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.

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.

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.

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.

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.

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.

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.

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.

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)

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.

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.

Effects of microbubbles and ultrasound on the microcirculation: observation on the hamster cheek pouch.

BACKGROUND: In view of the debate on the safety of using ultrasound associated with microbubbles, we investigated the microvascular effects in situations of potential clinical interest. METHODS: Ultrasound, microbubbles, and their association were evaluated on the cheek pouch microcirculation in 96 male hamsters (n = 6 in each group): control; ischemia-reperfusion, 30 minutes total ischemia followed by reperfusion; hyperinsulinemia and hyperglycemia (substitution of the drinking water by 10% fructose solution for 3 months); and endotoxic shock (induced by Escherichia coli lipopolysaccharide). The heart rate, mean arterial pressure, number of rolling and adhered leukocytes, and arteriolar and venular diameters were analyzed. RESULTS: Heart rate and mean arterial pressure were lower in the endotoxic shock group than in the control group. Ultrasound alone or associated with microbubbles decreased the number of rolling and adhered leukocytes in the ischemia-reperfusion and hyperinsulinemia and hyperglycemia groups and increased venular diameter in the ischemia-reperfusion group. CONCLUSION: The use of ultrasound decreases inflammation. Although it has not been established that pseudo-anaphylaxis can be assessed by intravital microscopy, microbubble administration does not increase venular leukocyte adhesion.

Effects of buflomedil and pentoxifylline on hamster skin-flap microcirculation: prediction of flap viability using orthogonal polarization spectral imaging.

OBJECTIVE: This study investigated the effects of buflomedil and pentoxifylline, both of which are used in reconstructive surgery of hamster skin flap microcirculation, and evaluated the skin flap survival rate by orthogonal polarization spectral imaging. METHOD: Twenty-four adult male Syrian golden hamsters were divided into three groups: a control (C, 0.1 ml 0.9% saline), buflomedil (B, 3 mg/kg/day), and pentoxifylline group (P, 14.5 mg/kg/day). Treatments administered intraperitoneally were initiated 1 hour before skin flap preparation and continued for 7 days post-operatively at 12-hour intervals. Preparations (skin flaps) were divided into 12 fields, which were organized into six bands. Functional capillary density (FCD, in mm/mm(2)), distance from the skin flap base to blood flow cessation (Dist(with flow), in cm), percentage of viable skin (VA, in%), and qualitative analysis of blood flow by orthogonal polarization spectral imaging were performed at 1 and 24 hours and on the seventh post-operative day. RESULT: Bands IV, V, and VI presented no flow independent of time. The functional capillary density group B was higher than that of groups C and P, primarily after 24 hours. All groups showed an increase in D with time but reached similar final distances (C = 2.73, B = 2.78 and P = 2.70 cm). Moreover, the percentage of viable areas remained at approximately 50%. The orthogonal polarization spectral imaging was useful to assess viability by counting fields with and without blood flow. CONCLUSIONS: Functional capillary density values were higher in the buflomedil group compared to the control and pentoxifylline groups in this model. Functional capillary density did not influence D or the percentage of VA, and the technique showed favorable potential to assess/predict the viability of skin flaps within 1 h after surgery.

Metabolic disturbances linked to obesity: the role of impaired tissue perfusion.

Associated with elevated risk of cardiovascular events and cancer, obesity is a worldwide problem affecting developed and developing countries. Microcirculatory vessels, represented by arterioles, capillaries and venules (mean internal diameter < 100 microm), are the place where blood/tissue nutrition and exchange effectively take place. Microvascular dysfunction is an early event in obesity probably secondary to endothelial dysfunction and capillaries rarefaction. New research techniques allow the investigation of the microcirculation in different vascular beds in humans. Studies suggest a link between endothelial dysfunction and visceral obesity. Oxidative stress, inflammation and renin-angiotensin system are among factors considered to be involved on microvascular dysfunction in obesity. Microcirculatory impairment present in obesity suggests that it could be an important causal factor in obesity-related disorders such as insulin resistance and hypertension.

Effects of cilostazol and pentoxifylline on forearm reactive hyperemia response, lipid profile, oxidative stress, and inflammatory markers in patients with intermittent claudication.

Peripheral arterial disease may lead to lower limb claudication and increased risk of systemic vascular dysfunction. In this article, the authors have investigated the peripheral vascular dysfunction evaluating forearm blood flow using venous occlusion plethysmography, lipid profile, and C-reactive protein in 60 patients with moderate intermittent claudication treated during 20 weeks with placebo (n = 16), cilostazol (200 mg/d; n = 17), or pentoxifylline (1200 mg/d; n = 15) in a randomized double-blinded clinical trial, taking into account smoking. Forearm blood flow after reactive hyperemia response (FBF(h) ) or oral nitroglycerine spray to evaluate endothelial-dependent and endothelial-independent vasodilation, respectively, pain-free and maximal walking distance, levels of C-reactive protein, triglycerides, cholesterol, low-density lipoprotein, and high-density lipoprotein-cholesterol in plasma were determined. The results showed that there was an improvement in the high-density lipoprotein-cholesterol, pain-free and maximal walking distance, and FBF(h) independent of treatment in nonsmoking patients. Cilostazol increased high-density lipoprotein-cholesterol level, maximal walking distance, and FBF(h), whereas pentoxifylline reduced C-reactive protein level and increased maximal walking distance in total and nonsmoking groups. No treatment was effective in smokers.

Treatment of essential hypertension does not normalize capillary rarefaction.

OBJECTIVES: To determine if capillary rarefaction persists when hypertension is treated with angiotensin converting enzyme inhibitor, thiazidic diuretic and/or beta-blocker, and to identify which microcirculatory alterations (structural and functional) persist after anti-hypertensive treatment. METHODS: We evaluated 28 well-controlled essential hypertensive patients and 19 normotensive subjects. Nailfold videocapillaroscopy examination of the fourth finger of the left hand was used to determine the functional capillary densities at baseline, during post-occlusive hyperemia, and after venous congestion. Capillary loop diameters (afferent, apical and efferent) and red blood cell velocity were also quantified. RESULTS: Compared with normotensive subjects, hypertensive patients showed lower mean functional capillary density at baseline (25.1 +/- 1.4 vs. 33.9 +/- 1.9 cap/mm(2), p<0.01), during post-occlusive reactive hyperemia (29.3 +/- 1.9 vs. 38.2 +/- 2.2 cap/mm(2), p<0.01) and during venous congestion responses (31.4 +/- 1.9 vs. 41.1 +/- 2.3 cap/mm(2), p<0.01). Based on the density during venous congestion, the estimated structural capillary deficit was 25.1%. Mean capillary diameters were not different at the three local points, but red blood cell velocity at baseline was significantly lower in the hypertensive group (0.98 +/- 0.05 vs. 1.17 +/- 0.04 mm/s, p<0.05). CONCLUSIONS: Patients treated for essential hypertension showed microvascular rarefaction, regardless of the type of therapy used. In addition, the reduced red blood cell velocity associated with capillary rarefaction might reflect the increased systemic vascular resistance, which is a hallmark of hypertension.

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.

Use of microcirculatory parameters to evaluate chronic venous insufficiency.

BACKGROUND: Microcirculatory impairment caused by chronic venous hypertension is usually not taken into account in chronic venous insufficiency, probably due to lack of practical means to observe it. The objective of this work was to use a new noninvasive technique to access quantitatively the cutaneous microangiopathy in female patients classified according to CEAP from C1 to C5 and matched with healthy controls. METHODS: Forty-four patients and 13 healthy subjects (112 lower limbs), with a mean age +/- SD of 48 +/- 8 years, were evaluated by using orthogonal polarization spectral (OPS) imaging. Films of the internal perimaleolar region were analyzed by the CapImage software. The microcirculatory parameters evaluated were functional capillary density (number of capillaries with flowing red blood cells/mm), capillary morphology (percentage of abnormal capillaries), diameter (microm) of dermal papilla to quantify edema, diameter of capillary bulk (microm) to assess the degree of change, and diameter capillary limb to detect enlargement. A microcirculatory index combining these five parameters was proposed with I, II, and III stages, indicating normal microcirculation, and moderate and severe microangiopathy, respectively. RESULTS: These microcirculatory parameters were significantly different (P < .05) from control values (C): capillary diameter and capillary morphology from C2 to C5, 8.1 +/- 0.8, 3.6 +/- 5.5 (C), and 9.7 +/- 1.3, 27.5 +/- 17.7 (C2); diameter of dermal papilla and diameter of capillary bulk from C3 to C5, 111.4 +/- 13.5, 52.8 +/- 8.8 (C), and 150.5 +/- 31.7, 87.8 +/- 26.9 (C3); and functional capillary density only from C4 to C5, 20.9 +/- 6.1 (C) and 14.5 +/- 4.5 (C4). The microcirculatory index showed good correlation to CEAP classification. CONCLUSION: It was possible to quantify the microangiopathy using OPS imaging and to compare the microcirculatory changes of chronic venous insufficiency patients with healthy controls. Two parameters seemed more important to identify the differences between patients and controls: capillary morphology and capillary diameter. The suggested microcirculatory index can possibly demonstrate, in future studies, a prognostic capability when combined with the CEAP classification.

Metabolic disturbances linked to obesity: the role of impaired tissue perfusion / Alterações metabólicas associadas à obesidade: o papel da disfunção da microcirculação tecidual

Associated with elevated risk of cardiovascular events and cancer, obesity is a worldwide problem affecting developed and developing countries. Microcirculatory vessels, represented by arterioles, capillaries and venules (mean internal diameter < 100 µm), are the place where blood/tissue nutrition and exchange effectively take place. Microvascular dysfunction is an early event in obesity probably secondary to endothelial dysfunction and capillaries rarefaction. New research techniques allow the investigation of the microcirculation in different vascular beds in humans. Studies suggest a link between endothelial dysfunction and visceral obesity. Oxidative stress, inflammation and rennin-angiotensin system are among factors considered to be involved on microvascular dysfunction in obesity. Microcirculatory impairment present in obesity suggests that it could be an important causal factor in obesity-related disorders such as insulin resistance and hypertension.

Associada ao aumento do risco de eventos cardiovasculares e ao câncer, a obesidade é um problema mundial, que atinge tanto países desenvolvidos quanto em desenvolvimento. A microcirculação é composta por arteríolas, capilares e vênulas (diâmetro interno médio < 100 µm) e é o local onde ocorrem a oferta de nutrientes e as trocas entre o tecido e o sangue. A disfunção microcirculatória é um evento precoce na obesidade e este pode ser secundário à disfunção endotelial ou à redução no número de capilares (rarefação capilar). Novas técnicas em pesquisa permitem a avaliação da microcirculação em diferentes leitos vasculares em humanos. Estudos sugerem uma correlação entre disfunção endotelial e obesidade visceral. Acredita-se que o estresse oxidativo, a inflamação e a atividade aumentada do sistema renina-angiotensina estão entre os fatores envolvidos nessa associação. O comprometimento microcirculatório presente na obesidade sugere que esse pode ser um fator causal importante nas desordens relacionadas com a obesidade, como resistência insulínica e hipertensão.