Exercise, inflammation and vascular function in aging and obesity.

Background. While aging is a non-modifiable process, obesity is a reversible condition. However, both are characterized by a low-grade inflammatory profile and vascular dysfunction. Exercise is a non-pharmacological strategy able to counteract the negative effect of aging as well as of obesity. Nonetheless, its short-term and long-term effect on inflammation and vascular function in obese and non-obese elderly individuals are still matter of debate. Still not clear are the differences in the acute inflammatory and vascular response to different types and intensities of exercise in sedentary subjects. Aims. The primary aim was to examine how the inflammatory profile and vascular function in non-obese and obese elderly individuals is affected. A secondary aim was to understand the acute inflammatory and vascular response to different exercise types (i.e. aerobic, A; resistance, R) and intensity (i.e. high, H; low, L) in sedentary obese individuals (OB) compared with normal weight (NW) subjects. Methods. Seventy individuals who attended a structured exercise program (30/40f/m; 75\ub15 years; 5\ub12 years of regular training) were enrolled in study 1 and tested for vascular function (flow-mediated dilation; FMD) and inflammatory profile (plasma CRP, IL-1\u3b2, IL-1ra, IL-6, IL-8, IL-10, TNF-\uf061, MCP-1). Subjects were stratified for age and BMI. Correlations between age, BMI and the measured variables were investigated. In study 2, still ongoing, 5 NW (54\ub17 years; 24.2\ub10.7 BMI) and 5 OB (53\ub16years; 33.7\ub11.2 BMI) subjects were included and tested for FMD and inflammatory profile before and after 4 different exercise sessions. Results. In study 1 inverse correlations were found between age and IL- \u3b2 (r -0.232; p<.05); IL-1ra (r -0.181; p<.05); IL-6 (r -0.255; p<.05); and IL-8 (r -0.248; p<.05). Direct correlations were found between BMI and CRP (r 0.155; p<.05), MCP-1 (r 0.217; p<.05); and TNF-\uf061 (r 0.184; p<.05). An inverse correlation was also found between BMI and FMD (r -0.433; p<.01). In a preliminary analysis of data of study 2, different types and intensities of exercise seem to elicite different acute inflammatory responses in NW and OB. However, most differences did not reach statistical significance. FMD showed a significant increase in the post exercise period for all the 4 exercise sessions in both groups (p<.05) with smaller increases in OB as compared with NW. No significant differences between exercise sessions were found. Conclusion. Sustained, regular exercise can counteract the deleterious effects of aging but not of obesity on vascular function and inflammatory profile. Preliminary results of study 2 lead us to speculate that exercise, both aerobic and resistance exercise as well as both high and low intensity, do not seem to affect adversely the inflammatory profile and the acute vascular response in either obese or non-obese individuals. However, further research is needed to confirm these findings

Aging increases metabolic capacity and reduces work efficiency during handgrip exercise in males

Maximal oxygen uptake and exercise performance typically decline with age. However, there are indications of preserved vascular function and blood flow regulation during arm exercise. Yet, it is unknown if this potential physiological preservation with age is mirrored in peripheral metabolic capacity and V̇O2/watt ratio. Thus, to investigate the effects of aging in the arms, we measured metabolic and vascular responses to 6-minute bouts of dynamic handgrip exercise at 40% and 80% of maximal work rate (WRmax) in eleven young (26±2yr) and twelve old (80±6yr) males, applying Doppler-ultrasound combined with blood samples from a deep forearm vein. At baseline, old had a larger arterial diameter compared to young (p&lt;0.001). During exercise, the two groups reached the same WRmax. V̇O2, blood flow, and oxygen supply were higher (40%WRmax; 80%WRmax, all p&lt;0.01), and arterio-venous oxygen-difference lower (80%WRmax, p&lt;0.02), in old compared to young. Old also had a higher oxygen-excess at 80%WRmax (p&lt;0.01) than young, while no difference in muscle diffusion or oxygen-extraction was detected. Only young exhibited an increase in intensity-induced arterial dilation (p&lt;0.05), and they had a lower mean arterial pressure than old at 80%WRmax (p&lt;0.001). V̇O2/watt (40%WRmax; 80%WRmax) was reduced in old compared to young (both p&lt;0.05). In conclusion, in old and young males with a similar handgrip WRmax, old had a higher V̇O2 during 80%WRmax intensity, achieved by an increased blood flow. This may be a result of the available cardiac output reserve, compensating for reduced work efficiency and attenuated vascular response observed in old

Heart rate-index estimates oxygen uptake, energy expenditure and aerobic fitness in rugby players

The purpose of the study was to verify the suitability of heart rate-index (HRindex) in predicting submaximal oxygen consumption (VO2), energy expenditure (EE) and maximal oxygen consumption (VO2max) during treadmill running in rugby players. Fifteen professional rugby players (99.8 +/- 12.7 kg, 1.85 +/- 0.09 m) performed a miming incremental test while VO2 (breath-bybreath) and heart rate (FIR) were measured. HRindex was calculated (actual HR/resting HR) to predict submaximal and maximal VO2 ({[(HRindex x 6)-5.0] x (3.5 body weight)}) and EE. Measured and predicted VO2 and EE were compared by two-way RM-ANOVA (method, speed), correlation and Bland-Altman analysis. Measured and predicted VO2max were compared by paired t-test, correlation and Bland-Altman analysis. Submaximal VO2 and EE significantly increased (baseline VO2: 8.1 +/- 1.6 ml.kg(-1).min(-1) VO2max: 46.8 +/- 4.3 ml.kg(-1).min(-1), baseline EE: 0.03 +/- 0.01 kcal.kg(-1).min(-1), peak EE: 0.23 +/- 0.03 kcal.kg(-1).min(-1)) as a function of speed (p < 0.001 and p < 0.001 for VO2 and EE respectively) yet measured and predicted values at equal treadmill speeds were not significantly different (p = 0.17; p = 0.16) and highly correlated (r = 0.95; r = 0.94). The Bland-Altman analysis confirmed a non-significant bias between measured and estimated VO2 (measured: 40.3 +/- 10.7, estimated: 40.7 +/- 10.1 ml.kg(-1).min(-1), bias = 1.35 ml.kg(-1).min(-1), z = 1.12, precision = 3.39 ml.kg(-1).min(-1)) and EE (measured: 20.0 +/- 0.05 kcal.kg(-1).min(-1), estimated: 20.0 +/- 0.05 kcal.kg(-1).min(-1), bias = 0.00 kcal.kg(-1).min(-1), z = 0.04, precision = 0.02 kcal.kg(-1).min(-1)). Estimated and predicted VO2max were not statistically different (p = 0.91), highly correlated (r = 0.96), and showed a nonsignificant bias (bias = 0.17, z = 0.22, precision = 1.29 ml.kg(-1).min(-1)). HRindex is a valid field method to track VO2, EE and VO2max during miming in rugby players

Heart rate-index estimates oxygen uptake, energy expenditure and aerobic fitness in rugby players

The purpose of the study was to verify the suitability of heart rate-index (HRindex) in predicting submaximal oxygen consumption (VO2), energy expenditure (EE) and maximal oxygen consumption (VO2max) during treadmill running in rugby players. Fifteen professional rugby players (99.8 \ub1 12.7 kg, 1.85 \ub1 0.09 m) performed a running incremental test while VO2 (breath-by-breath) and heart rate (HR) were measured. HRindex was calculated (actual HR/resting HR) to predict submaximal and maximal VO2 ([(HRindex x 6)-5.0] x (3.5 body weight)) and EE. Measured and predicted VO2 and EE were compared by two-way RM-ANOVA (method, speed), correlation and Bland-Altman analysis. Measured and predicted VO2max were compared by paired t-test, correlation and Bland-Altman analysis. Submaximal VO2 and EE significantly increased (baseline VO2: 8.1 \ub1 1.6 ml\ub7kg-1\ub7min-1VO2max: 46.8 \ub1 4.3 ml\ub7kg-1\ub7min-1, baseline EE: 0.03 \ub1 0.01 kcal\ub7kg-1\ub7min-1, peak EE: 0.23 \ub1 0.03 kcal\ub7kg-1\ub7min-1) as a function of speed (p &lt; 0.001 and p &lt; 0.001 for VO2 and EE respectively) yet measured and predicted values at equal treadmill speeds were not significantly different (p = 0.17; p = 0.16) and highly correlated (r = 0.95; r = 0.94). The Bland-Altman analysis confirmed a non-significant bias between measured and estimated VO2 (measured: 40.3 \ub1 10.7, estimated: 40.7 \ub1 10.1 ml\ub7kg-1\ub7min-1, bias = 1.35 ml\ub7kg-1\ub7min-1, z = 1.12, precision = 3.39 ml\ub7kg-1\ub7min-1) and EE (measured: 20.0 \ub1 0.05 kcal\ub7kg-1\ub7min-1, estimated: 20.0 \ub1 0.05 kcal\ub7kg-1\ub7min-1, bias = 0.00 kcal\ub7kg-1\ub7min-1, z = 0.04, precision = 0.02 kcal\ub7kg-1\ub7min-1). Estimated and predicted VO2max were not statistically different (p = 0.91), highly correlated (r = 0.96), and showed a non-significant bias (bias = 0.17, z = 0.22, precision = 1.29 ml\ub7kg-1\ub7min-1). HRindex is a valid field method to track VO2, EE and VO2max during running in rugby players

The eccentric phase in unilateral resistance training enhances and preserves the contralateral knee extensors strength gains after detraining in women: a randomized controlled trial

The current randomized controlled study investigated whether or not the inclusion of the eccentric phase in resistance training favors the contralateral strength gains after different unilateral protocols, and whether such gains are retained after detraining. Sixty healthy women were randomly assigned to a unilateral concentric-only (CONC), eccentric-only (ECC), concentric-eccentric (TRAD) volume-equated knee extension training or control group (CON). The participants trained 2 days/week for 8 weeks and then did not train for further 8 weeks. Knee extensors isokinetic concentric, eccentric, and isometric peak torque and vastus lateralis muscle thickness were assessed in the contralateral limb at baseline, post-training, and post-detraining. At post-training, concentric peak torque increased in CONC [+9.2%, 95%CI (+6.2/+12.3), p &lt; 0.001, ES: 0.70, 95%CI (0.01/1.39)], ECC [+11.0% (+7.7/+14.2), p &lt; 0.001: ES: 0.66(0.09/1.23)] and TRAD [+8.5%(+5.7/+11.6), p &lt; 0.001, ES: 0.50(0.02/0.98)]. Eccentric peak torque increased in ECC in ECC [+15.0%(+11.4/+20.7), p &lt; 0.001, ES: 0.91(0.14/1.63)] and TRAD [+5.5%(+0.3/10.7), p = 0.013, ES: 0.50(0.05/0.95)]. Isometric peak torque increased in ECC [+11.3(+5.8/16.8), p &lt; 0.001, ES: 0.52(0.10/0.94)] and TRAD [+8.6%(+3.4/+13.7), p &lt; 0.001, ES: 0.55(0.14/0.96)]. No change in eccentric and isometric peak torque occurred in CONC (p &gt; 0.05). Muscle thickness did not change in any group (p &gt; 0.05). At post-detraining, all groups preserved the contralateral strength gains observed at post-training (p &lt; 0.05). The findings showed that ECC and TRAD increased contralateral knee extensors strength in concentric, eccentric, and isometric modality, while CONC only increased concentric strength. The eccentric phase appears to amplify the cross-education effect, permitting a transfer in strength gaining toward multiple testing modalities. Both eccentric-based and traditional eccentric-concentric resistance protocols are recommended to increase the contralateral retention in strength gains after a detraining period

Non-Aβ-dependent factors associated with global cognitive and physical function in alzheimer's disease: a pilot multivariate analysis

Recent literature highlights the importance of identifying factors associated with mild cognitive impairment (MCI) and Alzheimer's Disease (AD). Actual validated biomarkers include neuroimaging and cerebrospinal fluid assessments; however, we investigated non-Aβ-dependent factors associated with dementia in 12 MCI and 30 AD patients. Patients were assessed for global cognitive function (Mini-Mental state examination-MMSE), physical function (Physical Performance Test-PPT), exercise capacity (6-min walking test-6MWT), maximal oxygen uptake (VO₂max), brain volume, vascular function (flow-mediated dilation-FMD), inflammatory status (tumor necrosis factor-α ,TNF- α, interleukin-6, -10 and -15) and neurotrophin receptors (p75NTR and Tropomyosin receptor kinase A -TrkA). Baseline multifactorial information was submitted to two separate backward stepwise regression analyses to identify the variables associated with cognitive and physical decline in demented patients. A multivariate regression was then applied to verify the stepwise regression. The results indicated that the combination of 6MWT and VO₂max was associated with both global cognitive and physical function (MMSE = 11.384 + (0.00599 × 6MWT) - (0.235 × VO₂max)); (PPT = 1.848 + (0.0264 × 6MWT) + (19.693 × VO₂max)). These results may offer important information that might help to identify specific targets for therapeutic strategies (NIH Clinical trial identification number NCT03034746)

Altered vascular endothelium-dependent responsiveness in frail elderly patients recovering from {COVID}-19 pneumonia: preliminary evidence

We evaluated vascular dysfunction with the single passive leg movement test (sPLM) in 22 frail elderly patients at 84 + 31 days after hospitalization for COVID-19 pneumonia, compared to 22 age-, sex- and comorbidity-matched controls (CTRL). At rest, all COVID-19 patients were in stable clinical condition without severe comorbidities. Patients (aged 72 ± 6 years, 73% male) had moderate disability (Barthel index score 77 ± 26), hypoxemia and normocapnia at arterial blood gas analysis and mild pulmonary restriction at spirometry. Values of circulating markers of inflammation (C-reactive protein: CRP; erythrocyte sedimentation rate: ESR) and coagulation (D-dimer) were: 27.13 ± 37.52 mg/dL, 64.24 ± 32.37 mm/1 h and 1043 ± 729 ng/mL, respectively. At rest, femoral artery diameter was similar in COVID-19 and CTRL (p = 0.16). On the contrary, COVID-19 infection deeply impacted blood velocity (p = 0.001) and femoral blood flow (p &lt; 0.0001). After sPLM, peak femoral blood flow was dramatically reduced in COVID-19 compared to CTRL (p = 0.001), as was blood flow ∆peak (p = 0.05) and the area under the curve (p &lt; 0.0001). This altered vascular responsiveness could be one of the unknown components of long COVID-19 syndrome leading to fatigue, changes in muscle metabolism and fibers’ composition, exercise intolerance and increased cardiovascular risk. Impact of specific treatments, such as exercise training, dietary supplements or drugs, should be evaluated

Concurrent metaboreflex activation increases chronotropic and ventilatory responses to passive leg movement without sex-related differences

Previous studies in animal models showed that exercise-induced metabolites accumulation may sensitize the mechanoreflex-induced response. The aim of this study was to assess whether the magnitude of the central hemodynamic and ventilatory adjustments evoked by isolated stimulation of the mechanoreceptors in humans are influenced by the prior accumulation of metabolic byproducts in the muscle. 10 males and 10 females performed two exercise bouts consisting of 5-min of intermittent isometric knee-extensions performed 10% above the previously determined critical force. Post-exercise, the subjects recovered for 5&nbsp;min either with a suprasystolic circulatory occlusion applied to the exercised quadriceps (PECO) or under freely-perfused conditions (CON). Afterwards, 1-min of continuous passive leg movement was performed. Central hemodynamics, pulmonary data, and electromyography from exercising/passively-moved leg were recorded throughout the trial. Root mean square of successive differences (RMSSD, index of vagal tone) was also calculated. Δpeak responses of heart rate (ΔHR) and ventilation ([Formula: see text]) to passive leg movement were higher in PECO compared to CON (ΔHR: 6 ± 5 vs 2 ± 4&nbsp;bpm, p = 0.01; 3.9 ± 3.4 vs 1.9 ± 1.7&nbsp;L&nbsp;min-1, p = 0.02). Δpeak of mean arterial pressure (ΔMAP) was significantly different between conditions (5 ± 3 vs  - 3 ± 3&nbsp;mmHg, p &lt; 0.01). Changes in RMSSD with passive leg movement were different between PECO and CON (p &lt; 0.01), with a decrease only in the former (39 ± 18 to 32 ± 15&nbsp;ms, p = 0.04). No difference was found in all the other measured variables between conditions (p &gt; 0.05). These findings suggest that mechanoreflex-mediated increases in HR and [Formula: see text] are sensitized by metabolites accumulation. These responses were not influenced by biological sex

The role of muscle mass in vascular remodeling: insights from a single-leg amputee model

Purpose Both muscle mass and physical activity are independent mechanisms that play a role in vascular remodeling, however, the direct impact of muscle mass on the structure and function of the vessels is not clear. The aim of the study was to determine the impact of muscle mass alteration on lower limbs arterial diameter, blood flow, shear rate and arterial stiffness. Methods Nine (33 ± 13"yrs) male individuals with a single-leg amputation were recruited. Vascular size (femoral artery diameter), hemodynamics (femoral artery blood flow and shear rate were measured at the level of the common femoral artery in both amputated (AL) and whole limbs (WL). Muscle mass of both limbs, including thigh for AL and thigh and leg for WL, was measured with a DXA system. Results AL muscle mass was reduced compared to the WL (3.2 ± 1.2"kg vs. 9.4 ± 2.1"kg; p = 0.001). Diameter of the femoral artery was reduced in the AL (0.5 ± 0.1"cm) in comparison to the WL (0.9 ± 0.2"cm, p = 0.001). However, femoral artery blood flow normalized for the muscle mass (AL = 81.5 ± 78.7ml" min−1" kg−1,WL = 32.4 ± 18.3; p = 0.11), and blood shear rate (AL = 709.9 ± 371.4" s−1, WL = 526,9 ± 295,6; p = 0.374) were non different between limbs. A correlation was found only between muscle mass and femoral artery diameter (p = 0.003, R = 0.6561). Conclusion The results of this study revealed that the massive muscle mass reduction caused by a leg amputation, but independent from the level of physical activity, is coupled by a dramatic arterial diameter decrease. Interestingly, hemodynamics and arterial stiffness do not seem to be impacted by these structural changes

Brain structural and functional alterations in multiple sclerosis-related fatigue: a systematic review

Fatigue is one of the most disabling symptoms of multiple sclerosis (MS); it influences patients' quality of life. The etiology of fatigue is complex, and its pathogenesis is still unclear and debated. The objective of this review was to describe potential brain structural and functional dysfunctions underlying fatigue symptoms in patients with MS. To reach this purpose, a systematic review was conducted of published studies comparing functional brain activation and structural brain in MS patients with and without fatigue. Electronic databases were searched until 24 February 2021. The structural and functional outcomes were extracted from eligible studies and tabulated. Fifty studies were included: 32 reported structural brain differences between patients with and without fatigue; 14 studies described functional alterations in patients with fatigue compared to patients without it; and four studies showed structural and functional brain alterations in patients. The results revealed structural and functional abnormalities that could correlate to the symptom of fatigue in patients with MS. Several studies reported the differences between patients with fatigue and patients without fatigue in terms of conventional magnetic resonance imaging (MRI) outcomes and brain atrophy, specifically in the thalamus. Functional studies showed abnormal activation in the thalamus and in some regions of the sensorimotor network in patients with fatigue compared to patients without it. Patients with fatigue present more structural and functional alterations compared to patients without fatigue. Specifically, abnormal activation and atrophy of the thalamus and some regions of the sensorimotor network seem linked to fatigue