Experimental Physiology最新文献

The differential Fick method is well established for measuring effective pulmonary blood flow (EPBF) and cardiac output (CO) but until now it has only been used for patients on mechanical ventilation. Here we present and evaluate a new approach adapted to spontaneous breathing situations. Ten healthy subjects with diverse anthropometric and respiratory parameters were studied in the sitting position. Rebreathing through a dead space of precisely known volume and recording the resulting rise in the end-tidal CO₂ value allowed the determination of EPBF. The shunted blood flow fraction was estimated from the arterial oxygen saturation to obtain cardiac output (FickCO). Two measurements were made on each subject 15 min apart. Reference values for cardiac output (RefCO), were calculated as the product of stroke volume and heart rate where the stroke volume was measured with established echocardiography techniques. Heart rate and arterial oxygen saturation were measured with an ordinary pulse oximeter. Comparing FickCO to RefCO using a Bland-Altman analysis, we obtained a mean bias of 0.03 L/min, limits of agreement (LoA) of +1.43 to -1.37 (95% CI) L/min and a percentage error (PE) of 0.25. For the mean of two FickCO observations, we obtained a mean bias of -0.04 L/min, LoA +0.94 to -1.01 (95% CI) and PE of 0.17. The differential Fick method can be adapted to spontaneously breathing situations with good absolute accuracy using simple equipment. Short data collection times make it possible to use the mean of repeated observations and thereby get adequate precision. The new method could therefore be of value both in the pre-operative and the post-operative setting.

High-altitude training is widely adopted by endurance athletes with the aim of increasing total haemoglobin mass (tHb_mass) and thereby endurance exercise performance. However, divergent effects on tHb_mass and exercise performance have been reported in athletes commencing altitude camps with initial high baseline levels for tHb_mass, questioning the efficacy of in-season interventions in elite athletes. Therefore, haematological adaptations and exercise performance were evaluated in 12 elite cyclists completing an in-season 'Live High-Train High' (LHTH) altitude camp (21 days at 3000 m) immediately after participating in the national championships. Additionally, for seven participants, we compared haematological and exercise performance effects with an off-season heat acclimation training (HEAT) intervention (six 1-h sessions per week for 5 weeks). The LHTH resulted in a 3.5 ± 2.0% (P < 0.001, n = 12) increase in tHb_mass, with decay to Pre levels 10 days after returning to sea-level. For participants followed for 9 months, the tHb_mass effect was comparable to that of the off-season HEAT intervention (5.4 ± 3.9% for HEAT, LHTH vs. HEAT: P = 0.801, n = 7) and baseline levels prior to the interventions were almost identical (965 g Pre-HEAT vs. 960 g Pre-LHTH). Exercise performance and maximal oxygen uptake, tested immediately (2-3 days) and 10 days after LHTH, were not improved, and individual changes were not correlated to any of the haematological parameters assessed. In conclusion, the in-season LHTH training camp effectively increased tHb_mass in elite cyclists; however, there was a rapid decay in tHb_mass upon return to sea-level and no effect on exercise performance.

Acute intermittent hypoxia (AIH) can increase maximal strength of limb muscles in people with incomplete spinal cord injury (SCI), but it is mostly untested in people without SCI. Acute intermittent hypercapnia (AIC) may engage similar respiratory circuits to AIH, but the effects of AIC on human limb motor output are unknown. We examined whether single sessions of AIH or AIC improved motor output to a hand muscle in neurologically intact people. Twelve adults completed a single 30-min session of AIH (breathing alternate 1-min low oxygen air and 1-min normal air), AIC (alternate 1-min high carbon dioxide air and 1-min normal air), or SHAM (normal air). At baseline and for 80 min post-intervention, participants performed repeated isometric maximal voluntary thumb adductions. Transcranial magnetic stimulation elicited motor evoked potentials (MEPs) from first dorsal interosseous and adductor pollicis at each time point. Generalised linear mixed models were compared between conditions (AIH, AIC, SHAM). Normalised to baseline, voluntary activation was higher after AIC than SHAM (5.9%, P < 0.001) and AIH (5.5%, P < 0.001); MVC force was higher after AIC than SHAM (7.7%, P < 0.001), whereas maximal EMG was higher after AIH than SHAM (14.3%, P < 0.001). MEPs and maximal M-waves did not differ between conditions for either muscle (P > 0.25). Thus, single sessions of AIC induced small motor output improvements in people without SCI, but AIH did not. AIC increased maximal voluntary activation, but the mechanisms for this remain unclear because the MEPs provided no evidence for corticospinal facilitation.

Following an acute infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a substantial percentage of patients report the persistence of debilitating symptoms, often grouped in a syndrome termed 'long COVID'. We sought to identify potential pathophysiological mechanisms responsible for the persistence, in some long COVID patients, of symptoms related to fatigue/exercise intolerance (excessive or early fatigue, excessive or early dyspnoea, muscle weakness, and myalgias) more than 2 years after the original infection. Twelve patients who reported persistent symptoms (Long COVID group; 57 ± 6 years, mean ± SD), and 14 patients without the symptoms (Control group; 57 ± 8 years) were evaluated. An extensive series of measurements were performed to identify pathophysiological mechanisms potentially responsible for the symptoms. In long COVID patients, all items evaluating quality of life (SF-36 questionnaire) had lower scores (P < 0.01) compared to control. The habitual level of physical activity, muscle size and strength, maximal aerobic power and the ventilatory thresholds, peak cardiac function, the mechanical efficiency of cycling, pulmonary ${\dot{V}}_{O_2}$ kinetics, microvascular/endothelial function (hyperemic response in the common femoral artery during passive leg movements), skeletal muscle oxidative metabolism (peak fractional O₂ extraction and muscle ${\dot{V}}_{O_2}$ recovery kinetics by the repeated occlusions test, by near-infrared spectroscopy) were not different in the two groups. Evidence of ventilatory inefficiency was described in a subgroup of long COVID patients. More than 2 years after the original SARS-CoV-2 infection, a discrepancy was observed between the persistence of debilitating symptoms of fatigue/exercise intolerance and the absence of several investigated pathophysiological mechanisms. The discrepancy may be due to factors that remain to be elucidated.

Ouabain-induced hypertension is a multifactorial and condition-dependent phenomenon involving coordinated actions across vascular, renal and central nervous system pathways. At the vascular level, ouabain inhibits Na⁺/K⁺-ATPase, particularly the α2-isoform, leading to elevated intracellular Ca²⁺, enhanced vasoconstriction and structural remodelling of resistance arteries. These effects are exacerbated by oxidative stress, inflammation, and altered expression of Ca²⁺-mobilizing proteins such as NCX1 and TRPC channels. In the kidney, ouabain disrupts Na⁺ handling, especially in the proximal tubule, suppresses natriuretic pathways like the D1 dopamine receptor, and promotes volume expansion through renal and sympathetic mechanisms. Centrally, ouabain acts on sodium-sensitive brain regions, including the median preoptic nucleus, rostral ventrolateral medulla and paraventricular nucleus, where it increases sympathetic outflow and impairs baroreflex control. These effects are potentiated by local interactions with brain-derived angiotensin II and cerebrospinal Na⁺, independent of peripheral ouabain levels. However, the hypertensive response is not universal and may vary by strain, salt status, genetic background and experimental conditions. These insights carry important translational implications. Elevated levels of endogenous ouabain (EO) have been identified in patients with salt-sensitive, low-renin or neurogenic hypertension. Therapeutic strategies targeting ouabain-sensitive pathways include isoform-selective Na⁺/K⁺-ATPase modulators, NCX or TRPC inhibitors, and agents acting on the central renin-angiotensin system. EO-neutralizing therapies such as digoxin antibodies may also hold clinical promise. Personalized medicine approaches incorporating EO sensitivity markers and genotype-specific models may advance the management of resistant hypertension and deepen our understanding of ouabain's dual role as both physiological modulator and pathological trigger.

Acute myocardial infarction is a leading cause of morbidity and mortality, with ischaemia-reperfusion (I/R) injury exacerbating myocardial damage. Vagus nerve stimulation (VNS) has been reported to exert cardioprotective effects, but its efficacy in preconditioning against I/R injury requires further investigation. We evaluated the cardioprotective effects of VNS preconditioning in a rat model of acute myocardial infarction with induced I/R injury. Sixty rats were randomized into Pre-VNS, Control and Sham groups. The Pre-VNS group received 1 week of low-level cervical VNS before induction of I/R injury; stimulation was deactivated 30 min before ischaemia. Survival, echocardiographic function, reperfusion arrhythmias, arrhythmia inducibility, infarct size, apoptosis and inflammatory cytokines were assessed. Survival did not differ significantly between Pre-VNS and Control groups (75.0% vs. 65.0%, p = 0.497). However, Pre-VNS animals exhibited preserved cardiac function, with higher ejection fraction and fractional shortening (p < 0.001). VNS preconditioning reduced the incidence of reperfusion arrhythmia during left anterior descending coronary artery ligature release (p = 0.006) and decreased the arrhythmia index on programmed stimulation (p = 0.003). Infarct size and cardiomyocyte apoptosis were significantly attenuated (p < 0.001), accompanied by markedly lower serum interleukin-1β, interleukin-6 and tumour necrosis factor-alpha levels (p < 0.001). VNS preconditioning effectively mitigates I/R injury by improving cardiac function, reducing infarct size and arrhythmias, and attenuating inflammatory and apoptotic responses.

Trimethylamine N-oxide (TMAO) is linked to arterial stiffness and atherosclerosis. Cardiovascular disease (CVD) risk increases following menopause in women. Whether menopause influences plasma TMAO metabolism to mediate CVD risk is unknown. Women with obesity were classified as premenopausal (n = 13; 40.3 ± 2.7 years; 39.4 ± 2.0 kg/m²) or postmenopausal (n = 22; 56.5 ± 1.1 years; 35.6 ± 0.9 kg/m²) via self-reported presence/absence of menses (last 12 months). Men were age- and body mass index-matched to postmenopausal women (n = 16; 55.9 ± 2.1 years; 34.3 ± 1.2 kg/m²) as controls to discern potential menopause-driven TMAO differences. Carotid-femoral pulse wave velocity (cfPWV) and pulse wave analysis (applanation tonometry) were analysed to assess arterial stiffness, aortic waveforms and blood pressure. Fasting plasma TMAO and precursors (carnitine, choline, betaine and trimethylamine (TMA)) were assessed (mass spectroscopy). A 180 min 75 g oral glucose tolerance test was performed to approximate insulin sensitivity and quantify vascular cell (vascular cell adhesion molecule 1 (VCAM-1)) and intercellular adhesion molecules (intercellular adhesion molecule 1 (ICAM-1)). Body composition (DXA/BodPod) and fitness ( ${\dot{V}}_{O_2\mathrm{peak}}$ ) were measured. Premenopausal women were younger than men and postmenopausal women (P < 0.0001, η² = 2.29). Men had lower body fat (P = 0.001, η² = 0.80) and higher fat-free mass (P = 0.004, η² = 0.42) compared to both pre- and postmenopausal women. There were no differences among groups in fitness, insulin sensitivity, ICAM-1 or blood pressure (P > 0.05), but men had higher cfPWV (P = 0.040, η² = 0.27) and VCAM-1 (P = 0.041, η² = 0.32). Postmenopausal women had elevated TMAO (P = 0.040, η² = 0.29), compared with men and premenopausal women, yet men had elevated TMA (P = 0.041, η² = 0.17), carnitine (P = 0.003, η² = 0.27), choline (P = 0.022, η² = 0.35) and betaine (P < 0.0001, η² = 0.59). Thus when taken together, menopause may raise TMAO in women, while older men appear to have unique TMAO precursor metabolism linked to CVD risk.

High-resolution movement data from Cuvier's beaked, or goose-beaked whale (Ziphius cavirostris, hereafter Ziphius, n = 8) tag deployments (4.1-19.2 days) were used to estimate blood and tissue O₂ and CO₂ levels. Acceleration and magnetometry data were used to estimate the locomotion cost (LC) from the relationship between activity and the O₂ consumption rate. We estimated that the diving metabolic rate (DMR) decreased with increasing dive duration, ranging from 6.18 mL O₂ min^-1 kg^-1 for very short dives (<1.0 min) to 1.65 mL O₂ min^-1 kg^-1 and 2.06 mL O₂ min^-1 kg^-1 for intermediate (>17.5 and ≤33.3 min) and long dives (>33.3 min), respectively. The calculated aerobic dive limit (cADL), average behavioural ADL (bADL) and dynamic ADL (dADL) were 62.4, 61.3 (44.3-75.4) and 41.7 (2.0-102.5) min, respectively. Despite the physiological and metabolic adjustments assumed by the model, the muscle O₂ ran out for many of the stereotypical long, deep dives exhibited by these animals. Based on the model results, we speculate that a large portion of the foraging dives in Ziphius are fuelled by alternative metabolic pathways, for example, phosphocreatine or glycolysis. A reliance on these alternative metabolic pathways during foraging may require long recovery periods, including primarily aerobic dives. Disturbing this normal dive pattern may disrupt this normal dive pattern, leading to behavioural and physiological changes that could cause trauma.

Magnetophosphenes are flickering lights perceived when an extremely low frequency magnetic field generates a sufficiently strong electric field in the head. Understanding how phosphenes are produced is crucial, as they form the basis for international safety standards and guidelines for both workers and the general population. However, there is still ongoing debate about whether this phenomenon originates in the retina, the cortex, or involves both. Investigating magnetophosphenes at various frequencies during dark adaptation provides deeper physiological insights into this process. Forty-one participants were exposed to varying levels of magnetic stimulation using a custom global transcranial alternative magnetic stimulation system that provided full-head exposure. Participants were divided into four groups: one light-exposed group and three dark-adapted groups, each assigned a different frequency (20, 50 and 60 Hz). Every 3 min during a 42-min dark adaptation period, participants reported their threshold for magnetophosphene perception. Flux density thresholds were then compared across groups using repeated measures ANOVAs. The data acquired showed a significant (F(15, 270) = 3.637, P < 0.001) increase in the magnetophosphene threshold throughout the 42-min darkness adaptation period. An inversed exponential decay regression was used to model the time course of the magnetophosphene threshold for each frequency. The rising magnetophosphene threshold during dark adaptation is likely linked to retinal phototransduction mechanisms, suggesting that magnetophosphene perception originates from rod cells in the retina. In addition to their significance for establishing new international guidelines and safety standards for workers and the public, our findings could also pave the way for new research into non-invasive assessments of retinal dysfunction.