A Cross-Sectional Study of Adiposity by DXA and the Relationship with Endothelial Function and Low-Grade Inflammation.

INTRODUCTION: To evaluate body composition, especially visceral adipose tissue (VAT), by dual-energy x-ray absorptiometry (DXA) and its relation to endothelial function investigated by venous occlusion plethysmography (VOP) and ultrasensitive C-reactive protein (hsCRP). METHODOLOGY: This is a cross sectional study in adults of both sexes divided into group 1 (BMI, 20-24.9, n=30), group 2 (BMI, 25-29.9, n=22), group 3 (BMI, 30-34.9, n=27) and group 4 (BMI, 35-39.9, n=22). VAT was analyzed, among other parameters of adiposity, by DXA Lunar iDXA, and co-related to endothelial function, anthropometric evaluation, cardiometabolic variables and hsCRP. For statistical analysis, tests of comparison between groups and correlation were performed using the software SPSS version 25. RESULTS: Inverse correlation of TFT (total fat mass), % RFM (regional fat mass), FMI (fat mass index) and VAT were identified with increment of arterial blood flow in VOP, except the decrease of the latter, with increase of BMI, adiposity indexes, especially VAT, between groups. hsCRP values showed a direct correlation with progression of adiposity and VAT, between groups. CONCLUSIONS: VAT progression, by DXA analysis, was associated with a decline in endothelial function and increase of inflammation, demonstrating potential use in early identification of individuals with cardiovascular risk (CVR).

Acute effects of exercise with blood flow restriction on endothelial function in healthy young and older populations: a systematic review / Efeitos agudos do exercício com restrição do fluxo sanguíneo na função endotelial de jovens e idosos saudáveis: uma revisão sistemática

The objective of this review is to identify the acute effects of blood flow restriction (BFR) with vs without exercise on endothelial function in healthy individuals and the changes in endothelial function in young and older adults following different levels of exclusive BFR vs free flow. Systematic searches were performed in the following databases: PubMed, Web of Science, Scopus, and Cochrane Library, from inception to July 17, 2021. The studies included healthy individuals who underwent assessments of endothelial function before and after experimental protocols through endothelium-dependent flow-mediated dilatation. In total, 4890 studies were screened, and 6 studies of moderate-to-high methodological quality (Physiotherapy Evidence Database scores 6 ­ 10) including 82 subjects (aged 24 ­ 68 years) were eligible. Overall, flow-mediated dilatation increased in the non-cuffed arm immediately and 15 minutes after exercise, with no change in the cuffed arm (BFR of 60 ­ 80 mmHg). In protocols without exercise, cuff pressures of 25 ­ 30 mmHg applied for 30 minutes did not promote changes in the endothelial function, while those > 50 mmHg induced a dose-dependent attenuation of flow-mediated dilatation only in young individuals. A moderate level of BFR appears to have no effect on endothelial function after acute exercise. In non-exercise conditions, reductions in flow-mediated dilatation seem to result from increased retrograde shear provoked by cuff pressures ≥ 50 mmHg in young but not in older adults. An exercise-related increase in antegrade shear rate leads to a greater nitric oxide-mediated vasodilator response. However, BFR appears to attenuate this effect in young but not in older individuals. (AU)

O objetivo desta revisão foi identificar os efeitos agudos da restrição do fluxo sanguíneo (RFS) com vs. sem exercício na função endotelial de indivíduos saudáveis, bem como as alterações na função endotelial em jovens e idosos após diferentes níveis de RFS vs. fluxo livre. Pesquisas sistemáticas foram realizadas nas bases United States National Library of Medicine (PubMed), Web of Science, Scopus e Cochrane Library até 17 de julho de 2021. Os estudos incluíram indivíduos saudáveis que avaliaram a função endotelial antes e após protocolos experimentais, por meio da dilatação mediada por fluxo. Foi selecionado o total de 4.890 estudos, e foram elegíveis seis de moderada a alta qualidade metodológica (Physioterapy Evidence Database 6 ­ 10 pontos), incluindo 82 indivíduos (24 ­ 68 anos). No geral, a dilatação mediada por fluxo aumentou no braço sem manguito, imediatamente e 15 minutos após o exercício, sem alteração no braço com manguito (RFS de 60 ­ 80 mmHg). Em protocolos sem exercício, pressões do manguito de 25 ­ 30 mmHg aplicadas por 30 minutos não promoveram alterações na função endotelial, enquanto aquelas > 50 mmHg induziram uma atenuação dose-dependente da dilatação mediada por fluxo em indivíduos jovens. Um nível moderado de RFS parece não ter efeito na função endotelial após uma sessão de exercício. Em condições sem exercício, as reduções na dilatação mediada por fluxo parecem resultar do aumento do cisalhamento retrógrado provocado por pressões do manguito ≥ 50 mmHg em jovens, mas não em idosos. O aumento da taxa de cisalhamento anterógrado relacionada ao exercício leva a maior resposta vasodilatadora mediada pelo óxido nítrico. No entanto, a RFS parece atenuar esse efeito em jovens, mas não em . (AU)

Exercise with blood flow restriction improves muscle strength and mass while preserving the vascular and microvascular function and structure of older adults.

BACKGROUND: Changes in muscle mass, strength, vascular function, oxidative stress, and inflammatory biomarkers were compared in older adults after resistance training (RT) performed with low-intensity without blood flow restriction (RT-CON); low-intensity with BFR (RT-BFR); and high-intensity without BFR (RT-HI). METHODS: Thirty-two untrained individuals (72±7 y) performed a 12-week RT after being randomized into three groups: RT-CON -30% of 1 repetition maximum (RM); RT-BFR -30% of 1RM and mild BFR (50% of arterial occlusion pressure); RT-HI -70% of 1 RM. RESULTS: Improvements in handgrip strength were similar in RT-BFR (17%) and RT-HI (16%) vs. RT-CON (-0.1%), but increases in muscle mass (6% vs. 2% and -1%) and IGF-1 (2% vs. -0.1% and -1.5%) were greater (p < 0.05) in RT-BFR vs. RT-HI and RT-CON. Changes in vascular function, morphology, inflammation, and oxidative stress were similar between groups, except for time to reach maximum red blood cell velocity which showed a greater reduction (p < 0.05) in RT-BFR (-55%) vs. RT-HI (-11%) and RT-CON (-4%). CONCLUSION: RT with low intensity and mild BFR improved muscle strength and mass in older individuals while preserving vascular function. This modality should be considered an adjuvant strategy to improve muscle function in older individuals with poor tolerance to high loads.

Sarcopenia in the elderly versus microcirculation, inflammation status, and oxidative stress: A cross-sectional study.

BACKGROUND: Age-related mechanisms of sarcopenia associated with vascular function have been recently suggested. This study compared and tested associations between muscle mass and strength, microcirculation, inflammatory biomarkers, and oxidative stress in older adults classified as sarcopenic and non-sarcopenic. METHODS: Thirty-three physically inactive individuals (72±7 yrs) were assigned to age-matched sarcopenic (SG) and non-sarcopenic (NSG) groups. Between-group comparisons were performed for appendicular skeletal mass (ASM), handgrip and isokinetic strength, microvascular function and morphology, C-reactive protein, insulin-like growth factor-1, tumor necrosis factor-alpha, interleukin-6 (IL-6), soluble vascular cell adhesion molecule-1, soluble intercellular adhesion molecule-1, endothelin-1, and oxidized low-density lipoprotein. RESULTS: ASM and knee isokinetic strength were lower in SG than NSG (P < 0.05). No difference between groups was found for outcomes of microvascular function and morphology, but log-transformed IL-6 concentration was twice greater in SG vs. NSG (P = 0.02). Correlations between ASM index, handgrip and knee isokinetic strength vs. markers of microcirculatory function, capillary diameters, vascular reactivity, and endothelial injury were found only in SG. CONCLUSION: Decreased ASM index and strength have been associated with microcirculatory profile, indicating that microcirculation impairment may be involved somehow in Sarcopenia development. The inflammation status, particularly elevated IL-6, seems to play an important role in this process.

Oral L-Arginine (5 g/day) for 14 Days Improves Microcirculatory Function in Healthy Young Women and Healthy and Type 2 Diabetes Mellitus Elderly Women.

OBJECTIVE: The aim of this study was to investigate the effect of oral supplementation with L-arginine on serum biochemical profile, blood pressure, microcirculation, and vasoreactivity/endothelial function in young controls, and elderly women with and without type 2 diabetes mellitus (T2DM). METHODS: Healthy young (n = 25), healthy elderly (n = 25), and elderly women with type 2 diabetes mellitus (T2DME, n = 23, glycated Hb ≥6.4% and mean of 7.7 years for duration of the disease), aged 18-30 and older than 65 years, respectively, were included in the study. All patients underwent biochemical analysis (fasting glycemia and lipidogram), arterial blood pressure, nailfold videocapillaroscopy (capillary diameters, functional capillary density [FCD], peak red blood cell velocity [RBCVmax] after 1 min ischemia, time to reach peak RBCV [TRBCVmax]), and venous occlusion plethysmography (vasoreactivity), before and after 14 days of oral supplementation with L-arginine (5 g/day). RESULTS: L-Arginine did not change fasting glycemia and lipidogram, but it decreased systolic, diastolic, and mean arterial pressure in elderly women, increased RBCVmax in all groups, and did not decrease TRBCVmax in T2DME. Capillary diameters and FCD remained unchanged in all groups. L-Arginine improved vasoreactivity during reactive hyperemia and after sublingual nitroglycerin (0.4 mg) in all groups. CONCLUSION: L-Arginine supplementation (5g/day during 14 days) was able to improve vascular/microvascular health in the elderly women with or without T2DM.

Non-invasive techniques to access in vivo the skin microcirculation in patients.

The microcirculation is composed of blood vessels with mean internal diameter smaller than 100 µm. This structure is responsible for survival of cells and in the last 50 years its study has become increasingly interesting because it often participates in the pathophysiology of several diseases or can determine better or worse prognosis for them. Due to the growing importance of knowing more about the microcirculation, several techniques have been developed and now it is possible to study its structure or function. In the last 25 years, the cutaneous microcirculation has emerged as an accessible and representative portion of generalized vascular bed allowing the examination of mechanisms of microcirculatory function and dysfunction. This mini review presents several techniques used for non-invasive access to skin microcirculation, such as Nailfold Videocapillaroscopy, Orthogonal Polarization Spectral Imaging, Sidestream Dark Field Imaging, Incident Dark field Illumination, Laser Doppler Flowmetry, and Laser Speckle Contrast Imaging applied. The techniques presented will describe which types of variables (structural or functional) can be evaluated, their limitations and potential uses.

Muscle mass, strength, bone mineral density and vascular function in middle-aged people living with HIV vs. age-matched and older controls.

INTRODUCTION: Combination antiretroviral therapy (cART) substantially extended the life of people living with HIV (PLHIV). However, prolonged HIV infection and cART increase the risk of comorbidities accelerating age-related muscle, bone, and vascular disorders. This cross-sectional study compared muscle mass and strength, bone mineral density (BMD), and vascular function in middle-aged PLHIV treated with cART vs. non-infected age-matched and older controls. METHODS: After careful screening for secondary diseases and medications, body composition, muscular and vascular function were assessed in 12 PLHIV (43.9±8.7 yrs old; HIV-infection for 16.2±8.6 yrs; on cART for 11.6±9.2 yrs), 12 age-matched (CONT, 43.2±8.5 yrs old), and 12 older (OLDER, 74.4±8.3 yrs old) controls through dual x-ray absorptiometry, isokinetic dynamometry, and venous occlusion plethysmography, respectively. RESULTS: PLHIV and CONT showed similar relative muscle mass (65.3±8.0 vs. 66.9±7.3%, respectively; P= 0.88) and strength (160.7±53.9 vs. 152.0±52.9 N.m-1, respectively; P= 0.90), which were greater than OLDER (80.6±18.8 N.m-1; P= 0.001). Total BMD was similar in PLHIV (1.04±0.13 g.cm-2) and OLDER (1.00±0.15 g.cm-2, P= 0.86), and both groups presented lower values than CONT (1.20±0.13 g.cm-2, P< 0.01). No significant difference across groups was detected for macrovascular reactivity (P= 0.32). CONCLUSION: Age-related osteopenia might be accelerated in middle-aged PLHIV on prolonged cART, as their BMD approached values found in older adults. On the other hand, muscle mass, isokinetic strength, and vasodilation capacity were similar in PLHIV and age-matched uninfected controls.

Peripheral microvascular dysfunction is also present in patients with ischemia and no obstructive coronary artery disease (INOCA).

BACKGROUND: In patients with ischemia and no obstructive coronary artery disease (INOCA), coronary microvascular dysfunction is associated with higher rate of major adverse cardiovascular events. OBJECTIVE: To demonstrate if microvascular dysfunction present in coronary microcirculation of patients with INOCA may be detected noninvasively in their peripheral circulation. METHODS: 25 patients with INOCA and 25 apparently healthy individuals (controls) were subjected to nailfold videocapillaroscopy (NVC) and venous occlusion plethysmography (VOP) to evaluate peripheral microvascular function and blood collection for biomarkers analysis, including soluble vascular cell adhesion molecule-1 (sVCAM-1), endothelin-1 (ET-1) and C-reactive protein (CRP). RESULTS: Red blood cell velocity (RBCV) before and after ischemia (RBCVmax) were significantly lower in patients with INOCA (p = 0.0001). Time to reach maximal red blood cell velocity (TRBCVmax) was significantly longer in INOCA group (p = 0.0004). Concerning VOP, maximal blood flow (p = 0.004) and its relative increment were significantly lower in patients with INOCA (p = 0.0004). RBCVmax showed significant correlations with sVCAM-1 (r = -0.38, p < 0.05), ET-1 (r = -0.73, p < 0.05) and CRP (r = -0.33, p < 0.05). Relative increment of maximal post-ischemic blood flow was significantly correlated with sVCAM-1 (r = -0.42, p < 0.05) and ET-1 (r = -0.48, p < 0.05). CONCLUSIONS: The impairment of microvascular function present in coronary microcirculation of patients with INOCA can be also detected in peripheral microcirculation.

Acute effects of physical exercise with different levels of blood flow restriction on vascular reactivity and biomarkers of muscle hypertrophy, endothelial function and oxidative stress in young and elderly subjects - A randomized controlled protocol.

BACKGROUND: Gains in muscle mass and strength have been documented in exercise training with blood flow restriction (BFR). However, the impact of retrograde blood flow during BFR training on vascular health remains unclear. The present study designed a protocol to evaluate the acute effects of exercise performed with different levels of BFR on vascular reactivity and biomarkers of endothelial function, oxidative stress, and muscle hypertrophy in young and older individuals. METHODS AND STUDY DESIGN: Sixty-eight physically inactive eutrophic men [34 young (18-25-yrs old) and 34 elderly (≥65-yrs old)] will be included in the study. Subjects will undergo three experimental protocols: a) control (ExCON) - handgrip exercise with intensity of 30% of the maximum voluntary contraction (MVC); b) blood flow restriction (ExBFR) - handgrip exercise with a resistance of 30% of the MVC with low level of BFR [80% of arterial occlusion pressure at rest (rAOP)]; and c) arterial occlusion pressure (ExAOP) - handgrip exercise with a resistance of 30% of the MVC with high level of BFR (120% of rAOP). Primary outcomes will be: a) vascular reactivity assessed by venous occlusion plethysmography; b) endothelial function (nitric oxide and apoptotic endothelial micro particles; c) oxidative stress (thiobarbituric acid reactive substances). Growth hormone and lactate concentration will be measured as secondary outcomes reflecting the hypertrophic drive and metabolic stress, respectively. DISCUSSION: The findings of the present study may help to elucidate the age-related impacts of BFR training on the vascular health.

Does Resistance Training with Blood Flow Restriction Affect Blood Pressure and Cardiac Autonomic Modulation in Older Adults?

Resistance training (RT) with blood flow restriction (BFR) appears to accelerate muscle hypertrophy and strength gains in older populations. However, the training-related effects of RT with BFR upon blood pressure (BP) and cardiac autonomic modulation in the elderly remains unclear. The objective of this study is to compare the chronic effects of low-intensity RT performed with soft BFR (BFR) vs. high-intensity (HI) and low-intensity RT (CON) without BFR on BP and heart rate variability (HRV) indices in older adults. Thirty-two physically inactive participants (72 ± 7 yrs) performed RT for upper and lower limbs (50-min sessions, 3 times/week) for 12 weeks, being assigned into three groups: a) BFR; 30% of 1 repetition maximum (RM) with BFR corresponding to 50% of arterial occlusion pressure; b) HI; 70% of 1RM without BFR; c) CON; 30% of 1 RM without BFR. Resting BP and HRV were assessed at rest in the supine position, before and after exercise interventions. Systolic BP (Δ = -7.9 ± 8.0 mmHg; p = 0.002; effect size = 0.62), diastolic BP (Δ = trace length by the duration of the test 5.0 ± 6.0 mmHg; p = 0.007; effect size = 0.67) and mean arterial pressure (Δ = -6.3 ± 6.5 mmHg; p = 0.003/effect size = 0.77) reduced after BFR, remaining unaltered in HI and CON. HRV indices of sympathetic and vagal modulation did not change in all groups (p ≥ 0.07 for all comparisons). 12-wk RT with low intensity and relatively soft BFR substantially reduced BP at rest in older adults vs. traditional RT performed with either low or high intensity. Those reductions were not parallel to changes in autonomic modulation.

Effects of moderate and high intensity isocaloric aerobic training upon microvascular reactivity and myocardial oxidative stress in rats.

Systemic and central cardiovascular adaptations may vary in response to chronic exercise performed with different intensities and volumes. This study compared the effects of aerobic training with different intensities but equivalent volume upon microvascular reactivity in cremaster muscle and myocardial biomarkers of oxidative stress in Wistar rats. After peak oxygen uptake (VO2peak) assessment, rats (n = 24) were assigned into three groups: moderate-intensity exercise training (MI); high-intensity exercise training (HI); sedentary control (SC). Treadmill training occurred during 4 weeks, with exercise bouts matched by the energy expenditure (3.0-3.5 Kcal). Microvascular reactivity was assessed in vivo by intravital microscopy in cremaster muscle arterioles, while biomarkers of oxidative stress and eNOS expression were quantified at left ventricle and at aorta, respectively. Similar increasing vs. sedentary control group (SC) occurred in moderate intensity training group (MI) and high-intensity training group (HI) for endothelium-dependent vasodilation (10-4M: MI: 168.7%, HI: 164.6% vs. SC: 146.6%, P = 0.0004). Superoxide dismutase (SOD) (HI: 0.13 U/mg vs. MI: 0.09 U/mg and SC: 0.06 U/mg; P = 0.02), glutathione peroxidase (GPX) (HI: 0.00038 U/mg vs. MI: 0.00034 U/mg and SC: 0.00024 U/mg; P = 0.04), and carbonyl protein content (HI: 0.04 U/mg vs. MI: 0.03 U/mg and SC: 0.01 U/mg; P = 0.003) increased only in HI. No difference across groups was detected for catalase (CAT) (P = 0.12), Thiobarbituric acid reactive substances (TBARS) (P = 0.38) or eNOS expression in aorta (P = 0.44). In conclusion, higher exercise intensity induced greater improvements in myocardium antioxidant defenses, while gains in microvascular reactivity appeared to rely more on exercise volume than intensity.

Strength training with blood flow restriction - a novel therapeutic approach for older adults with sarcopenia? A case report.

INTRODUCTION: A 91-year-old sedentary man presenting exhaustion, lower-limb weakness, hypertension, and history of multiple falls was diagnosed with sarcopenia - appendicular skeletal muscle mass index (ASM) of 7.10 kg/m2. PURPOSE: To investigate the effects of strength training performed with low intensity in isolation (LI) or with blood flow restriction (LI-BFR) on strength, muscle mass, IGF-1, endothelial function, microcirculation, inflammatory biomarkers, and oxidative stress. METHODS: In the first 3 months, LI was performed with intensity corresponding to 30% of 1 repetition maximum, followed by 1 month of inactivity, and another 3 months of LI-BFR (similar load than LI concomitant to BFR equivalent to 50% of resting systolic blood pressure). RESULTS: LI-BFR, but not LI improved muscle mass, ASM, handgrip strength, isokinetic peak torque, IL-6, and IGF-1. Endothelial function, red blood cell velocity, and concentrations of C-reactive protein, and soluble intercellular adhesion molecules-1 improved after both LI and LI-BFR. Endothelin-1 and oxidative stress increased after LI-BFR, and lowered after LI. CONCLUSION: LI-BFR, but not LI improved strength, muscle mass, IGF-1, endothelial function, and selected inflammatory markers in a nonagenarian sarcopenic patient. These results are promising and suggest that LI-BFR should be considered as an alternative to prevent muscle loss and improve functional fitness in frail older populations.

Increased vascular function and superoxide dismutase activity in physically active vs inactive adults living with HIV.

This study compared macro- and microvascular endothelial function and redox status in active vs inactive HIV-infected patients (HIVP) under antiretroviral therapy. Using a cross-sectional design, macro- and microvascular reactivity, systemic microvascular density, and oxidative stress were compared between 19 HIVP (53.1 ± 6.1 year) enrolled in a multimodal training program (aerobic, strength and flexibility exercises) for at least 12 months (60-minutes sessions performed 3 times/wk with moderate intensity) vs 25 sedentary HIVP (51.2 ± 6.3 year). Forearm blood flow during reactive hyperemia (521.7 ± 241.9 vs 361.4% ± 125.0%; P = 0.04) and systemic microvascular density (120.8 ± 21.1 vs 105.6 ± 25.0 capillaries/mm2 ; P = 0.03) was greater in active than inactive patients. No significant difference between groups was detected for endothelium-dependent and independent skin microvascular vasodilation (P > 0.05). As for redox status, carbonyl groups (P = 0.22), lipid peroxidation (P = 0.86), catalase activity (P = 0.99), and nitric oxide levels (P = 0.72) were similar across groups. However, superoxide dismutase activity was greater in active vs inactive HIVP (0.118 ± 0.013 vs 0.111 ± 0.007 U/mL; P = 0.05). Immune function reflected by total T CD4 and T CD8 counts (cell/mm3 ) did not differ between active and inactive groups (P > 0.82). In conclusion, physically active HIVP exhibited similar immune function, but greater macrovascular reactivity, systemic microvascular density, and superoxide dismutase activity than inactive patients of similar age.

Effects of açaí and cilostazol on skin microcirculation and viability of TRAM flaps in hamsters.

BACKGROUND: Tissue necrosis caused by insufficient perfusion is a major complication in flap transfer. This study evaluated whether treatment with cilostazol or hydroalcoholic extract of seeds of Euterpe oleracea Mart. (açaí) protects the transverse rectus abdominis myocutaneous (TRAM) flap against ischemic damage in hamsters. MATERIALS AND METHODS: Fifty-four hamsters were divided into three oral treatment groups: placebo, açaí, or cilostazol. Caudally based, unipedicled TRAM flaps were raised, sutured back, classified into four vascular zones (I-IV), and evaluated for tissue viability, capillary blood flow (CBF), perfused vessel density (PVD), and microvascular flow index (MFI) by orthogonal polarization spectral imaging at three time points: immediately postoperatively (IPO), 24 h postoperatively (24hPO), and 7 d postoperatively (7POD). RESULTS: Comparing to placebo, açaí increased PVD at IPO and açaí and cilostazol increased CBF and PVD at 24hPO in zone I; cilostazol increased CBF, PVD, and MFI at IPO, and CBF at 24hPO in zone II; açaí and cilostazol increased CBF at all time points and PVD and MFI at IPO and 24hPO in zone III; cilostazol increased CBF at IPO and 7POD, açaí increased CBF at 7POD, and both increased PVD and MFI at all time points in zone IV; and açaí and cilostazol increased the percentage of viable area in zones III and IV. CONCLUSIONS: Açaí and cilostazol treatments had a protective effect against ischemic damage to TRAM flaps in hamsters, improving microvascular blood flow and increasing the survival of flap zones contralateral to the vascular pedicle (zones III and IV).

Microcirculation and biomarkers in patients with resistant or mild-to-moderate hypertension: a cross-sectional study.

Microcirculation influences peripheral vascular resistance and therefore contributes to arterial blood pressure. The aim of this study was to investigate the correlation between serum markers of inflammation and microcirculatory parameters observed by nailfold videocapillaroscopy (NVC) in patients with resistant (RH, 58 [50-63] years, n = 25) or mild-to-moderate hypertension (MMH, 56 [47-64] years, n = 25) compared to normotensive patients (control group (CG), 33 [27-52] years, n = 25). C-reactive protein (CRP), endothelin, adiponectin, I-CAM and V-CAM levels were obtained by laboratory analysis. Functional capillary density (FCD; the number of capillaries with flowing red blood cells by unit tissue area), capillary diameters, maximum red blood cell velocity (RBCVmax) during the reactive hyperemia response/RBCVbaseline after 1 min of arterial occlusion at the finger base and time to reach RBCVmax were determined by NVC. A sub-analysis was also conducted on hypertensive patients not taking statins, with controlled/uncontrolled blood pressure. The RH group showed lower RBCV and RBCVmax values and longer TRBCVmax compared to MMH and CG patients, with worse values in those with uncontrolled blood pressure. FCD and diameters showed no significant differences among the three groups, with higher CRP values in the RH and MMH groups. An increase in endothelin was observed only in patients not taking statins in both hypertensive groups. Patients with severe hypertension and uncontrolled blood pressure levels presented more pronounced microvascular dysfunction, as well as higher serum values for CRP and endothelin (without statin treatment), suggesting that the use of statins decreases endothelin release.

Evaluation of endothelial function by VOP and inflammatory biomarkers in patients with arterial hypertension.

Hypertension is associated with microcirculatory impairment. Our objectives were to evaluate endothelial function and inflammatory biomarkers in patients with resistant (RH) and mild to moderate (MMH) arterial hypertension in comparison to normotensives (control group-CG). Three groups, 25 patients each, have been investigated, by anamnesis, venous occlusion plethysmography (VOP) and serum determination of adhesion molecules (VCAM, ICAM), adiponectin, endothelin and C-reactive protein (CRP). Patients not using statins and with or without blood pressure control were also analyzed. RH group showed smaller percentage increase of maximum forearm blood flow (FBF) (endothelial-dependent vasodilatation) than controls (p < 0.05), but no significant difference could be detected between MMH and CG groups on maximum FBF and minimum vascular resistance post-ischemia. RH and MMH groups showed higher resistance averages compared to controls (p < 0.05). Uncontrolled BP in hypertensive patients showed worse results for blood flow and resistance. Endothelial-independent vasodilatation was not affected. Endothelin levels were higher in RH and MMH groups (p < 0.05) not using statins. CRP was significantly higher only in RH compared to CG (p < 0.05). In conclusion patients with severe hypertension and lack of blood pressure control showed greater impairment of endothelial function with higher CRP and endothelin levels.

Relationship between biomarkers of inflammation, oxidative stress and endothelial/microcirculatory function in successful aging versus healthy youth: a transversal study.

BACKGROUND: There is a functional decline of endothelial- dependent vasodilatation in the aging process. The aims of this study were to investigate if various microcirculatory parameters could correlate to anthropometrical variables, oxidative stress and inflammatory biomarkers in successful aging and compare the results to young healthy controls. METHODS: Healthy elderly women (HE, 74.0 ± 8.7 years, n = 11) and young controls (YC, 23.1 ± 3.6 years, n = 24) were evaluated through nailfold videocapillaroscopy (NVC), venous occlusion plethysmography (VOP) and laboratorial analysis. Functional capillary density (FCD) and diameters, maximum red blood cell velocity (RBCVmax) during the reactive hyperemia response/RBCVbaseline after 1 min arterial occlusion at the finger base, time to reach RBCVmax were determined by NVC, peak increment of forearm blood flow (FBF) during the reactive hyperemia response (%Hyper) and after 0.4 mg sublingual nitroglycerin (%Nitro) by VOP and lipidogram, fibrinogen, fasting and postload glucose, oxidized LDL-cholesterol (oxLDL), sICAM, sVCAM, sE-Selectin, interleukines 1 and 6 and TNF-α by laboratorial analysis. Correlations and linear multiple regression (LMR) between %Hyper, %Nitro, microcirculatory parameters, oxidative stress and inflammatory biomarkers were investigated. RESULTS: sVCAM, sE-Selectin and oxLDL were higher and RBCVmax/RBCVbaseline and %Hyper lower in HE, while %Nitro and FCD remained unchanged. Fibrinogen, LDL-cholesterol, oxLDL correlated negatively to %Hyper while sVCAM correlated negatively to %Hyper and RBCVmax/RBCVbaseline. Healthy aged women presented dilated capillaries with sustained perfusion and endothelial dysfunction with preserved vascular smooth muscle reactivity. Fibrinogen, LDL-cholesterol, oxidized-LDL and sVCAM correlated negatively to endothelial function but not to microcirculatory parameters. Oxidized-LDL and sVCAM could determine %Hyper through LMR. CONCLUSION: Oxidized-LDL and sVCAM might be used as endothelial dysfunction biomarkers for elderly with normal cardiovascular risk factors.

Increment of body mass index is positively correlated with worsening of endothelium-dependent and independent changes in forearm blood flow.

Obesity is associated with the impairment of endothelial function leading to the initiation of the atherosclerotic process. As obesity is a multiple grade disease, we have hypothesized that an increasing impairment of endothelial and vascular smooth muscle cell functions occurs from lean subjects to severe obese ones, creating a window of opportunities for preventive measures. Thus, the present study was carried out to investigate the grade of obesity in which endothelial dysfunction can be detected and if there is an increasing impairment of endothelial and vascular smooth muscle cell functions as body mass index increases. According to body mass index, subjects were allocated into five groups: Lean controls (n = 9); Overweight (n = 11); Obese class I (n = 26); Obese class II (n = 15); Obese class III (n = 19). Endothelial and vascular smooth muscle cell functions were evaluated measuring forearm blood flow responses to increasing intra-arterial infusions of acetylcholine and sodium nitroprusside using venous occlusion plethysmography. We observed that forearm blood flow was progressively impaired from lean controls to severe obese and found no significant differences between Lean controls and Overweight groups. Known determinants of endothelial dysfunction, such as inflammatory response, insulin resistance, and diagnosis of metabolic syndrome, did not correlate with forearm blood flow response to vasodilators. Moreover, several risk factors for atherosclerosis were excluded as independent predictors after confounder-adjusted analysis. Our data suggests that obesity per se could be sufficient to promote impairment of vascular reactivity, that obesity class I is the first grade of obesity in which endothelial dysfunction can be detected, and that body mass index positively correlates with the worsening of endothelium-dependent and independent changes in forearm blood flow.

Preconditioning of the response to ischemia/ reperfusion-induced plasma leakage in hamster cheek pouch microcirculation.

OBJECTIVE: Ischemic preconditioning and some drugs can protect tissues from injury by preserving microcirculation. This study evaluated vascular permeability in a hamster cheek pouch preparation using either short ischemic periods or bradykinin as preconditioning stimuli followed by 30 min of ischemia/reperfusion. METHOD: Sixty-six male hamsters were divided into 11 groups: five combinations of different ischemic frequencies and durations (one, three or five shorts periods of ischemia, separated by one or five minutes) with 10 min intervals between the ischemic periods, followed by 30 min ischemia/reperfusion; three or five 1 min ischemic periods with 10 min intervals between them followed by the topical application of histamine (2 µM); bradykinin (400 nM) followed by 30 min of ischemia/reperfusion; and three control groups (30 min of ischemia/reperfusion or histamine or bradykinin by themselves). Macromolecular permeability was assessed by injection of fluorescein-labeled dextran (FITC-dextran, MW= 150 kDa; 250 mg/Kg body weight), and the number of leaks/cm2 was counted using an intravital microscope and fluorescent light in the cheek pouch. RESULTS: Plasma leakage (number of leaks/cm²) was significantly reduced by preconditioning with three and five 1 min ischemic periods, one and three 5 min ischemic periods and by bradykinin. Histamine-induced macromolecular permeability was also reduced after three periods of 5 min of ischemia. CONCLUSION: Short ischemic periods and bradykinin can function as preconditioning stimuli of the ischemia/reperfusion response in the hamster cheek pouch microcirculation. Short ischemic periods also reduced histamineinduced macromolecular permeability.

Preconditioning of the response to ischemia/ reperfusion-induced plasma leakage in hamster cheek pouch microcirculation

OBJECTIVE: Ischemic preconditioning and some drugs can protect tissues from injury by preserving microcirculation. This study evaluated vascular permeability in a hamster cheek pouch preparation using either short ischemic periods or bradykinin as preconditioning stimuli followed by 30 min of ischemia/reperfusion. METHOD: Sixty-six male hamsters were divided into 11 groups: five combinations of different ischemic frequencies and durations (one, three or five shorts periods of ischemia, separated by one or five minutes) with 10 min intervals between the ischemic periods, followed by 30 min ischemia/reperfusion; three or five 1 min ischemic periods with 10 min intervals between them followed by the topical application of histamine (2 µM); bradykinin (400 nM) followed by 30 min of ischemia/reperfusion; and three control groups (30 min of ischemia/reperfusion or histamine or bradykinin by themselves). Macromolecular permeability was assessed by injection of fluorescein-labeled dextran (FITC-dextran, MW= 150 kDa; 250 mg/Kg body weight), and the number of leaks/cm2 was counted using an intravital microscope and fluorescent light in the cheek pouch. RESULTS: Plasma leakage (number of leaks/cm²) was significantly reduced by preconditioning with three and five 1 min ischemic periods, one and three 5 min ischemic periods and by bradykinin. Histamine-induced macromolecular permeability was also reduced after three periods of 5 min of ischemia. CONCLUSION: Short ischemic periods and bradykinin can function as preconditioning stimuli of the ischemia/reperfusion response in the hamster cheek pouch microcirculation. Short ischemic periods also reduced histamineinduced macromolecular permeability.