Plasma ATP concentration and venous oxygen content in the forearm during dynamic handgrip exercise

Background It has been proposed that adenosine triphosphate (ATP) released from red blood cells (RBCs) may contribute to the tight coupling between blood flow and oxygen demand in contracting skeletal muscle. To determine whether ATP may contribute to the vasodilatory response to exercise in the forearm, we measured arterialised and venous plasma ATP concentration and venous oxygen content in 10 healthy young males at rest, and at 30 and 180 seconds during dynamic handgrip exercise at 45% of maximum voluntary contraction (MVC). Results Venous plasma ATP concentration was elevated above rest after 30 seconds of exercise (P < 0.05), and remained at this higher level 180 seconds into exercise (P < 0.05 versus rest). The increase in ATP was mirrored by a decrease in venous oxygen content. While there was no significant relationship between ATP concentration and venous oxygen content at 30 seconds of exercise, they were moderately and inversely correlated at 180 seconds of exercise (r = -0.651, P = 0.021). Arterial ATP concentration remained unchanged throughout exercise, resulting in an increase in the venous-arterial ATP difference. Conclusions Collectively these results indicate that ATP in the plasma originated from the muscle microcirculation, and are consistent with the notion that deoxygenation of the blood perfusing the muscle acts as a stimulus for ATP release. That ATP concentration was elevated just 30 seconds after the onset of exercise also suggests that ATP may be a contributing factor to the blood flow response in the transition from rest to steady state exercise

The physiological and clinical importance of cardiorespiratory fitness in people with abdominal aortic aneurysm

NEW FINDINGS: What is the topic of this review? This review focuses on the physiological impact of abdominal aortic aneurysm (AAA) on cardiorespiratory fitness and the negative consequences of low fitness on clinical outcomes in AAA. We also discuss the efficacy of exercise training for improving cardiorespiratory fitness in AAA. What advances does it highlight? We demonstrate the negative impact of low fitness on disease progression and clinical outcomes in AAA. We highlight potential mechanistic determinants of low fitness in AAA and present evidence that exercise training can be an effective treatment strategy for improving cardiorespiratory fitness, postoperative mortality and disease progression. ABSTRACT: An abdominal aortic aneurysm (AAA) is an abnormal enlargement of the aorta, below the level of the renal arteries, where the aorta diameter increases by >50%. As an aneurysm increases in size, there is a progressive increase in the risk of rupture, which ranges from 25 to 40% for aneurysms >5.5 cm in diameter. People with AAA are also at a heightened risk of cardiovascular events and associated mortality. Cardiorespiratory fitness is impaired in people with AAA and is associated with poor (postoperative) clinical outcomes, including increased length of hospital stay and postoperative mortality after open surgical or endovascular AAA repair. Although cardiorespiratory fitness is a well‐recognized prognostic marker of cardiovascular health and mortality, it is not assessed routinely, nor is it included in current clinical practice guidelines for the management of people with AAA. In this review, we discuss the physiological impact of AAA on cardiorespiratory fitness, in addition to the consequences of low cardiorespiratory fitness on clinical outcomes in people with AAA. Finally, we summarize current evidence for the effect of exercise training interventions on cardiorespiratory fitness in people with AAA, including the associated improvements in postoperative mortality, AAA growth and cardiovascular risk. Based on this review, we propose that cardiorespiratory fitness should be considered as part of the routine risk assessment and monitoring of people with AAA and that targeting improvements in cardiorespiratory fitness with exercise training might represent a viable adjunct treatment strategy for reducing postoperative mortality and disease progression

Exercise training for intermittent claudication:a narrative review and summary of guidelines for practitioners

Peripheral artery disease (PAD) is caused by atherosclerotic narrowing of the arteries supplying the lower limbs often resulting in intermittent claudication, evident as pain or cramping while walking. Supervised exercise training elicits clinically meaningful benefits in walking ability and quality of life. Walking is the modality of exercise with the strongest evidence and is recommended in several national and international guidelines. Alternate forms of exercise such as upper- or lower-body cycling may be used, if required by certain patients, although there is less evidence for these types of programmes. The evidence for progressive resistance training is growing and patients can also engage in strength-based training alongside a walking programme. For those unable to attend a supervised class (strongest evidence), home-based or ‘self-facilitated’ exercise programmes are known to improve walking distance when compared to simple advice. All exercise programmes, independent of the mode of delivery, should be progressive and individually prescribed where possible, considering disease severity, comorbidities and initial exercise capacity. All patients should aim to accumulate at least 30 min of aerobic activity, at least three times a week, for at least 3 months, ideally in the form of walking exercise to near-maximal claudication pain

Effects of Exercise in Immersive Virtual Environments on Cortical Neural Oscillations and Mental State

Virtual reality environments are increasingly being used to encourage individuals to exercise more regularly, including as part of treatment those with mental health or neurological disorders. The success of virtual environments likely depends on whether a sense of presence can be established, where participants become fully immersed in the virtual environment. Exposure to virtual environments is associated with physiological responses, including cortical activation changes. Whether the addition of a real exercise within a virtual environment alters sense of presence perception, or the accompanying physiological changes, is not known. In a randomized and controlled study design, moderate-intensity Exercise (i.e., self-paced cycling) and No-Exercise (i.e., automatic propulsion) trials were performed within three levels of virtual environment exposure. Each trial was 5 minutes in duration and was followed by posttrial assessments of heart rate, perceived sense of presence, EEG, and mental state. Changes in psychological strain and physical state were generally mirrored by neural activation patterns. Furthermore, these changes indicated that exercise augments the demands of virtual environment exposures and this likely contributed to an enhanced sense of presence

Endotoxin tolerance in abdominal aortic aneurysm macrophages, in vitro: a case–control study

Macrophages are implicated in the pathogenesis of abdominal aortic aneurysm (AAA). This study examined the environmentally conditioned responses of AAA macrophages to inflammatory stimuli. Plasma- and blood-derived monocytes were separated from the whole blood of patients with AAA (30-45 mm diameter; = 33) and sex-matched control participants ( = 44). Increased concentrations of pro-inflammatory and pro-oxidant biomarkers were detected in the plasma of AAA patients, consistent with systemic inflammation and oxidative stress. However, in monocyte-derived macrophages, a suppressed cytokine response was observed in AAA compared to the control following stimulation with lipopolysaccharide (LPS) (tumor necrosis factor alpha (TNF-α) 26.9 ± 3.3 vs. 15.5 ± 3.2 ng/mL, < 0.05; IL-6 3.2 ± 0.6 vs. 1.4 ± 0.3 ng/mL, < 0.01). LPS-stimulated production of 8-isoprostane, a biomarker of oxidative stress, was also markedly lower in AAA compared to control participants. These findings are consistent with developed tolerance in human AAA macrophages. As Toll-like receptor 4 (TLR4) has been implicated in tolerance, macrophages were examined for changes in TLR4 expression and distribution. Although TLR4 mRNA and protein expression were unaltered in AAA, cytosolic internalization of receptors and lipid rafts was found. These findings suggest the inflamed, pro-oxidant AAA microenvironment favors macrophages with an endotoxin-tolerant-like phenotype characterized by a diminished capacity to produce pro-inflammatory mediators that enhance the immune response

The association between contrast-enhanced ultrasound and near-infrared spectroscopy-derived measures of calf muscle microvascular responsiveness in older adults

Background and Aim Contrast-enhanced ultrasound (CEUS) measures of post-occlusion skeletal muscle microvascular responsiveness demonstrate the microvascular dysfunction associated with ageing and age-related disease. However, the accessibility of CEUS is limited by the need for intravenous administration of ultrasound contrast agents and sophisticated imaging analysis. Alternative methods are required for the broader assessment of microvascular dysfunction in research and clinical settings. Therefore, we aimed to evaluate the level of association and agreement between CEUS and near-infrared spectroscopy (NIRS)-derived measures of post-occlusion skeletal muscle microvascular responsiveness in older adults. Methods During supine rest, participants (n=15, 67±11 years) underwent 5 minutes of thigh cuff-occlusion (200 mmHg). Post-occlusion CEUS measures of calf muscle microvascular responsiveness were made, including time to 95% peak acoustic intensity (TTP95 AI) and the rate of rise (slope AI). Simultaneous measures, including time to 95% peak oxygenated haemoglobin (TTP95 O2Hb) and slope O2Hb, were made using continuous-wave NIRS in the same muscle region. Results There were strong correlations between TTP95 measures derived from CEUS and NIRS (r=0.834, p=<0.001) and the corresponding measures of slope (r=0.735, p=0.004). The limits of agreement demonstrated by Bland Altman plot analyses for CEUS and NIRS-derived measures of TTP95 (-9.67–1.98 s) and slope (-1.29–5.23%. s-1) were smaller than the minimum differences expected in people with microvascular dysfunction. Conclusions The strong correlations and level of agreement in the present study support the use of NIRS as a non-invasive, portable and cost-effective method for assessing post-occlusion skeletal muscle microvascular responsiveness in older adults

The gravitational-wave background null hypothesis: Characterizing noise in millisecond pulsar arrival times with the Parkes Pulsar Timing Array

The noise in millisecond pulsar (MSP) timing data can include contributions from observing instruments, the interstellar medium, the solar wind, solar system ephemeris errors, and the pulsars themselves. The noise environment must be accurately characterized in order to form the null hypothesis from which signal models can be compared, including the signature induced by nanohertz-frequency gravitational waves (GWs). Here we describe the noise models developed for each of the MSPs in the Parkes Pulsar Timing Array (PPTA) third data release, which have been used as the basis of a search for the isotropic stochastic GW background. We model pulsar spin noise, dispersion measure variations, scattering variations, events in the pulsar magnetospheres, solar wind variability, and instrumental effects. We also search for new timing model parameters and detected Shapiro delays in PSR~J0614$-$3329 and PSR~J1902$-$5105. The noise and timing models are validated by testing the normalized and whitened timing residuals for Gaussianity and residual correlations with time. We demonstrate that the choice of noise models significantly affects the inferred properties of a common-spectrum process. Using our detailed models, the recovered common-spectrum noise in the PPTA is consistent with a power law with a spectral index of $\gamma=13/3$, the value predicted for a stochastic GW background from a population of supermassive black hole binaries driven solely by GW emission.Comment: 18 pages, 10 figures. Accepted for publication in ApJ

Compressed representation of a partially defined integer function over multiple arguments

In OLAP (OnLine Analitical Processing) data are analysed in an n-dimensional cube. The cube may be represented as a partially defined function over n arguments. Considering that often the function is not defined everywhere, we ask: is there a known way of representing the function or the points in which it is defined, in a more compact manner than the trivial one

Search for an isotropic gravitational-wave background with the Parkes Pulsar Timing Array

Pulsar timing arrays aim to detect nanohertz-frequency gravitational waves (GWs). A background of GWs modulates pulsar arrival times and manifests as a stochastic process, common to all pulsars, with a signature spatial correlation. Here we describe a search for an isotropic stochastic gravitational-wave background (GWB) using observations of 30 millisecond pulsars from the third data release of the Parkes Pulsar Timing Array (PPTA), which spans 18 years. Using current Bayesian inference techniques we recover and characterize a common-spectrum noise process. Represented as a strain spectrum $h_c = A(f/1 {\rm yr}^{-1})^{\alpha}$, we measure $A=3.1^{+1.3}_{-0.9} \times 10^{-15}$ and $\alpha=-0.45 \pm 0.20$ respectively (median and 68% credible interval). For a spectral index of $\alpha=-2/3$, corresponding to an isotropic background of GWs radiated by inspiraling supermassive black hole binaries, we recover an amplitude of $A=2.04^{+0.25}_{-0.22} \times 10^{-15}$. However, we demonstrate that the apparent signal strength is time-dependent, as the first half of our data set can be used to place an upper limit on $A$ that is in tension with the inferred common-spectrum amplitude using the complete data set. We search for spatial correlations in the observations by hierarchically analyzing individual pulsar pairs, which also allows for significance validation through randomizing pulsar positions on the sky. For a process with $\alpha=-2/3$, we measure spatial correlations consistent with a GWB, with an estimated false-alarm probability of $p \lesssim 0.02$ (approx. $2\sigma$). The long timing baselines of the PPTA and the access to southern pulsars will continue to play an important role in the International Pulsar Timing Array.Comment: 19 pages, 10 figures, Accepted for publication in ApJ