Skin Microvascular Blood Flow Research Articles

Enhancing Endothelial Function with Nutrient-Enriched Table Hen Eggs: A Randomized Study in Patients Recovering from Acute Coronary Syndrome.

This study investigated the effect of consumption of table eggs enriched with n-3 polyunsaturated fatty acids (n-3 PUFA), lutein, vitamin E and selenium on microvascular function, oxidative stress and inflammatory mediators in patients after acute coronary syndrome (ACS). In a prospective, randomized, interventional, double-blind clinical trial, ACS patients were assigned to either the Nutri4 (N=15, mean age: 57.2±9.2 years), or the Control group (N=13; mean age 56.8±9.6 years). The Nutri4 group consumed three enriched hen eggs daily for three weeks, providing approximately 1.785 mg of vitamin E, 0.330 mg of lutein, 0.054 mg of selenium and 438 mg of n-3 PUFAs. Biochemical parameters, including serum lipids, liver enzymes, nutrient concentrations, serum antioxidant enzyme activity (catalase (CAT), glutathione peroxidase (GPx), superoxide dismutase (SOD)), and markers of oxidative stress (thiobarbituric acid reactive substances (TBARS) and ferric reducing ability (FRAP)), were assessed before and after the dietary interventions. Additionally, arterial blood pressure, heart rate, body composition, fluid status, anthropometric measurements, and skin microvascular blood flow responses to various stimuli (postocclusive reactive hyperemia (PORH), acetylcholine- (AchID), and sodium nitroprusside- (SNPID)) were measured using laser Doppler flowmetry (LDF) throughout the study. The intake of Nutri4 eggs led to a significant reduction in LDL cholesterol levels, while the levels of total cholesterol remained within the established reference values. Consuming Nutri4 eggs resulted in a 12.7% increase in serum vitamin E levels, an 8.6% increase in selenium levels, and demonstrated a favorable impact on microvascular reactivity, as evidenced by markedly improved PORH and ACh ID. Nutri4 eggs exerted a significant influence on the activity of GPx and SOD, with no observed changes in TBARS or FRAP values. The consumption of Nutri4 eggs positively influenced microvascular function in individuals with ACS, without eliciting adverse effects on oxidative stress.

Effects of Voluntary Changes in Minute Ventilation on Microvascular Skin Blood Flow

Effects of Voluntary Changes in Minute Ventilation on Microvascular Skin Blood Flow

Reversible skin microvascular hyporeactivity in patients with immune-mediated thrombocytopenic thrombotic purpura

BackgroundImmune-mediated thrombotic thrombocytopenic purpura (iTTP) is a rare disease characterized by arteriolar and capillary microthrombosis precipitating organ failure. However, the contribution of endothelial dysfunction on impaired microvascular blood flow in iTTP patients has been poorly explored. This pilot observational study aimed to explore endothelial-mediated vasoreactivity in iTTP patients at admission and its changes after plasma exchange therapy (PE).MethodsWe conducted a prospective observational study in patients (> 18-year old) admitted in ICU for iTTP. Using laser Doppler flowmetry and acetylcholine (Ach) iontophoresis in the forearm, we recorded the skin microvascular blood flow and the endothelium-mediated vasoreactivity at admission and after PE. Demographics, biological, clinical courses, and outcomes were also collected. As a control group, we used a previously published cohort of young diabetic patients after correction of ketoacidosis.ResultsEighteen confirmed iTTP patients and 34 controls were included in the study, mainly female (72%) aged 43 ± 16-year-old. At admission, 55% had neurological abnormalities, 50% cardiac issues and 27.8% an acute kidney injury. Median platelet count was 19 G/mL [10–37]. Baseline microvascular blood flow was decreased in iTTP patients when compared to controls (5.97 ± 4.5 vs. 10.1 ± 6.3 PU, P = 0.03), associated with markedly impaired endothelial-mediated skin microvascular reactivity (AUC: 9627 ± 8122 vs. 16,475 ± 11,738, P = 0.03). Microvascular reactivity improved after the first PE session (AUC: 9627 ± 8122 vs 16,558 ± 10,699, P = 0.007, respectively, baseline and post-PE1) and much more after the second session (26,431 ± 23,181, P = 0.04 post-PE1 vs post-PE2). Hemolysis biomarkers (LDH and bilirubin) negatively correlated with skin microvascular flow and vasoreactivity.ConclusionWe highlighted a marked yet reversible skin endothelium-mediated microvascular hyporeactivity in iTTP patients that could participate in organ injury pathophysiology.

Impaired skin microvascular endothelial reactivity in critically ill COVID-19 patients

BackgroundSome clinical and histological studies have reported that SARS-CoV-2 infection may damage the endothelium. However, the impact of this virus on endothelial function in vivo remains poorly characterized. In this single-center pilot observational study, we performed iontophoresis of acetylcholine coupled with Laser doppler to investigate microvascular endothelial reactivity in COVID-19 patients compared to patients with non-COVID-19 bacterial pneumonia (NCBP) patients.ResultsDuring three consecutive months, 32 COVID-19 patients and 11 control NCBP patients with acute respiratory failure were included. The median age was 59 [50–68] and 69 [57–75] years in COVID-19 and NCBP groups, respectively (P = 0.11). There was no significant difference in comorbidities or medications between the two groups, except for body mass index, which was higher in COVID-19 patients. NCBP patients had a higher SAPS II score compared to COVID-19 patients (P < 0.0001), but SOFA score was not different between groups (P = 0.51). Global hemodynamic and peripheral tissue perfusion parameters were not different between groups. COVID-19 patients had significantly lower skin microvascular basal blood flow than NCBP patients (P = 0.02). In addition, endothelium-dependent microvascular reactivity was threefold lower in COVID-19 patients than NCBP patients (P = 0.008).ConclusionsBoth baseline skin microvascular blood flow and skin endothelial-dependent microvascular reactivity were impaired in critically ill COVID-19 patients compared to NCBP patients, despite a lower disease severity score supporting a specific pathogenic role of SARS-CoV-2 on the endothelium.

Drag-Reducing Polymers Improve Vascular Hemodynamics and Tissue Oxygen Supply in Mouse Model of Diabetes Mellitus.

Diabetes mellitus (DM) is a chronic metabolic disease characterised by hyperglycaemia and glucose intolerance caused by impaired insulin action and/or defective insulin secretion. Long-term hyperglycaemia leads to various structural and functional microvascular changes within multiple tissues, including the brain, which involves blood-brain barrier alteration, inflammation and neuronal dysfunction. We have shown previously that drag-reducing polymers (DRP) improve microcirculation and tissue oxygen supply, thereby reducing neurologic impairment in different rat models of brain injury. We hypothesised that DRP could improve cerebral and skin microcirculation in the situation of progressive microangiopathies associated with diabetes using a mouse model of diabetes mellitus. Diabetes was induced in C57BL/6 J mice with five daily consecutive intraperitoneal injections of streptozotocin (50mg/kg/day). Animals with plasma glucose concentrations greater than 250mg/dL were considered diabetic and were used in the study following four months of diabetes. DRP (2ppm) was injected biweekly during the last two weeks of the experiment. Cortical and skin (ear) microvascular cerebral blood flow (mCBF) and tissue oxygen supply (NADH) were measured by two-photon laser scanning microscopy (2PLSM). Cerebrovascular reactivity (CVR) was evaluated by measuring changes in arteriolar diameters and NADH (tissue oxygen supply) during the hypercapnia test. Transient hypercapnia was induced by a 60-second increase of CO2 concentration in the inhalation mixture from 0% to 10%. Compared to non-diabetic animals, diabetic mice had a significant reduction in the density of functioning capillaries per mm3 (787±52 vs. 449±25), the linear velocity of blood flow (1.2±0.31 vs. 0.54±0.21mm/sec), and the tissue oxygen supply (p<0.05) in both brain and skin. DRP treatment was associated with a 50% increase in all three parameters (p<0.05). According to the hypercapnia test, CVR was impaired in both diabetic groups but more preserved in DRP mice (p<0.05). Our study in a diabetic mouse model has demonstrated the efficacy of hemorheological modulation of blood flow by DRP to achieve increased microcirculatory flows and tissue oxygen supply.

Does the Endothelium of Competitive Athletes Benefit from Consumption of n-3 Polyunsaturated Fatty Acid-Enriched Hen Eggs?

The present study aimed to determine the effect of n-3 polyunsaturated fatty acid (PUFA)-enriched hen eggs on microvascular vasodilation, microvascular responsiveness to a stress challenge and markers of oxidative stress in competitive athletes. Competitive athletes (n=23) were divided to a control group (n=9), who consumed three regular hens’ eggs daily (249 mg n-3 PUFAs/d), and n-3 PUFAs group (n=14), who consumed three n-3 PUFA-enriched hen eggs daily (1,053 g n-3 PUFAs/d) for 3 weeks. Endothelium-dependent responses [post-occlusive reactive hyperemia (PORH) and acetylcholine-induced dilation (AChID)] and endothelium-independent responses [sodium nitroprusside-induced dilation (SNPID)] of skin microvascular blood flow were assessed by laser Doppler flowmetry in pre- and post-acute exhausting exercise (AEE) sessions. Blood pressure, serum lipid, free fatty acids profiles, and biomarkers of oxidative stress were measured before and after each dietary protocol. Consumption of serum n-3 PUFAs significantly decreased the n-6/n-3 ratio and enhanced PORH and AChID, but did not affect SNPID at rest. Furthermore, serum glutathione peroxidase and superoxide dismutase activities were significantly decreased in the n-3 PUFAs group but remained unchanged in the control group. In both groups, PORH, AChID, and SNP were significantly reduced post-AEE compared with pre-AEE, both before and after consumption of each diet. Only AChID responsiveness to AEE (ΔAChID) significantly increased following consumption of n-3 PUFAs. Overall, n-3 PUFAs supplementation as n-3 PUFA-enriched hen eggs enhanced microvascular endothelial function at rest and may contribute to adaptation to AEE in competitive athletes.

Dynamics of skin microvascular blood flow in 4-6-year-old children in association with pre- and postnatal black carbon and particulate air pollution exposure.

A growing body of evidence indicates that cardiovascular health in adulthood, particularly that of the microcirculation, could find its roots during prenatal development. In this study, we investigated the association between pre- and postnatal air pollution exposure on heat-induced skin hyperemia as a dynamic marker of the microvasculature. In 139 children between the ages of 4 and 6 who are followed longitudinally within the ENVIRONAGE birth cohort, we measured skin perfusion by Laser Doppler probes using the Periflux6000. Residential black carbon (BC), particulate (PM10 and PM2.5) air pollution, and nitrogen dioxide (NO2) levels were modelled for each participant's home address using a high-resolution spatiotemporal model for multiple time windows. We assessed the association between skin hyperemia and pre- and postnatal air pollution using multiple regression models while adjusting for relevant covariates. Residential BC exposure during the whole pregnancy averaged (IQR) 1.42 (1.22-1.58) µg/m3, PM10 18.88 (16.64 - 21.13) µg/m3, PM2.5 13.67 (11.5 - 15.56) µg/m3 and NO2 18.39 (15.52 - 20.31) µg/m3. An IQR increment in BC exposure during the third trimester of pregnancy was associated with an 11.5 % (95% CI: -20.1 to -1.9; p=0.020) lower skin hyperemia. Similar effect estimates were retrieved for PM10, PM2.5 and NO2 (respectively 13.9 % [95% CI: -21.9 to -3.0; p=0.003], 17.0 % [95% CI: -26.7 to -6.1; p=0.004] and 12.7% [95 % CI: -22.2 to -1.9; p=0.023] lower skin hyperemia). In multipollutant models, PM2.5 showed the strongest inverse association with skin hyperemia. Postnatal exposure to BC, PM10, PM2.5 or NO2, was not associated with skin hyperemia at the age of 4 to 6, and did not alter the previous reported prenatal associations when taken into account. Our findings support that BC, particulate air pollution, and NO2 exposure, even at low concentrations, during prenatal life, can have long-lasting consequences for the microvasculature. This proposes a role of prenatal air pollution exposures over and beyond postnatal exposure in the microvascular alterations which were persistent into childhood.

Study Protocol: A 2-Month Cross-Over Controlled Feeding Trial Investigating the Effect of Animal and Plant Protein Intake on the Metabolome and Cardiometabolic Health

ObjectivesA dietary shift in favor of plant protein (PP) sources over animal protein (AP) sources has been advocated for both sustainability and health reasons, this dietary transition being noticeably associated to decreased cardiovascular and diabetes risks. The differences in amino acid composition between PP and AP may have several effects on the metabolic pathways, and in turn health impacts, which are still poorly characterized. This project aims at characterizing, with a combination of “omics” approaches, the metabolic reorientations induced by a dietary shift from AP to PP sources and understanding their health effects in a population at cardiometabolic risk. MethodsWe will conduct a cross-over randomized feeding trial (NCT04236518) in 20 healthy overweight males (BMI 25–35), aged 25–55, with an enlarged waist circumference (> 94cm) and high plasma triglycerides (>1.5g/L). Participants will be assigned for 1 month each to 2 diets containing predominantly either AP (65% AP:35% PP) or PP (35% AP:65% PP) in a randomized order, separated by a 2-week wash-out period. Lunch and diner will be directly provided while dietary guidelines will be given for breakfast and snacks. Blood, urine and stool samples will be collected at the fasted state every 2 weeks. At the end of each dietary intervention, blood and urine will be collected following a high fat meal, which challenges metabolism and vascular homeostasis. Plasma and urine non-targeted metabolomics analyses (LC-MS) will be combined with Peripheral Blood Mononuclear Cell (PBMC) transcriptomics and fluxomics analyses (D2O tracer) to get a comprehensive overview of the metabolic phenotype associated with AP or PP intake. Flow-Mediated Dilatation (FMD) and Flow Laser Doppler (FLD) will be used to measure respectively macrovascular endothelial function and microvascular skin blood flow at the fasted state and after the high-fat meal. We will also measure anthropometric parameters and analyze biochemistry and inflammatory markers. ResultsNot applicable (protocols abstract). ConclusionsWe expect the multi-omics fingerprinting to reveal subtle metabolic differences associated to AP or PP intake, with a positive effect of PP intake. Improved inflammatory status and endothelial function are also expected to be associated to PP intake. Funding SourcesINRAE and Roquette Frères.

N-3 POLYUNSATURATED FATTY ACIDS ENRICHED HEN EGGS CONSUMPTION ENHANCES MICROVASCULAR ENDOTHELIAL FUNCTION IN PROFESSIONAL ATHLETES

Objective: We reported previously that consumption of n-3 polyunsaturated fatty acids (n-3 PUFAs) enriched hen eggs (777 mg of n-3 PUFAs per day for three weeks) enhances forearm skin microvascular reactivity to vascular occlusion (post occlusion reactive hyperemia; PORH), and decreases arterial blood pressure (BP), serum triglycerides and high sensitivity C reactive protein (hsCRP) level in healthy individuals. Present study aimed to determine the effect of n-3 PUFAs enriched hen eggs consumption on microvascular reactivity in professional athletes. Design and method: 23 young healthy professional athletes (3 women and 20 men, age ranged 18–28 years) have consumed three standard hen eggs per day (249 mg of n-3 PUFAs/day) (Control group) or three n-3 PUFAs enriched hen eggs per day (1053 mg of n-3 PUFAs/day) (n-3 PUFA group) for three weeks. Forearm skin microvascular blood flow in response to vascular occlusion (PORH) and iontophoresis of acetylcholine (ACh) (endothelium-dependent vasodilation) and sodium nitroprusside (SNP) (endothelium-independent vasodilation) were assessed using laser Doppler flowmetry before and after diet protocols. Body mass index (BMI), waist-to-hip ratio (WHR), BP, fasting lipid panels, fasting blood glucose (fBG) and hsCRP were measured in all subjects before and after diet protocols. Results: BMI, WHR, BP, fasting lipid panels, fBG and hsCRP were not significantly changed after consumption of either eggs compared to baseline measurements within n-3 PUFAs or Control group. Consumption of n-3 PUFAs eggs significantly improved PORH and ACh-induced dilation (AChID) compared to baseline measurement within n-3 PUFAs group. Contrary, consumption of standard eggs did not induce any significant change in PORH and AChID compared to baseline in Control group. SNP-induced dilation was similar before and after respective diet protocol in both Control and n-3 PUFA groups. Conclusions: This is the first study to demonstrate that consumption of n-3 PUFAs enriched functional food (hen eggs) for three weeks enhances skin endothelium-dependent microvascular reactivity in professional athletes. This result provides foundation for future investigation of potential mechanisms by which n-3 PUFAs could improve endothelial function, and overall vascular adaptation to regular physical activity in professional athletes.

Impairment of microvascular blood flow in patients with type 2 diabetes and cardiovascular autonomic neuropathy

BACKGROUND: Diabetic autonomic neuropathy is the reason for early morbidity and mortality on diabetic patients. The pathology not only cardiac innervation but microvascular is presented.AIMS: We estimated the parameters of skin microvascular blood flow in accordance with cardiovascular autonomic neuropathy (CAN) staging in diabetic patients. We also assessed other risk factors of CAN in patients with diabetes.MATERIALS AND METHODS: We included 76 patients with type 2 diabetes in the study (24 patients with resent-onset diabetes and/or diabetes without microvascular complications, 26 with diabetic sensorimotor neuropathy (SMN) and 26 with SMN and previous history of diabetic foot amputation). The SMN was diagnosed on the basis of patients complaints, anamnesis and data of clinical neurological examinations. CAN was detected using several cardiovascular autonomic reflex tests (CART) as a gold standard of diagnosis: the tilt-table test, a deepbreathing and Valsalva Maneuver, handgrip test, cold-stress vasoconstriction. According to the Toronto Diabetic Neuropathy Expert Group Recommendation all patients was separated on the groups: CAN 0 (all CARTs were normal), CAN 1 (possible/early CAN — one abnormal CART was presented), CAN 2 (definite/confirmed CAN –at least two abnormal CARTs were found), CAN 3 (severe/advanced CAN — in the cases of orthostatic hypotension in addition to CARTs abnormalities). Microvascular blood flow of skin at the nail roller of fingers skin was valuated at rest as well as in functional cold test by the method of High-frequency Ultrasonic Dopplerography using the “Minimax Doppler K” device (LLC JV “Minimax”, St. Petersburg, Russia).RESULTS: CAN 1 was found in 8% diabetic patients without microvascular complications, 42 and 21% patients with SMN and diabetic foot amputations respectively. CAN 2 was diagnosed in 27% patients with SMN and 58% patients history of diabetic foot amputations. CAN 3 in 8% and 19% cases in patients with SMN and history of diabetic foot amputations respectively. The parameters of microvascular blood flow at rest were significantly decreased in patients with confirmed/severe CAN in comparison with early staging of CAN and patients without CAN (Vm=2.5±0.66 sm/sec vs. 4.4±0.54 sm/sec and 5.1±1.01 sm/sec respectively; p=0.0033). The abnormal result of cold test was detected in 94% patients with confirmed/ severe CAN and 26% patients with CAN 1.CONCLUSIONS: This investigation has demonstrated in a cohort with type 2 diabetes patients with/without SMN and with/ without history of previously foot amputations that decrease the Vm (the variable of microvascular blood flow assessed by High-frequency Ultrasonic Dopplerography) lower than 2.4 sm/sec is associated with 6.4 times increased likelihood of confirmed/severe CAN as well as positive cold test result. That the patients with positive cold test results were 28.6 times more likely have confirmed/severe CAN.

Exaggerated Microvascular Vasodilating Responses in Cirrhotic Patients With Septic Shock.

Cirrhosis is associated with hemodynamic and vascular disorders. However, microvascular reactivity of cirrhotic patients in the context of sepsis has poorly been investigated. Prospective observational study. Medical ICU in a tertiary teaching hospital. We prospectively included adult patients admitted in the ICU for septic shock with and without cirrhosis. After initial resuscitation, global hemodynamic parameters were recorded and skin microvascular reactivity to local acetylcholine iontophoresis was measured. None. Thirty patients with septic shock were included (60% male), 10 with cirrhosis and 20 without, with a median age of 61 years (54-74 yr). Cirrhotic patients were mainly classed as Child-Pugh C (80%) and all of them had ascites. Sequential Organ Failure Assessment score and ICU mortality of cirrhotic patients were higher than the noncirrhotic patients, respectively (6.5 [5.0-8.3] vs 11.5 [9.0-14.0]; p < 0.01; 15% vs 70%; p < 0.01). Peripheral tissue perfusion and global hemodynamic parameters were not different between the cirrhotic and noncirrhotic patients but arterial lactate level was three times higher in patients with cirrhosis (6.0 mmol/L [3.9-8.0 mmol/L] vs 2.0 mmol/L [0.9-3.5 mmol/L]; p < 0.01). Basal skin microvascular blood flow was not statistically different between the groups (4.94 perfusion units [3.45-8.73 perfusion units] vs 6.95 perfusion units [5.24-8.38 perfusion units]; p = 0.29). After acetylcholine simulation, skin microvascular blood flow increased more in cirrhotic patients than in noncirrhotic patients (644% [217-966%] vs 169% [73-505%], p = 0.03). Global microvascular reactivity was seven times higher in cirrhotic patients (area under the curve, 16,412 perfusion units [13,898-19,041 perfusion units] vs 2,664 perfusion units [969-4,604 perfusion units]; p < 0.001). We identified an exaggerated vasodilating microvascular response in cirrhotic patients with septic shock. Such a result may explain vasopressor resistance and paves the way for future therapeutic trials, targeting nitric oxide pathway specifically in this population.

Нарушение микроциркуляторного кровотока у больных сахарным диабетом 2 типа и кардиоваскулярной автономной нейропатией

BACKGROUND : Diabetic autonomic neuropathy is the reason for early morbidity and mortality on diabetic patients. The pathology not only cardiac innervation but microvascular is presented. AIMS : We estimated the parameters of skin microvascular blood flow in accordance with cardiovascular autonomic neuropathy (CAN) staging in diabetic patients. We also assessed other risk factors of CAN in patients with diabetes. MATERIALS AND METHODS : We included 76 patients with type 2 diabetes in the study (24 patients with resent-onset diabetes and/or diabetes without microvascular complications, 26 with diabetic sensorimotor neuropathy (SMN) and 26 with SMN and previous history of diabetic foot amputation). The SMN was diagnosed on the basis of patients complaints, anamnesis and data of clinical neurological examinations. CAN was detected using several cardiovascular autonomic reflex tests (CART) as a gold standard of diagnosis: the tilt-table test, a deepbreathing and Valsalva Maneuver, handgrip test, cold-stress vasoconstriction. According to the Toronto Diabetic Neuropathy Expert Group Recommendation all patients was separated on the groups: CAN 0 (all CARTs were normal), CAN 1 (possible/early CAN — one abnormal CART was presented), CAN 2 (definite/confirmed CAN –at least two abnormal CARTs were found), CAN 3 (severe/advanced CAN — in the cases of orthostatic hypotension in addition to CARTs abnormalities). Microvascular blood flow of skin at the nail roller of fingers skin was valuated at rest as well as in functional cold test by the method of High-frequency Ultrasonic Dopplerography using the “Minimax Doppler K” device (LLC JV “Minimax”, St. Petersburg, Russia). RESULTS : CAN 1 was found in 8% diabetic patients without microvascular complications, 42 and 21% patients with SMN and diabetic foot amputations respectively. CAN 2 was diagnosed in 27% patients with SMN and 58% patients history of diabetic foot amputations. CAN 3 in 8% and 19% cases in patients with SMN and history of diabetic foot amputations respectively. The parameters of microvascular blood flow at rest were significantly decreased in patients with confirmed/severe CAN in comparison with early staging of CAN and patients without CAN (Vm=2.5±0.66 sm/sec vs. 4.4±0.54 sm/sec and 5.1±1.01 sm/sec respectively; p=0.0033). The abnormal result of cold test was detected in 94% patients with confirmed/ severe CAN and 26% patients with CAN 1. CONCLUSIONS : This investigation has demonstrated in a cohort with type 2 diabetes patients with/without SMN and with/ without history of previously foot amputations that decrease the Vm (the variable of microvascular blood flow assessed by High-frequency Ultrasonic Dopplerography) lower than 2.4 sm/sec is associated with 6.4 times increased likelihood of confirmed/severe CAN as well as positive cold test result. That the patients with positive cold test results were 28.6 times more likely have confirmed/severe CAN.

Dynamics of skin microvascular blood flow in 4-6 year old children in association with pre- and postnatal black carbon and particulate air pollution exposure

Background: A growing body of evidence shows that cardiovascular disease in adulthood, in particular that of the microcirculation, could find its roots during prenatal development. In this study we investigated the association between pre- and postnatal black carbon and particulate air pollution exposure on heat-induced skin hyperemia as a dynamic marker of the microvasculature. Methods: In 139 children between the age of 4 to 6 who are followed longitudinally within the ENVIRONAGE birth cohort, we measured skin perfusion by Laser Doppler probes using the Periflux6000. Residential black carbon (BC) and particulate (PM10 and PM2.5) air pollution levels were modelled for each participant’s home address using a high-resolution spatiotemporal model. We assessed the association between skin hyperemia and pre- and postnatal air pollution using linear regression models while adjusting for relevant covariates. Results: Prenatal residential BC exposure averaged (IQR) 1.38 (1.05 - 1.62) µg/m³, PM10 18.72 (14.44 - 22.78) µg/m³ and PM2.5 13.43 (9.19 - 17.26) µg/m³. An IQR increment in BC exposure during the third trimester of pregnancy was associated with a 13.8 % (95% CI: -22.7 to -3.9; p = 0.008) lower skin hyperemia. Similar effect estimates were retrieved for PM10 and PM2.5 (respectively 11.7 % (95% CI: -20.6 to -1.8; p = 0.022) and 14.2 % (95% CI: -25.1 to -1.8; p = 0.027) lower skin hyperemia). Postnatal exposure to BC, PM10 or PM2.5 was not associated with skin hyperemia at the age 4 to 6 and did not alter the previous reported prenatal associations. Conclusion: These findings support that BC and particulate air pollution exposure even at low concentrations during prenatal life can have long-lasting consequences on the microvasculature. This proposes a role of prenatal air pollution exposures in the microvascular origin of cardiovascular disease development later in life.

Seven-Day Salt Loading Impairs Microvascular Endothelium-Dependent Vasodilation without Changes in Blood Pressure, Body Composition and Fluid Status in Healthy Young Humans

Objectives: We aimed to assess whether a 7-day high-salt (HS) diet affects endothelium-dependent and/or endothelium-independent microvascular function in the absence of changes in arterial blood pressure (BP), and to determine whether such microvascular changes are associated with changes in body composition and fluid status in healthy young humans. Materials and Methods: Fifty-three young healthy individuals (28 women and 25 men) were assigned to a 7-day low-salt diet (<3.5 g salt/day) followed by a 7-day HS diet (∼14 g salt/day). Skin microvascular blood flow in response to iontophoresis of acetylcholine (ACh) and sodium nitroprusside (SNP) was assessed by laser Doppler flowmetry, and BP, heart rate (HR), plasma renin activity (PRA), serum aldosterone, serum and 24 h-urine sodium, potassium, urea and creatinine levels, together with body composition and fluid status measurement with a 4-terminal portable impedance analyzer were measured before and after diet protocols. Results: BP, HR, body composition and fluid status were unchanged, and PRA and serum aldosterone level were significantly suppressed after HS diet. ACh-induced dilation (AChID) was significantly impaired, while SNP-induced dilation was not affected by HS diet. Impaired AChID and increased salt intake, as well as impaired AChID and suppressed renin-angiotensin system were significantly positively correlated. Changes in body composition and fluid status parameters were not associated with impaired AChID. Conclusion: 7-day HS diet impairs microvascular reactivity by affecting its endothelium-dependent vasodilation in young healthy individuals. Changes are independent of BP, body composition changes or fluid retention, but are the consequences of the unique effect of HS on endothelial function.

IS THERE A SEX-RELATED DIFFERENCE IN ENDOTHELIUM-DEPENDENT MICROVASCULAR RESPONSE TO ACUTE SALT LOADING IN YOUNG HEALTHY INDIVIDUALS?

Objective: We have earlier reported that acute salt loading affects acetylcholine (ACh) induced vasodilation (endothelium-dependent) in forearm skin microcirculation in young healthy women independently of blood pressure (BP) changes. The aim of the present study was to test is there a sex-related difference in endothelium-dependent forearm skin microvascular response to acute salt loading in young healthy individuals. Design and method: 16 young healthy men participated in this study (age range 19–24). All subjects took 7-days low-salt (LS) diet – washout period (<3.2 g salt/day) followed by 7-days HS diet (∼14 g salt/day). Skin microvascular blood flow measurement was done using Laser Doppler Flowmetry in response to iontophoresis of acetylcholine (ACh) before and after diet protocols. BP and heart rate (HR) were measured at the beginning of each visit (mean of three repeated measurements). 24h-urine sodium, potassium, urea and creatinine levels were measured before and after diet protocols. Salt intake was estimated based on calculation of 24-hour urinary sodium excretion. Results: Changes in 24 h urinary sodium excretion and calculated salt intake confirmed that subjects conformed to the diet protocols. There was no significant difference in BMI and WHR before and after HS diet. There was no change in BP and HR before and after HS diet. In accordance with our earlier results obtained in young healthy women (flow change compared to basic flow: before HS diet 1797 ± 523 vs. after HS diet 1309 ± 751, P = 0.024; Physiology 2016), ACh induced dilation was significantly impaired after HS diet protocol in young healthy men as well (flow change compared to basic flow: before HS diet 2157 ± 1048 vs. after HS diet 1592 ± 586, P = 0.014). Conclusions: The results of the present study demonstrated that 7-days HS diet impairs forearm skin microvascular ACh-induced dilation independently of BP changes in young healthy men, just as we earlier reported in women. Eventhough there are many known sex-related differences in various cardiovascular responses even in healthy individuals, the results of this study suggesst that one week HS loading affects endothelium-dependent vasodilation in peripheral microcirculation correspondingly in young healthy men and women.

Seven Consecutive Days of Remote Ischemic Preconditioning Improved Cutaneous Vascular Reactivity Induced by Post Occlusive Reactive Hyperemia

ObjectiveRemote ischemic preconditioning (RIPC), induced by brief periods of ischemia followed by reperfusion, elicits strong cardioprotection from ischemia reperfusion injury in animal models. However, recent clinical trials in humans have yielded mixed results that may be explained by coexisting conditions and other experimental factors. Using human skin as an alternative model to study RIPC, we hypothesized that cutaneous vascular reactivity to post‐occlusive reactive hyperemia (PORH) will be increased following repeated RIPC.MethodsYoung healthy participants (26 ± 1 years; 4 male, 5 female) performed RIPC for seven consecutive days. Each daily RIPC session consisted of 4 repetitions of 5 minutes of upper arm blood flow occlusion interspersed by 5 minutes non‐occlusion. Pre‐ and 24 hours post‐RIPC training, an index of skin microvascular blood flow (i.e., cutaneous red blood cell flux) was measured from the ventral forearm using laser speckle contrast imaging. Flux was measured continuously during baseline, 5 minutes of arm blood flow occlusion with 200 mmHg of cuff pressure, and during 5 minutes of PORH. Peak flux during hyperemia, Max (peak after subtracting baseline), Time to peak (Tp) (index of vascular resistance), Max/Tp (indicator of early vascular changes), and area under curve (AUC) were analyzed from collected data. Data are presented as cutaneous vascular conductance (CVC), which was calculated as flux/mean arterial pressure.ResultsSeven consecutive days of RIPC increased Max/Tp (Pre: 0.10 ± 0.02 vs. Post: 0.12 ± 0.02 CVC/sec, p&lt;0.05). Although not statistically different, other indices of PORH were increased; AUC (Pre: 89.7 ± 13.5 vs. Post: 107.2 ± 10.4 CVC·sec, p=0.10), Peak (Pre: 2.18 ± 0.02 vs. Post: 2.28 ± 0.20 CVC, p=0.33), Max (Pre: 1.68 ± 0.20 vs. Post: 1.79 ± 0.20 CVC, p=0.18), and Time to peak (Tp) (Pre: 18.6 ± 1.1 vs. Post: 17.0 ± 1.3 sec, p=0.11).ConclusionsSeven consecutive days of RIPC augmented cutaneous microvascular reactivity to PORH. Collectively, these data support repeated RIPC as a means to improve microvascular function in humans.All experimental procedures were approved by the Institutional Review Board at Des Moines University and conformed to the standards set by the Declaration of Helsinki (IRB#: 08‐15‐05)Support or Funding InformationFunding source: Des Moines University, IOER #03‐14‐01 (PI: J. Lang)This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Impaired Microcirculation in Children After Kidney Transplantation: Everolimus Versus Mycophenolate Based Immunosuppression Regimen

Background/Aims: Whether the immunosuppressive regimen is associated with micro- and macro-vascular status in pediatric kidney transplant recipients (KTx) is unknown. Methods: We performed a cross-sectional, case-control study in 44 pediatric KTx patients on either everolimus (EVR) plus calcineurin inhibitor or standard treatment, i.e. mycophenolate mofetil plus calcineurin inhibitor. Measurement of carotid intima-media thickness (cIMT) via ultrasound, central pulse wave velocity (PWV) by a cuff-based oscillometric technique, and skin microvascular blood flow during local heating via laser-Doppler-fluximetry (LDF) served as marker of subclinical vascular disease. Serum concentrations of angiopoietin-1 and -2, fibroblast-growth factor 23 (FGF23) and soluble klotho were measured. Results: EVR-treated patients exhibited a similar degree of hypertension, increased cIMT, elevated pro-inflammatory angiopoietin-2, and diminished endothelial survival factor angiopoietin-1 compared to healthy children but presented with a twofold more reduced skin micro-vascular function compared to standard treatment (each p< 0.001). By contrast, PWV and soluble klotho levels were normal in both groups. Conclusion: Endothelial dysfunction seems more frequent in KTx patients on EVR-based immunosuppressive regimen compared to standard immunosuppression.

Acute exhaustive rowing exercise reduces skin microvascular dilator function in young adult rowing athletes.

The effect of acute exhaustive exercise session on skin microvascular reactivity was assessed in professional rowers and sedentary subjects. A potential involvement of altered hemodynamic parameters and/or oxidative stress level in the regulation of skin microvascular blood flow by acute exercise were determined. Anthropometric, biochemical, and hemodynamic parameters were measured in 18 young healthy sedentary men and 20 professional rowers who underwent a single acute exercise session. Post-occlusive reactive hyperemia (PORH), endothelium-dependent acetylcholine (ACh), and endothelium-independent sodium nitroprusside (SNP) microvascular responses were assessed by laser Doppler flowmetry in skin microcirculation before and after acute exercise. Serum lipid peroxidation products and plasma antioxidant capacity were measured using spectrophotometry. At baseline, rowers had significantly lower diastolic blood pressure (DBP) and heart rate (HR), and higher stroke volume (SV), PORH, and endothelium-dependent vasodilation than sedentary. Acute exercise caused a significant increase in systolic blood pressure, DBP, HR, and SV and a decrease in total peripheral resistance in both groups. Acute exercise induced a significant impairment in PORH and ACh-induced response in rowers, but not in sedentary, whereas the SNP-induced vasodilation was not affected by acute exercise in any group. Antioxidant capacity significantly increased only in sedentary after acute exercise. Single acute exercise session impaired microvascular reactivity and endothelial function in rowers but not in sedentary, possibly due to (1) more rowing grades and higher exercise intensity achieved by rowers; (2) a higher increase in arterial pressure in rowers than in sedentary men; and (3) a lower antioxidant capacity in rowers.

Impaired neurovascular reactivity in the microvasculature of pregnant women with preeclampsia.

PE is associated with maternal vascular dysfunction, leading to serious cardiovascular risk both during and following pregnancy. To assess microvascular reactivity in pregnant women with PE. A cross-sectional study was performed in 36 pregnant women with PE and 36 normotensive pregnant women (C) in the third trimester. Skin microvascular blood flow was measured using LDF at rest (RF), during the maximum hyperemic response to brief arterial occlusion (MF) and during the sympathetically mediated constrictor response to deep IBH. In pregnant women with PE, RF was higher [C, 8.1 (4.6); PE, 12.0 (7.6), P<.001; PU perfusion units; median (IQR)] and MF/RF [C, 6.1 (3.7); PE, 3. 9 (4.9) P<.001] and peak CVC lower (P=.009) compared to normotensive controls. The constrictor response to IBH [C, 62.4% (27.9); PE, 33.0% (50.6), P=.008] was reduced in women with PE. In univariate analysis, MF/RF was associated with PE status (r=-.417, P=.0001), systolic (r=-.385, P=.001), and diastolic (r=-.388, P=.001) blood pressure, but not BMI (r=.077, P=.536). Women with PE are more than three times more likely to exhibit a reduced microvascular reactivity in the third trimester of pregnancy than normotensive pregnant controls. These differences may be attributable in part to an altered sympathetic neural microvascular tone in PE.

Skeletal Muscle Microvascular-Linked Improvements in Glycemic Control From Resistance Training in Individuals With Type 2 Diabetes.

Insulin increases glucose disposal in part by enhancing microvascular blood flow (MBF) and substrate delivery to myocytes. Insulin's microvascular action is impaired with insulin resistance and type 2 diabetes. Resistance training (RT) improves glycemic control and insulin sensitivity, but whether this improvement is linked to augmented skeletal muscle microvascular responses in type 2 diabetes is unknown. Seventeen (11 male and 6 female; 52 ± 2 years old) sedentary patients with type 2 diabetes underwent 6 weeks of whole-body RT. Before and after RT, participants who fasted overnight had clinical chemistries measured (lipids, glucose, HbA1c, insulin, and advanced glycation end products) and underwent an oral glucose challenge (OGC) (50 g × 2 h). Forearm muscle MBF was assessed by contrast-enhanced ultrasound, skin MBF by laser Doppler flowmetry, and brachial artery flow by Doppler ultrasound at baseline and 60 min post-OGC. A whole-body DEXA scan before and after RT assessed body composition. After RT, muscle MBF response to the OGC increased, while skin microvascular responses were unchanged. These microvascular adaptations were accompanied by improved glycemic control (fasting blood glucose, HbA1c, and glucose area under the curve [AUC] during OGC) and increased lean body mass and reductions in fasting plasma triglyceride, total cholesterol, advanced glycation end products, and total body fat. Changes in muscle MBF response after RT significantly correlated with reductions in fasting blood glucose, HbA1c, and OGC AUC with adjustment for age, sex, % body fat, and % lean mass. RT improves OGC-stimulated muscle MBF and glycemic control concomitantly, suggesting that MBF plays a role in improved glycemic control from RT.