonconsecutive days per week, and supplemented with CAF or PLA 30-60 min before exercise or else upon waking. Before (PRE) and after (POST) the intervention, SBP, DBP, and HR were measured and PP and DP were calculated, at rest and during fixed-power exercise at 50 and 75 W. Statistical analyses included three-way mixed-factorial ANOVAs with post hoc comparisons as necessary. Group × intensity × time interactions were observed for SBP (P = 0.0105) and DP (P = 0.003). SBP and DP increased with increasing exercise intensity at PRE and POST in both groups. However, although SBP and DP decreased PRE to POST at 50 and 75 W in PLA, SBP and DP did not change at any intensity from PRE to POST in CAF. An intensity × time interaction was observed for DBP (P = 0.006) indicating no change in resting DBP, but reductions from PRE to POST at 50 and 75 W that were independent of group. Main effects of intensity (P < 0.0001) and time (P = 0.03) were observed for HR, and a main effect of intensity was observed for PP (P < 0.0001). Habitual caffeine supplementation blunted training-induced reductions in exercising SBP and DP. Individuals may wish to avoid preexercise supplementation if seeking to maximize the BP-lowering benefits of exercise.NEW & NOTEWORTHY Habitual preexercise caffeine consumption prevented reductions in exercising systolic blood pressure and double product induced by 6 wk of high-intensity exercise in women. Therefore, our findings indicate that habitual preexercise caffeine supplementation may impede beneficial hemodynamic adaptations of exercise training in healthy, young women.