Experimental Physiology最新文献

Heart failure represents a dynamic clinical challenge with the continuous rise of a multi-morbid and ageing population. Yet, the evolving nature of mechanical circulatory support offers a variety of means to manage candidates who might benefit from such interventions. This narrative review focuses on the role of the main mechanical circulatory support devices, such as ventricular assist device, extracorporeal membrane oxygenation, Impella and TandemHeart, in the physiological process of ventricular unloading and remodelling in heart failure, highlighting their characteristics, mechanism and clinical outcomes. The outcome measures described include physiological changes (i.e., stroke volume or preload and afterload), intracardiac pressure (i.e., end-diastolic pressure) and extracardiac pressure (i.e., pulmonary capillary wedge pressure). Overall, all the above mechanical circulatory support strategies can facilitate the unloading of the ventricular failure through different mechanisms, which subsequently affects the ventricular remodelling process. These physiological changes start immediately after ventricular assist device implantation. The devices are indicated in different but overlapping populations and operate in distinctive ways; yet, they have evidenced performance to a favourable standard to improve cardiac function in heart failure, although this proved variable for different devices, and further high-quality trials are vital to assess their clinical outcomes further. Both Impella and TandemHeart are indicated mainly in cardiogenic shock and high-risk percutaneous coronary intervention patients; at the time the literature was evaluated, both devices were found to yield a significant improvement in haemodynamics but not in survival. Nevertheless, the choice of device strategy should be based on individual patient factors, including indication, to optimize clinical outcomes.

Exercise intolerance and exertional dyspnoea are hallmarks of fibrosing interstitial lung disease (FILD) and are associated with worse prognosis and quality of life. Activation of pulmonary vagal afferents influences the ventilatory pattern and contributes to the sensation of dyspnoea. We tested the hypothesis that nebulized fentanyl, which might attenuate aberrant pulmonary afferent activity in FILD, reduces ventilation and dyspnoea while extending exercise endurance time (EET). In this randomized, single-blind, placebo-controlled study, eight FILD patients (two males, 71 ± 6 years of age) performed incremental cardiopulmonary cycle exercise tests following nebulization of either fentanyl citrate (100 µg) or 0.9% saline. Previous work indicated that this dose was unlikely to produce central effects. Comparisons between treatment conditions at rest were undertaken using Student's paired t-test, and exercise data were evaluated with two-way ANOVA with repeated measures. Dyspnoea was assessed using the Borg dyspnoea scale. Resting respiratory variables were not different following treatment with fentanyl and saline; however, resting heart rate was lower following fentanyl (P = 0.002) and remained lower throughout exercise compared with placebo (P = 0.008). Fentanyl did not increase EET (placebo 334 ± 117 s vs. fentanyl 348 ± 126 s, P = 0.250) although overall minute ventilation was reduced slightly (mean difference: -0.97 L/min, P = 0.022). There were no differences in ratings of dyspnoea intensity or unpleasantness between the conditions either at rest or at end-exercise. Nebulized fentanyl did not improve EET or exercise dyspnoea but did decrease minute ventilation during exercise, although the extent of this reduction appears clinically insignificant. These findings suggest that nebulized fentanyl is unlikely to offer significant benefits for enhancing exercise capacity in FILD.

In this review, we have amalgamated the literature, taking a multimodal neuroimaging approach to quantify the relationship between neuronal firing and haemodynamics during a task paradigm (i.e., neurovascular coupling response), while considering confounding physiological influences. Original research articles that used concurrent neuronal and haemodynamic quantification in humans (n ≥ 10) during a task paradigm were included from PubMed, Scopus, Web of Science, EMBASE and PsychINFO. Articles published before 31 July 2023 were considered for eligibility. Rapid screening was completed by the first author. Two authors completed the title/abstract and full-text screening. Article quality was assessed using a modified version of the National Institutes of Health Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. A total of 364 articles were included following title/abstract and full-text screening. The most common combination was EEG/functional MRI (68.7%), with cognitive (48.1%) and visual (27.5%) tasks being the most common. The majority of studies displayed an absence/minimal control of blood pressure, arterial gas concentrations and/or heart rate (92.9%), and only 1.3% monitored these factors. A minority of studies restricted or collected data pertaining to caffeine (7.4%), exercise (0.8%), food (0.5%), nicotine (2.7%), the menstrual cycle (0.3%) or cardiorespiratory fitness levels (0.5%). The cerebrovasculature is sensitive to numerous factors; thus, to understand the neurovascular coupling response fully, better control for confounding physiological influences of blood pressure and respiratory metrics is imperative during study-design formulation. Moreover, further work should continue to examine sex-based differences, the influence of sex steroid hormone concentrations and cardiorespiratory fitness.

The cardiac conduction system in large carnivores, such as the African lion (Panthera leo), represents a significant knowledge gap in both veterinary science and in cardiac electrophysiology. Short QT intervals have been reported from zoo-kept, anaesthetized lions, and our goal was to record the first ECGs from wild, conscious lions roaming freely, and compare them to zoo-kept lions under the hypothesis that short QT is unique to zoo-kept lions. Macroscopic and histological examinations were performed on heart tissue removed from nine healthy zoo lions. ECGs were recorded from the nine anaesthetized zoo-kept lions, and from 15 anaesthetized and conscious wild lions in Africa. Our histological and topographical description of the lion's heart matched what has previously been published. In conscious lions, the ECG recordings revealed a mean heart rate of 70 ± 4 beats/min, with faster heart rates during the night. PQ and QT intervals were heart rate dependent in the conscious lions. Interestingly, QT intervals recorded in wild lions were markedly longer than QT intervals from zoo lions (398 ± 40 vs. 297 ± 9 ms, respectively; P < 0.0001). Anaesthesia or heart rate did not account for this difference. We provide a comprehensive description of the cardiac anatomy and electrophysiology of wild and zoo-kept lions. QT intervals were significantly shorter in zoo lions, suggesting functional disparities in cardiac electrophysiology between wild and zoo-kept lions, potentially related to physical fitness. These findings underscore the plasticity of cardiac electrophysiology and may be of value when reintroducing endangered species into the wild and when managing lions in human care.

There are differences within the literature regarding the upper frequency cut-off point of the dynamic cerebral autoregulation (CA) high-pass filter. The projection pursuit regression approach has demonstrated that the upper frequency limit is ∼0.07 Hz, whereas another approach [transfer function analysis (TFA) phase approaching zero] indicated a theoretical upper frequency limit for the high-pass filter of 0.24 Hz. We investigated how these limits accurately represent the CA upper frequency limit, in addition to extending earlier findings with respect to biological sexes and across the cardiac cycle. Sixteen participants (nine females and seven males) performed repeated squat-stand manoeuvres at frequencies of 0.05, 0.10, 0.15, 0.20 and 0.25 Hz, with insonation of the middle and posterior cerebral arteries. Linear regression modelling with adjustment for sex and order of squat completion was used to compared TFA gain and phase with 0.25 Hz (above the theoretical limit of CA). The upper frequency limit of CA with TFA gain was within the range of 0.05-0.10 Hz, whereas TFA phase was within the range of 0.20-0.25 Hz, and consistent between vessels, between sexes and across the cardiac cycle. Females displayed greater middle cerebral artery gain compared with males (all P < 0.047), and no phase differences were present (all P > 0.072). Although sex-specific differences were present for specific TFA metrics at a given frequency, the upper frequency limit of autoregulation was similar between cerebral conduit vessels, cardiac cycle phase and biological sex. Future work is warranted to determine whether an upper frequency limit exists with respect to hysteresis analyses.

Younger women rely on altering cardiac output ( $\dot{Q}$ ) to regulate blood pressure (BP). In contrast, older women rely more on altering vascular tone. However, evidence suggests that the ability to alter systemic vascular conductance (SVC) is diminished in older women. In the present study, cardioselective β-blockade was utilized to diminish the relative contribution of $\dot{Q}$ to BP regulation and thereby evaluate age-related vascular limitations in women at rest and during large muscle dynamic exercise. Younger (n = 13, mean age 26.0 years) and older (n = 14, mean age 61.8 years) healthy women performed submaximal bouts of semi-recumbent cycling exercise at varying intensities while receiving an intravenous infusion of esmolol, a β₁-antagonist, or saline control in a repeated-measures crossover design. $\dot{Q}$ was attenuated during esmolol infusion, with greater reductions during exercise (moderate, -1.0 (95% CI, -1.6 to -0.5) L/min, P < 0.001; heavy, -2.0 (95% CI, -2.6 to -1.5) L/min, P < 0.001) than seated rest (-0.5 (95% CI, -1.1 to 0.0) L/min, P = 0.048), and this reduction was not significantly different between age groups (P = 0.122). Older women exhibited a greater attenuation in mean arterial pressure (MAP) during esmolol (-7 (95% CI, -9 to -4) mmHg, P < 0.001) relative to younger women (-2 (95% CI, -5 to 0) mmHg, P = 0.071). These changes coincided with a greater reduction of SVC in the younger women during esmolol (-15 (95% CI, -20 to -10) mL/min/mmHg, P < 0.001) compared to older women (-3 (95% CI, -9 to 2) mL/min/mmHg, P = 0.242). Together, these findings provide evidence that older, postmenopausal women have a diminished ability to adjust SVC in order to regulate MAP.

Mouse models are crucial for understanding pulmonary hypertension (PH) mechanisms and developing therapies, but existing mouse models under hypoxia only exhibit mild PH. To address this, we established a double-hit model combining unilateral pneumonectomy (LPx) or left pulmonary artery ligation (LPAL) with hypoxia exposure in C57BL/6 mice. Our detailed haemodynamic and histological evaluations post-surgery demonstrated pronounced elevations in right ventricular systolic pressure (RVSP) (LPAL: 41.1 ± 4.63 mmHg, P = 0.005; LPx: 38.4 ± 2.95 mmHg, P = 0.002; Sham: 32.1 ± 2.21 mmHg) and pulmonary vascular wall thickness (LPAL: 56.9 ± 3.34%, P = 0.02; LPx: 54.3 ± 4.65%, P = 0.04; Sham: 44.8 ± 3.76%) compared to hypoxia-exposed sham-operated controls, reflecting a more severe PH phenotype. These novel models, which exhibit haemodynamic alterations akin to the established hypoxia with SU5416-induced PH model as per published data, could offer a substantial contribution to future PH research and therapeutic development.

High-altitude exercise affects cardiac function. This study investigated how altitude and exercise intensity interacted to affect cardiac function of Sprague-Dawley rats. Four altitudes (410, 3600, 4600 and 5600 m) and three exercise intensities (non-exercise (N), low-intensity exercise (L) and high-intensity exercise (H)) were tested combinatorically. After 4 weeks of exercise, cardiac function and specific markers of myocardial injury were assessed. With regard to cardiac function, (a) at the same intensity, stroke volume and left ventricular end-diastolic volume were higher in the 3600 m group but lower in the 4600 and 5600 m groups; and (b) the heart rate increased with altitude and intensity. The biochemical results showed that the levels of creatine kinase, myoglobin and cardiac troponin I generally increased with increasing altitude and exercise intensity, significantly for creatine kinase and myoglobin at 4600 and 5600 m. For pathological results, (a) in the non-exercise group, pathological damage was observed only in the 5600 N group; and (b) in the exercised state, varying degrees of injury were noted, except for the 410 and 3600 L groups. There may be a turning point at 3600 m where the injury to the heart increases. Myocardial injury markers exhibited abnormalities before cardiac dysfunction. Detecting these markers is crucial to provide warnings for the individual from cardiac disease during high-altitude exercise.

Heart failure (HF) remains a significant global health concern with limited effective treatments available. C1q/TNF-related protein 6 (CTRP6) is a member of the CTRP family analogous to adiponectin and its role in HF pathogenesis remains unclear. Here, we investigated the impact of CTRP6 on HF progression. To mimic heart failure with reduced ejection fraction (HFrEF), we used isoproterenol injection in mice and administered adenovirus vectors expressing CTRP6 (Ad-CTRP6) via tail vein injection. We assessed cardiac function through echocardiography and histology. CTRP6's effects on hypertrophy, fibrosis, apoptosis, oxidative stress and mitochondrial function were analysed. Downstream pathways (phosphorylated AMP-activated protein kinase (p-AMPK), sirtuin 1 (SIRT1) and peroxisome proliferator-activated receptor γ coactivator 1-α (PGC-1α) were studied in heart tissues. In vitro, isoproterenol-stimulated H9c2 cardiomyocytes were treated with CTRP6 to examine viability, apoptosis, F-actin and signalling proteins. Compound C was used to assess AMPK involvement. CTRP6 expression was lower in the plasma of HF patients. In an isoproterenol-induced HFrEF mouse model, adenovirus-mediated overexpression of CTRP6 ameliorated cardiac dysfunction and reduced cardiomyocyte apoptosis, oxidative stress, inflammation and myocardial injury markers. Mechanistically, CTRP6 activation of the AMPK/SIRT1/PGC-1α signalling pathway restored mitochondrial homeostasis, evidenced by reduced mitochondrial reactive oxygen species levels, increased ATP content, and enhanced mitochondrial complex I/III activities in cardiac tissues. In vitro studies using isoproterenol-stimulated H9c2 cardiomyocytes corroborated these findings, demonstrating that CTRP6 upregulation attenuated hypertrophy, apoptosis, oxidative stress and mitochondrial dysfunction. Furthermore, these effects were partially reversed by the AMPK inhibitor Compound C, implicating the involvement of the AMPK pathway in CTRP6-mediated cardioprotection. CTRP6 alleviates HF progression through the AMPK/SIRT1/PGC-1α signalling pathway.