Metabolic flexibility associated with flight time among combat pilots of the Brazilian air force.

INTRODUCTION: Fighter pilots must support the effects of many stressors, including physical and psychological exertion, circadian disturbance, jet lag, and environmental stress. Despite the rigorous selection of military pilots, those factors predispose to failures in physiological compensatory mechanisms and metabolic flexibility. OBJECTIVES: We compared through NMR-based metabolomics the metabolic profile of Brazilian F5 fighter pilots with different flight experiences vs. the control group of non-pilots. We hypothesized that combat pilots have metabolic flexibility associated with combat flight time. METHODS: We evaluated for the first time 34 Brazilian fighter pilots from Santa Cruz Air Base (Rio de Janeiro, RJ) allocated into three groups: pilots with lower total accumulated flight experience < 1,100 h (PC1, n = 7); pilots with higher total accumulated flight experience ≥ 1,100 h (PC2, n = 6); military non-pilots (CONT, n = 21). Data collection included anthropometric measurements, total blood count, lipidogram, markers of oxidative stress, and serum NMR-based metabolomics. RESULTS: In comparison with controls (p < 0.05), pilots exhibited decreased levels of white blood cells (-13%), neutrophils (-15%), lymphocytes (-20%), alfa-glucose (-13%), lactate (-26%), glutamine (-11%), histidine (-20%), and tyrosine (-11%), but higher isobutyrate (+ 10%) concentrations. Significant correlations were found between lactate vs. amino acids in CONT (r = 0.55-0.68, p < 0.001), and vs. glutamine in PC2 (r = 0.94, p = 0.01). CONCLUSION: Fighter pilots with lower experience showed a dysregulation in immune-metabolic function in comparison with controls, which seemed to be counteracted by the accumulation of flight hours. Those findings might have implications for the health preservation and operational training of fighter pilots.

Oxygenated versus non-oxygenated flush out during deceased donor liver procurement: The first proof-of-concept study in humans.

BACKGROUND: Liver transplantation is used for treating end-stage liver disease, fulminant hepatitis, and oncological malignancies and organ shortage is a major limiting factor worldwide. The use of grafts based on extended donor criteria have become internationally accepted. Oxygenated machine perfusion technologies are the most recent advances in organ transplantation; however, it is only applied after a period of cold ischemia. Due to its high cost, we aimed to use a novel device, OxyFlush®, based on oxygenation of the preservation solution, applied during liver procurement targeting the maintenance of ATP during static cold storage (SCS). METHODS: Twenty patients were randomly assigned to the OxyFlush or control group based on a 1:1 ratio. In the OxyFlush group, the perfusion solution was oxygenated with OxyFlush® device while the control group received a non-oxygenated solution. Liver and the common bile duct (CBD) biopsies were obtained at three different time points. The first was at the beginning of the procedure, the second during organ preparation, and the third after total liver reperfusion. Biopsies were analyzed, and adenosine triphosphate (ATP) levels and histological scores of the liver parenchyma and CBD were assessed. Postoperative laboratory tests were performed. RESULTS: OxyFlush® was able to maintain ATP levels during SCS and improved the damage caused by the lack of oxygen in the CBD. However, OxyFlush® did not affect laboratory test results and histological findings of the parenchyma. CONCLUSION: We present a novel low-cost device that is feasible and could represent a valuable tool in organ preservation during SCS.

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).

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.

Effects of a high-fat meal on inflammatory and endothelial injury biomarkers in accordance with adiposity status: a cross-sectional study.

BACKGROUND: It is known that consuming a high-fat meal (HFM) induces microvascular dysfunction (MD) in eutrophic women and aggravates it in those with obesity. Our purpose was to investigate if the MD observed after a single HFM intake is caused by endothelial damage or increased inflammatory state, both determined by blood biomarkers. METHODS: Nineteen women with obesity (BMI 30-34.9 kg/m2) and 18 eutrophic ones (BMI 20.0-24.9 kg/m2) were enrolled into two groups: Obese (OBG) and Control (CG), respectively. Blood samples were collected at five-time points: before (fasting state) and 30, 60, 120, and 180 min after HFM intake to determine levels of adipokines (adiponectin, leptin), non-esterified fatty acid (NEFA), inflammatory [tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6)] and endothelium damage [soluble E-selectin, soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble intercellular adhesion molecule-1 (sICAM-1), plasminogen activator inhibitor-1 (PAI-1)] biomarkers. RESULTS: Levels of soluble E-selectin, leptin, and PAI-1 were higher in OBG at all-time points (P < 0.05) compared to CG. In the fasting state, OBG had higher levels of NEFA compared to CG (P < 0.05). In intra-group analysis, no significant change in the levels of circulating inflammatory and endothelial injury biomarkers was observed after HFM intake, independently of the group. CONCLUSION: Our findings suggest that women with obesity have an increased pro-inflammatory state and more significant endothelial injury compared to eutrophic ones. However, the consumption of a HFM was not sufficient to change circulating levels of inflammatory and endothelial injury biomarkers in either group. REGISTRATION NUMBER FOR CLINICAL TRIALS: NCT01692327.

SARS-CoV-2 infection causes pulmonary shunt by vasodilatation.

Patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may present a significant hypoxemia. The exactly mechanism of such hypoxemia in patients with coronavirus disease 2019 (COVID-19) is not well described. It has been suggested that microthrombosis contributes to this mechanism, increasing pulmonary dead space. However, dead spaces would not be sensible to oxygen supplementation, and also, enlargement of pulmonary vessels it has been evidenced. Shunt mechanism by vasodilatation, instead, could explain decubitus dependence in oxygenation by blood redistribution as observed in these patients, and moreover, would be more sensible to oxygen supplementation than dead spaces. We hypothesized that SARS-CoV-2 causes an intrapulmonary vascular dilatation (IPVD), determining a shunt mechanism by vasodilatation. We performed contrast-enhanced transthoracic echocardiography to search IPVD shunt in patients with confirmed COVID-19, hospitalized in an intensive care unit. Ten patients were recruited; one patient was excluded due to low quality of echocardiographic image, and nine patients were included. IPVD was found in seven (78%) patients, with different grades, including patient with normal compliance and the one without invasive ventilation. We demonstrated that shunt by IPVD is present among patients with COVID-19, and this mechanism is probably implicated in significant hypoxemia observed.

Dissociation between macro- and microvascular parameters in the early phase of hemorrhagic shock.

Hemorrhagic shock (HS) therapy is based on macrohemodynamic improvement, but it is not clear if this therapy correlates directly with increases in tissue perfusion. Aiming to clarify this point, we compared norepinephrine (NE, a vasoconstrictor), sodium nitroprusside (NP, a vasodilator) and levosimendan (LEV, an inodilator) treatments on macro and microvascular parameters using the hamster dorsal skinfold chamber preparation. One hour after HS, animals received Ringer's lactate (RL) solution within 10 min, then animals received RL, NP, NE and LEV during 90 min via jugular vein. Macrovascular variables: mean arterial pressure (MAP), heart rate (HR), maximal ventricle pressure (MVP), change in ventricular pressure over time (dP/dt) and microvascular variables: arteriolar and venular diameters, functional capillary density (FCD) and red blood cell velocity (RBCV) were evaluated at baseline, 60 min after HS, 60 and 90 min after treatments. Lactate blood concentrations were evaluated at baseline, 60 min after HS and 90 min after treatments. Hematocrit (Hct), cardiac output (CO), stroke volume (SV) and number of rolling and adhered leukocytes were assessed at 90 min after treatments. Data were considered significant when p < 0.05. NE increased significantly all macrohemodynamic variables compared to baseline (except MAP), and it was the only treatment that increased Hct, CO and SV significantly. NE decreased significantly all microvascular variables in comparison to baseline. NP increased HR, FCD and RBCV and reduced MVP and dP/dt significantly. LEV decreased MVP and dP/dt, arteriolar diameter and FCD and augmented RBCV significantly in comparison to baseline. Blood concentration of lactate increased significantly 60 min after HS. Leukocyte rolling and adhesion were not different between groups. We concluded that, early, during hemorrhagic shock, norepinephrine associated to fluid therapy improved macrohemodynamic parameters but failed to improved microvascular flow. Conversely, sodium nitroprusside association had the opposite effect. Despite its inodilator properties, levosimendan did not improve macro or microhemodynamic parameters when combined to fluid therapy.

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 Selenium in the Microcirculation of Fructose-Fed Hamsters.

BACKGROUND AND AIMS: Fructose intake is directly related to vascular dysfunction and it is a risk factor for the development of metabolic and cardiovascular diseases, such as obesity, diabetes, and hypertension. Selenium, a component of antioxidant enzymes, improves hyperglycemia and vascular function in diabetic animals. The aim of this study was to evaluate the effects of dietary selenium supplementation on microcirculatory and metabolic parameters of fructose-fed hamsters. METHODS AND RESULTS: Male hamsters (Mesocricetus auratus) had their drinking water substituted or not by 10% fructose solution for 60 days, during which their microcirculatory function was evaluated in the cheek pouch preparation. Blood glucose and serum insulin levels were also tested. Microcirculatory responses to acetylcholine (an endothelium-dependent vasodilator) and to sodium nitroprusside (SNP, an endothelium-independent vasodilator), and macromolecular permeability increase induced by a 30-min ischemia/reperfusion (I/R) procedure, showed that endothelium-dependent and independent vasodilatation was significantly increased in animals that had high selenium supplementation, in both the control and fructose-fed groups. Selenium supplementation protected against plasma leakage induced by I/R in all control and fructose-fed groups. CONCLUSION: Our results indicate that dietary selenium supplementation reduces microvascular dysfunction by increasing endothelial-dependent and independent dilatation and reducing macromolecular permeability increase in fructose-fed animals.

Constitutive DPP4 activity, inflammation, and microvascular reactivity in subjects with excess body weight and without diabetes.

OBJECTIVE: In patients with diabetes, dipeptidyl peptidase 4 (DPP4) inhibition is associated with attenuation of inflammation and endothelial dysfunction. Here, we investigated the associations between constitutive DPP4 activity, inflammatory biomarkers, and microvascular reactivity in subjects with excess body weight without diabetes. METHODS: Forty subjects of BMI ≥ 25.0 kg/m2 and without diabetes were cross-sectionally evaluated. We assessed microvascular blood flow and vasomotion by laser Doppler flowmetry, and measured at baseline, 30, and 60 min after a standardized meal: DPP4 activity, glucose, insulin, hs-CRP, TNF-α, IL-6, PAI-1, ICAM-1, and VCAM-1. HOMA-IR and HOMA-AD were used to assess insulin resistance. Linear correlations of DPP4 activity with the biomarkers of inflammation and components of microvascular function were conducted. In step further, multiple regression analyses were performed to test whether some of these variables could influence, or be influenced by, the plasma DPP4 activity. RESULTS: DPP4 activity was inversely associated with VCAM-1 at baseline (P < 0.05), and DPP4 activityAUC was inversely correlated with the myogenic componentAUC of vasomotion (P < 0.05). In multiple regression analysis, HOMA-AD, IL-6, VCAM-1, PAI-1, blood flow, and vasomotion influenced DPP4 activity and explained almost 40% of the variance on it. When HOMA-AD, VCAM-1, and blood flow were placed respectively as dependent variables, DPP4 activity exerted a significant effect in all of them. CONCLUSIONS: Constitutive DPP4 activity was associated with early markers of endothelial proinflammatory activation and microvascular function, and may have an influence and even be influenced by inflammation and microvascular blood flow in subjects with excess body weight without diabetes.

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).

Protective Effects of Micronized Purified Flavonoid Fraction (MPFF) on a Novel Experimental Model of Chronic Venous Hypertension.

OBJECTIVES: To assess protective effects of micronized purified flavonoid fraction (MPFF) on microcirculation in an original chronic model of hind limb venous hypertension with low blood flow in small animals. METHODS: Vein ligatures were performed on male hamsters, as follows: A-right femoral vein; A + B-right femoral vein and its right branch; A + C-right femoral vein and its left branch; A + B + C-right femoral and its right and left branches; D-external right iliac vein. In sham operated groups, similar vascular dissections were performed without ligatures. Superficial (epigastric) and central (jugular) venous pressure evaluations were made during a 10 week period. Hamsters subjected to A + B + C and D ligatures were selected for leukocyte rolling and sticking, functional capillary density (FCD), and venular and arteriolar diameter observations. D ligature was selected to evaluate pharmacological treatment efficacy. MPFF (100 mg/kg), concomitant active flavonoids of MPFF (diosmetin, hesperidin, linarin, and isorhoifolin) (10 mg/kg), diosmin (100 mg/kg) or drug vehicle were administered orally during 2 weeks before vein ligature and 6 weeks thereafter. RESULTS: A, A + B and A + C models maintained venous return through collaterals. From the 2nd to the 10th weeks after vein ligatures, A + B + C and D models elicited a progressive increase of superficial venous pressure (3.83 ± 0.65 vs. 8.56 ± 0.72 mmHg, p < .001 and 4.13 ± 0.65 vs. 9.35 ± 0.65 mmHg, p < .001, respectively) with significant changes to the microcirculation. As D model significantly increased superficial venous pressure without affecting central venous pressure, it was used to evaluate the long-term effects of treatment. Compared with vehicle, MPFF, concomitant active flavonoids of MPFF, and diosmin, significantly decreased leukocyte-endothelium interaction and prevented FCD reduction. Only MPFF significantly prevented venular enlargement as observed in the vehicle treated group. CONCLUSION: MPFF was more effective than diosmin in improving all microvascular variables. The superiority of MPFF over diosmin alone can be explained by the synergistic beneficial effects of the association between diosmin and active flavonoids of MPFF.

Microparticles derived from obese adipose tissue elicit a pro-inflammatory phenotype of CD16+, CCR5+ and TLR8+ monocytes.

Macrophage infiltration into adipose tissue (AT) is a hallmark of the chronic inflammatory response in obesity and is supported by an intense monocyte migration towards AT. Although it has been detected an increased proportion of circulating CD16+ monocyte subsets in obese subjects, the mechanisms underlying this effect and the contribution of these cells to the inflamed profile of obese AT are still poorly understood. We investigated whether factors secreted by human obese omental AT could polarize monocytes to CD16+ enriched phenotype, and how these changes could modify their migratory capacity towards adipose tissue itself. We show that explants of human obese omental AT, obtained during bariatric surgery, released higher levels of MIP1-α, TNFα, leptin and also VEGF, together with increasing amounts of microparticles (MP), when compared to explants of lean subcutaneous AT. A higher content of circulating MP derived from preadipocytes and leukocytes was also detected in plasma of obese subjects. Conditioned media or MP released from obese omental AT increased CD16 and CCR5 expression on CD14+CD16- monocytes and augmented their migratory capacity towards the conditioned media from obese omental AT, itself. This effect was inhibited when MIP1-α was neutralized. Additionally, we demonstrate that MP derived from obese omental AT carry and transfer TLR8 to monocytes, thus triggering an increase in CD16 expression in those cells. Our data shows a positive feedback loop between blood monocytes and obese omental AT, which releases chemotactic mediators and TLR8-enriched MP, thus inducing an up-regulation of CD16+ monocytes, favoring leukocyte infiltration in the obese omental AT.

Contribution of muscarinic receptors to in vitro and in vivo effects of Ruscus extract.

The objectives of this study were to evaluate, in vitro and in vivo, the contribution of muscarinic receptors to the effects of Ruscus extract. Ruscus extract was tested in competition binding experiments at recombinant human muscarinic receptors, heterologous expressed in Chinese Hamster Ovary (CHO) cells and in cellular assays measuring Ca2+ liberation and activator protein-1 (AP-1) reporter gene activation. The impact of muscarinic blockade on prolonged treatment outcome was evaluated using the hamster cheek pouch (HCP) microcirculation examining macromolecular permeability increase induced by histamine or ischemia/reperfusion (I/R), mean arteriolar and venular diameters, functional capillary density and I/R-induced leukocyte rolling and sticking. Ruscus extract exhibited affinities for muscarinic receptor subtypes at a range of 50-100µg/ml and behaved as partial agonist at human recombinant M1 and M3 receptors for Ca2+ liberation, confirmed in an AP-1 reporter gene assay. In the HCP model, topical application of atropine completely or partially blocked Ruscus extract-induced reductions of histamine- and I/R-induced increases of macromolecular permeability and leukocyte-endothelium interaction. Our results showed that Ruscus extract in vitro binds and activates different subtypes of muscarinic receptors and in vivo its anti-inflammatory effects are, at least partially, mediated via muscarinic receptors.

Ivabradine Attenuates the Microcirculatory Derangements Evoked by Experimental Sepsis.

BACKGROUND: Experimental data suggest that ivabradine, an inhibitor of the pacemaker current in sinoatrial node, exerts beneficial effects on endothelial cell function, but it is unclear if this drug could prevent microcirculatory dysfunction in septic subjects, improving tissue perfusion and reducing organ failure. Therefore, this study was designed to characterize the microcirculatory effects of ivabradine on a murine model of abdominal sepsis using intravital videomicroscopy. METHODS: Twenty-eight golden Syrian hamsters were allocated in four groups: sham-operated animals, nontreated septic animals, septic animals treated with saline, and septic animals treated with ivabradine (2.0 mg/kg intravenous bolus + 0.5 mg · kg · h). The primary endpoint was the effect of ivabradine on the microcirculation of skinfold chamber preparations, assessed by changes in microvascular reactivity and rheologic variables, and the secondary endpoint was its effects on organ function, evaluated by differences in arterial blood pressure, motor activity score, arterial blood gases, and hematologic and biochemical parameters among groups. RESULTS: Compared with septic animals treated with saline, those treated with ivabradine had greater functional capillary density (90 ± 4% of baseline values vs. 71 ± 16%; P < 0.001), erythrocyte velocity in capillaries (87 ± 11% of baseline values vs. 62 ± 14%; P < 0.001), and arteriolar diameter (99 ± 4% of baseline values vs. 91 ± 7%; P = 0.041) at the end of the experiment. Besides that, ivabradine-treated animals had less renal, hepatic, and neurologic dysfunction. CONCLUSIONS: Ivabradine was effective in reducing microvascular derangements evoked by experimental sepsis, which was accompanied by less organ dysfunction. These results suggest that ivabradine yields beneficial effects on the microcirculation of septic animals.

Microcirculatory dysfunction in sepsis: pathophysiology, clinical monitoring, and potential therapies.

Abnormal microvascular perfusion, including decreased functional capillary density and increased blood flow heterogeneity, is observed in early stages of the systemic inflammatory response to infection and appears to have prognostic significance in human sepsis. It is known that improvements in systemic hemodynamics are weakly correlated with the correction of microcirculatory parameters, despite an appropriate treatment of macrohemodynamic abnormalities. Furthermore, conventional hemodynamic monitoring systems available in clinical practice fail to detect microcirculatory parameter changes and responses to treatments, as they do not evaluate intrinsic events that occur in the microcirculation. Fortunately, some bedside diagnostic methods and therapeutic options are specifically directed to the assessment and treatment of microcirculatory changes. In the present review we discuss fundamental aspects of septic microcirculatory abnormalities, including pathophysiology, clinical monitoring, and potential therapies.

Dynamic nailfold videocapillaroscopy may be used for early detection of microvascular dysfunction in obesity.

OBJECTIVES: It has been hypothesized that obesity is the primary cause of microvascular dysfunction (MD), which could be a pathway to increase blood pressure and decrease insulin sensitivity. Due to the high prevalence of this metabolic disorder in the world today, the aim of this study was to investigate which is the most appropriate videocapillaroscopic method, between nailfold and dorsal finger, to assess microvascular function in obese patients since both techniques are non-invasive and could be used for early detection as well as for follow-up. METHODS: Eighteen lean [27.8±6.2years, body mass index (BMI) 21.8±1.8kg/m(2)] and nineteen obese (30.8±4.6years; BMI 32.3±1.5kg/m(2)) women participated in the study. Dynamic nailfold videocapillaroscopy assessed morphological (capillary diameters) and functional [functional capillary density (FCD); red blood cell velocity (RBCV) at baseline and peak and time (TRBCVmax) taken to reach it during the post-occlusive reactive hyperemia (PORH) response, after 1-min ischemia] parameters; while dorsal finger videocapillaroscopy assessed FCD at rest and capillary recruitment during PORH and post-venous occlusion. RESULTS: RBCV (0.32±0.01 vs. 0.30±0.01mm/s; p<0.0001) and RBCVmax (0.32±0.01 vs. 0.30±0.015mm/s; p=0.0020) were significantly higher in control subjects compared to the obese group. Moreover, TRBCVmax was prolonged in the obese group compared to control one (3.5±1.4 vs. 5.5±1.3s; p=0.0001). Multiple regression analysis showed that these variables were influenced by some others, especially those related to adiposity and metabolic disease. On the other hand, dorsal finger videocapillaroscopy did not show any significant differences between groups. CONCLUSION: Our results strongly suggest that microvascular dysfunction consequent to obesity could be better detected by dynamic nailfold videocapillaroscopy than by dorsal finger videocapillaroscopy.

Short-Term Resistance Training Attenuates Cardiac Autonomic Dysfunction in Obese Adolescents.

PURPOSE: Cardiac autonomic dysfunction (CADysf) in children is often associated to obesity and may be attenuated by physical activity. In this study, we investigated the effects of resistance training (RT) upon CADysf assessed by heart rate variability (HRV) in obese adolescents. METHOD: Volunteers were assigned into groups according to standard deviation scores for body mass index (z-BMI) and percentile for age and sex: obese (OB; z-BMI from 2 to 3 and ≥ 95th percentile, n = 24) and normal weight controls (CG; z-BMI from -2-1 and < 85th percentile, n = 20). OB performed isolated RT during 12 weeks [3 sets of 6-10reps with 70-85% 10RM]. Waist circumference, systolic/diastolic blood pressures (SBP/DBP), lipids, and HRV were assessed at baseline. Only OB underwent postintervention assessments. RESULTS: At baseline, SBP (122.4 ± 9.1 vs. 109.7 ± 11.5 mmHg, p < .001) and DBP (76.1 ± 7.1 vs. 65.3 ± 5.9 mmHg, p < .001) were higher, while parasympathetic HRV indexes were lower (p < .05) in OB compared with CG. After RT, waist circumference (3%, p < .001) and SBP (10%, p < .001) reduced in OB. Parasympathetic indexes of HRV increased in OB (SDNN: 25%, p = .03; rMSSD: 48%, p = .0006; pNN50: 67%, p = .001; total power: 54%, p = .01; HF: 101%, p = .001) and baseline differences between groups for sympathetic and parasympathetic activities were no longer observed after RT. CONCLUSION: RT attenuated CAdyfs and BP in obese adolescents, by increasing parasympathetic activity and decreasing sympatho-vagal balance.

Health markers in obese adolescents improved by a 12-week recreational soccer program: a randomised controlled trial.

The effects of a recreational soccer program (RSP) upon body composition, heart rate variability (HRV), biochemical markers, cardio-respiratory fitness, and endothelial function in obese adolescents were investigated. A randomised controlled clinical trial was conducted with 30 adolescents aged 12-17 years and body mass index (BMI) >2 standard deviations of WHO reference values, which were assigned to RSP (n = 10, 2 girls) and obese control (n = 10, 4 girls) groups. The 12-week RSP included 60-min sessions performed 3 times/week. BMI, waist circumference, blood pressure, blood glucose, lipid profile, insulin, C-reactive protein, HRV, and maximal oxygen consumption (VO2peak) were evaluated following standardised procedures. Body composition was determined by dual-energy X-ray absorptiometry and endothelial function by venous occlusion plethysmography. After intervention, RSP exhibited significant reductions in BMI (-0.7 ± 0.2 kg · m(-2)), waist circumference (-8.2 ± 1.4 cm), %body fat (-2.2 ± 0.4%), systolic blood pressure (-5.0 ± 2.3 mmHg), total cholesterol (-16.2 ± 5.8 mg · dL(-1)), triglycerides (-20.5 ± 12.9 mg · dL(-1)), C-reactive protein (-0.06 ± 0.01 mg · dL(-1)), insulin resistance (HOMA-IR, -1.4 ± 0.6), and sympathetic activity (LF, -13.9 ± 6.6 un) vs. controls (P < 0.05). Significant increase was observed in parasympathetic activity (HF, 13.9 ± 6.6 un), VO2peak (7.9 ± 2.8 ml · kg(-1) · min(-1)), and high-density lipoprotein cholesterol (11.0 ± 6.3 mg · dL(-1)) (P < 0.05). Vascular conductance (19.5 ± 8.1 ml · min(-1) · 100 ml, P = 0.005) increased and vascular resistance (-5.9 ± 2.4 ml · min(-1) · 100 ml, P = 0.041) decreased in RSP, but not in controls. A 12-week recreational soccer intervention was effective to improve biochemical, cardiovascular, and fitness health markers in obese adolescents.

Dexmedetomidine attenuates the microcirculatory derangements evoked by experimental sepsis.

BACKGROUND: Dexmedetomidine, an α-2 adrenergic receptor agonist, has already been used in septic patients although few studies have examined its effects on microcirculatory dysfunction, which may play an important role in perpetuating sepsis syndrome. Therefore, the authors have designed a controlled experimental study to characterize the microcirculatory effects of dexmedetomidine in an endotoxemia rodent model that allows in vivo studies of microcirculation. METHODS: After skinfold chamber implantation, 49 golden Syrian hamsters were randomly allocated in five groups: (1) control animals; (2) nonendotoxemic animals treated with saline; (3) nonendotoxemic animals treated with dexmedetomidine (5.0 µg kg h); (4) endotoxemic (lipopolysaccharide 1.0 mg/kg) animals treated with saline; and (5) endotoxemic animals treated with dexmedetomidine. Intravital microscopy of skinfold chamber preparations allowed quantitative analysis of microvascular variables and venular leukocyte rolling and adhesion. Mean arterial blood pressure, heart rate, arterial blood gases, and lactate concentrations were also documented. RESULTS: Lipopolysaccharide administration increased leukocyte rolling and adhesion and decreased capillary perfusion. Dexmedetomidine significantly attenuated these responses: compared with endotoxemic animals treated with saline, those treated with dexmedetomidine had less leukocyte rolling (11.8 ± 7.2% vs. 24.3 ± 15.0%; P < 0.05) and adhesion (237 ± 185 vs. 510 ± 363; P < 0.05) and greater functional capillary density (57.4 ± 11.2% of baseline values vs. 45.9 ± 11.2%; P < 0.05) and erythrocyte velocity (68.7 ± 17.6% of baseline values vs. 54.4 ± 14.8%; P < 0.05) at the end of the experiment. CONCLUSIONS: Dexmedetomidine decreased lipopolysaccharide-induced leukocyte-endothelial interactions in the hamster skinfold chamber microcirculation. This was accompanied by a significant attenuation of capillary perfusion deficits, suggesting that dexmedetomidine yields beneficial effects on endotoxemic animals' microcirculation.