Experimental Physiology最新文献

Endurance exercise is associated with increased life duration and improved life quality. Paradoxically, high exercise intensity is also associated with increased coronary artery calcification (CAC) and a small but significant increased risk of adverse cardiac events during exercise. The mechanisms underlying the development of CAC during prolonged high-intensity endurance exercise are unknown. This study aims to determine if there are differences in cardiovascular haemodynamic measures and heart rate variability (HRV) in individuals with (CAC⁺) and without CAC (CAC^-). Hemodynamic measures from 56 healthy, middle-aged (median [interquartile range] 51 [43-58] years) individuals (41 men/15 women) participating in a 91 km [251.2 [217.2-271.6] min] leisure sport mountain bike race were included in this study. Twenty-five participants (20 men/5 women) were classified as CAC⁺ based on coronary computed tomographic assessment. Haemodynamic measures and HRV were quantified at the top of the hardest hill (THH) during the last quarter of the race. At the top of THH, CAC⁺ individuals had significantly higher systolic blood pressure (SBP) (235 [225-245] mmHg vs. 220 [193-238] mmHg, P = 0.008), higher diastolic blood pressure (DBP) (105 [95-110] mmHg vs. 95 [85-110] mmHg, P = 0.006), higher pulse pressure (130 [125-140] mmHg vs. 123 [110-130] mmHg, P = 0.039), higher mean rate pressure product (33,882 [30,872-35,053] bpm × mmHg vs. 31,028 [27,392-33,047] bpm × mmHg, P = 0.028), and larger increase in DBP from baseline (20 [20-30] mmHg vs. 10 [0-20] mmHg, P = 0.001), compared with CAC^- individuals. Further, CAC⁺ participants showed a significant reduction in the low-frequency component of HRV (HRV_LF) (6.3 [2.4-11.5] ms² vs. 12.4 [6.8-20.2] ms², P = 0.044). In multivariable analysis, HRV_LF was an independent predictor of the presence of CAC even after adjusting for established risk factors of atherosclerosis: age, sex, body mass index, maximum heart rate, ${\dot{V}}_{O_2\max }$ , smoking, resting SBP and resting DBP. CAC⁺ individuals had significant alterations in haemodynamic measures and HRV_LF following prolonged high-intensity endurance exercise compared with individuals without CAC. HRV_LF was an independent predictor of CAC, suggesting an adverse autonomic response to high-intensity endurance exercise in individuals with CAC.

The impact of housing temperature on exercise-induced metabolic adaptations is not well understood, despite extensive research on the benefits of exercise for metabolic health. The aim of this study was to elucidate how housing temperatures influence the molecular responses and metabolic benefits of exercise in mice. Male C57BL/6N mice were housed at either room temperature (RT, 21°C) or in a thermoneutral environment (TN, 29°C) and subjected to either a 6-week or acute exercise regimen. The results demonstrated that chronic exercise in TN conditions significantly improved glucose tolerance, whereas no such improvement was observed in RT conditions. Exercise reduced adipocyte size in inguinal and epididymal white adipose tissue in RT conditions, but no significant exercise-induced browning of inguinal white adipose tissue was detected at either housing temperature. Additionally, housing temperature predominantly influenced key metabolic proteins in skeletal muscle, with exercise and temperature exhibiting interactive effects on glycogen synthase, Glut4 and Pgc-1α. Moreover, the regulation of exerkines, including Fgf21, fetuin-A, irisin, Gdf15, spexin and apelin, was temperature dependent after both long-term and acute exercise. Notably, expression of Metrnl was consistently upregulated in skeletal muscle after long-term exercise in both RT and TN environments, but was downregulated after acute exercise. These findings highlight that environmental temperature critically modulates the metabolic benefits of exercise and the expression of exerkines. The results of this study suggest that conventional RT conditions might obscure the full metabolic effects of exercise. We recommend the use of TN conditions in future research to reduce confounding factors and provide a more accurate assessment of the metabolic benefits of exercise.

Dynamic resistance exercise (RE) produces sinusoidal fluctuations in blood pressure, with hypotension and cerebral hypoperfusion commonly observed immediately following RE. Whether the cerebral vasculature adapts to these regular blood pressure challenges is unclear. This study examined the cerebrovascular response to post-dynamic RE orthostasis. RE-trained (n = 15, female = 4) and healthy untrained individuals (n = 15, female = 12) completed five stands: one after seated rest, with each of the subsequent four stands occurring immediately following a set of 10 repetitions of unilateral leg extension exercise at 60% of their one repetition maximum. Beat-to-beat blood pressure, mean middle cerebral artery blood velocity (MCAv_mean) and end-tidal carbon dioxide were measured throughout. During standing the mean arterial blood pressure (MAP) and MCAv_mean nadirs were identified. There was no difference between groups for age (mean ± SD, 26 ± 7 RE-trained vs. 25 ± 6 years untrained, P = 0.683) or weight (78 ± 15 vs. 71 ± 15 kg, P = 0.683). At MAP nadir during the post-exercise stand, a greater reduction in MAP was observed in the RE-trained group (e.g., set 4, -45 ± 11 vs. -36 ± 6 mmHg, training effect P = 0.026). However, post-exercise stand MCAv_mean at MCAv_mean nadir was not different (e.g., set 4, -20 ± 7 vs. -17 ± 6 cm/s, interaction effect P = 0.478). Rate of regulation was higher in the RE-trained group (set 1, 0.301 ± 0.170 vs. 0.167 ± 0.009, training effect P = 0.023). Despite RE-trained individuals demonstrating greater absolute reductions in MAP during orthostasis following RE, there were no differences in MCAv_mean, suggesting that habitual RE may mitigate post-exercise cerebral hypoperfusion.

Using proton magnetic resonance spectroscopy (¹H MRS) to determine total creatine (tCr) concentrations will become increasingly prevalent, as the role of creatine (Cr) in supporting brain health gains interest. Methodological limitations and margins of error in repeated ¹H MRS, which often surpass reported effects of supplementation, permeate existing literature. We examined the intra- and inter-session reliability and repeatability of ¹H MRS for determining tCr concentrations across multiple brain regions (midbrain, visual cortex and frontal cortex). Eighteen healthy adults aged 20-32 years were recruited (50% female; n = 14 intra-session; n = 15 inter-session). ¹H Magnetic resonance imaging and spectroscopy were completed at 3 T. Intra-session analyses involved repeated ¹H MRS of the midbrain, visual cortex and frontal cortex without participant or voxel repositioning, whereas inter-session analyses involved measurements of the same regions, but with participant and voxel repositioning between repeated measurements. The ¹H MRS data (174 spectra) were analysed using TARQUIN and OSPREY, and voxel fractions (grey/white matter and CSF) were determined using segmentation. Our findings show that tCr concentrations can be determined reliably and repeatably using ¹H MRS, within an error of <2%, and that large inter-regional differences in tCr concentration are present in the human brain. We provide new minimum detectable change data for tCr concentrations, a detailed discussion of the inherent error sources in repeated ¹H MRS, including the substantial effect of the analysis package on tCr quantification, and suggestions for how these should be managed to improve the interpretability and clinical value of future research. More studies are needed to determine whether our findings can be replicated in other centres and different populations.

Prior studies have investigated the efficacy of a single 1 min bout of stair-stepping on reducing postprandial blood glucose (BG) in the morning, but none have investigated this effect in the evening when glycaemic responses are larger due to circadian regulation and β-cell responsiveness. This work investigated the efficacy of a 1 min bout of self-selected, low-intensity stair-stepping performed in the evening on reducing the change from baseline to the 60 min time point postprandial BG. Thirty people (43% male, 29 (10) years) participated in a randomized crossover-controlled trial. Participants completed two separate evening trials following an oral glucose tolerance test (OGTT) (75 g of dextrose dissolved in water): (a) 0 min of stair-stepping seated control condition, and (b) 1 min of stair-stepping condition. One minute of stair-stepping attenuated the change from baseline to 60 min postprandial BG versus control condition (2.5 (2.8) vs. 4.3 (2.3) mmol/L (P < 0.001). Area under the curve (AUC) and incremental area under the curve (iAUC) were lower for the 1 min condition versus control (mean difference = -0.4,95% CI: 0.1-0.8 (P = 0.023) and (mean difference = -0.6, 95% CI 0.1-1.1 mmol/L^-1 min^-1 (P = 0.043), respectively. The modified BORG rate of perceived exertion scale showed participants perceived the exercise as light intensity (1.9 (1.1)). A single, 1 min bout of low-intensity stair stepping at a self-selected pace reduced evening postprandial BG levels following an OGTT in young non-diabetic adults.

Ischaemic heart disease remains a leading cause of premature mortality and morbidity. Understanding the associated pathophysiological mechanisms of cardiac dysfunction arising from ischaemic heart disease and the identification of sites for new therapeutic interventions requires a preclinical model that reproduces the key clinical characteristics of myocardial ischaemia, reperfusion and infarction. Here, we describe and validate a refined and minimally invasive translationally relevant approach to induce ischaemia, reperfusion and infarction in the sheep. The novelty and refinement in the procedure stems from utilization of implantable cardiac defibrillators prior to coronary engagement, balloon angioplasty to induce infarction, and intra-operative anti-arrhythmic drug protocols to reduce adverse arrhythmic events. The protocol is readily adoptable by researchers with access to standard fluoroscopic instrumentation, and it requires minimally invasive surgery. These refinements lead to a substantial reduction of intra-operative mortality to 6.7% from previously published values ranging between 13% and 43%. The model produces key characteristics associated with the fourth universal definition of myocardial infarction, including ECG changes, elevated cardiac biomarkers and cardiac wall motility defects. In conclusion, the model closely replicates the clinical paradigm of myocardial ischaemia, reperfusion and infarction in a translationally relevant large animal setting, and the applied refinements reduce the incidence of intra-operative mortality typically associated with preclinical myocardial infarction models.

The ability to regulate finger forces is critical for manipulating objects during everyday tasks but is impaired after damage to white matter tracts that transmit motor commands into the spinal cord. This study examines cortico-spinal connectivity required for force control by the digits after neurological injury. We report on a unique case of a stroke survivor who retained the ability to control finger forces at a level comparable to neurologically intact adults despite extensive loss of white matter volume and severely compromised transmission from cortical motor areas onto the final common pathway. Using a combination of imaging methods and noninvasive stimulation techniques, we illustrate the structure and function of a slow-conducting, cortico-spinal pathway minimally spared by stroke that underlies this stroke survivor's ability to transition and stabilize finger forces of the paretic hand during precision grip. We interpret findings in the context of physiological mechanisms underlying distal limb control and current thinking on neural adaptation after brain injury due to stroke.