Contrast-enhanced ultrasound (CEUS) is increasingly used in assessments of skeletal muscle microvascular blood flow responsiveness. In response to limb cuff-occlusion, some studies have reported significant impairments in CEUS measurements of microvascular blood flow in older adults with cardiovascular or metabolic disease, whereas others have failed to detect significant between-group differences, which has brought the reliability of the technique into question. In the absence of a standardized CEUS protocol, there is variance in the duration of cuff-occlusion used, which is likely to influence post-occlusion measurements of muscle microvascular blood flow. We aimed to determine the effect of cuff-occlusion duration by comparing the magnitude and reliability of CEUS measurements of calf muscle microvascular blood flow responsiveness in older adults (n = 15, 67 ± 11 years) following 1, 3 and 5 min occlusion periods. Microvascular blood flow (= microvascular volume × microvascular velocity) within the calf muscle was measured using real-time destruction-replenishment CEUS. Measurements were made following thigh cuff-occlusion (200 mmHg) periods of 1, 3 and 5 min in a random order. Microvascular blood flow was higher following 3 min (3.71 ± 1.46 aU s −1) and 5 min (3.47 ± 1.48 aU s −1) compared with 1 min (2.42 ± 1.27 aU s −1 , P = 0.002), which corresponded with higher microvascular volumes after 3 and 5 min compared with 1 min. Reliability was good following 5 min (intraclass correlation coefficient (ICC) 0.49) compared with poor following 1 min (ICC 0.34) and 3 min (ICC 0.35). This study demonstrates that the magnitude and reliability of calf muscle microvascular responsiveness is enhanced using a 5 min cuff-occlusion protocol compared with 1 min in older adults.

Background and AimContrast-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. MethodsDuring supine rest, participants (n=15, 67611 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 (TTP 95 AI) and the rate of rise (slope AI). Simultaneous measures, including time to 95% peak oxygenated haemoglobin (TTP 95 O 2 Hb) and slope O 2 Hb, were made using continuous-wave NIRS in the same muscle region. ResultsThere were strong correlations between TTP 95 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 TTP 95 (-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. ConclusionsThe strong correlations and level of agreement in the present study support the use of NIRS as a noninvasive, portable and cost-effective method for assessing post-occlusion skeletal muscle microvascular responsiveness in older adults.

Peritoneal macrophages from colchicine-treated mice formed fewer foam cells when incubated with oxidised-LDL. In vitro, addition of 10nM colchicine inhibited foam cell formation from murine bone marrow-derived macrophages, accompanied by reduced glycosylation and surface expression of the oxidised-LDL uptake receptor, CD36. It also decreased uptake of cholesterol crystals by macrophages and inhibited priming and activation of the NLRP3 inflammasome, with reduced secretion of IL-1b and IL-18. Colchicine's anti-atherosclerotic actions were accentuated in a mouse model of unstable plaque, induced by carotid artery tandem stenosis surgery, where it decreased lesion size by 48% (p=0.007), reduced lipid and necrotic core area (p=0.004) and increased collagen content and cap-to-necrotic core ratio (p=0.01), consistent with plaque stabilisation. Conclusion: Colchicine exerts anti-atherosclerotic and plaque-stabilising effects, with inhibition of macrophage-tofoam cell transformation and cholesterol crystal-induced activation of NLRP3.

Background: There is evidence that high-fibre diets have significant health benefits, although the effect of increasing fibre on individuals’ appetite, satiety, and gastrointestinal comfort is not well established, nor is its acceptability and feasibility. Methods: This mixed-methods feasibility randomised control trial included 38 participants allocated to one of three conditions: FibreMAX (two daily servings of 25 g of BARLEYmax®), FibreGRAD (two daily servings with the amount of fibre gradually increased), and Control (two daily servings totalling 25 g of placebo product). Participants completed a food diary at baseline. The Hunger and Fullness Questionnaire and questions regarding gastrointestinal response were completed at baseline and at the end of each week. Participants completed the acceptability of intervention measure and engaged in a semi-structured interview, following trial completion. Results: The qualitative data suggested that increased fibre influenced appetite and fullness perceptions. Baseline fibre consumption and the method of increased fibre increase did not influence our findings. The qualitative results also indicated that the fibre intake was perceived as beneficial to well-being; it influenced feelings of hunger and caused some minor acute gastrointestinal symptoms that dissipated after a short adaption period. Conclusion: This study suggests that increasing fibre intake through BARLEYmax® is a safe intervention that is acceptable to participants.

Purpose: Leg muscle microvascular blood flow (perfusion) is impaired in response to maximal exercise in patients with peripheral artery disease (PAD); however, during submaximal exercise, microvascular perfusion is maintained due to a greater increase in microvascular blood volume compared with that seen in healthy adults. It is unclear whether this submaximal exercise response reflects a microvascular impairment, or whether it is a compensatory response for the limited conduit artery flow in PAD. Therefore, to clarify the role of conduit artery blood flow, we compared whole-limb blood flow and skeletal muscle microvascular perfusion responses with exercise in patients with PAD (n=9; 60±7 years) prior to, and following, lower-limb endovascular revascularization. Materials and Methods: Microvascular perfusion (microvascular volume × flow velocity) of the medial gastrocnemius muscle was measured before and immediately after a 5 minute bout of submaximal intermittent isometric plantar-flexion exercise using contrast-enhanced ultrasound imaging. Exercise contraction-by-contraction whole-leg blood flow and vascular conductance were measured using strain-gauge plethysmography. Results: With revascularization there was a significant increase in whole-leg blood flow and conductance during exercise (p<0.05). Exercise-induced muscle microvascular perfusion response did not change with revascularization (pre-revascularization: 3.19±2.32; post-revascularization: 3.89±1.67 aU.s−1; p=0.38). However, the parameters that determine microvascular perfusion changed, with a reduction in the microvascular volume response to exercise (pre-revascularization: 6.76±3.56; post-revascularization: 2.42±0.69 aU; p<0.01) and an increase in microvascular flow velocity (pre-revascularization: 0.25±0.13; post-revascularization: 0.59±0.25 s−1; p=0.02). Conclusion: These findings suggest that patients with PAD compensate for the conduit artery blood flow impairment with an increase in microvascular blood volume to maintain muscle perfusion during submaximal exercise. Clinical Impact The findings from this study support the notion that the impairment in conduit artery blood flow in patients with PAD leads to compensatory changes in microvascular blood volume and flow velocity to maintain muscle microvascular perfusion during submaximal leg exercise. Moreover, this study demonstrates that these microvascular changes are reversed and become normalized with successful lower-limb endovascular revascularization.