Tissue desaturation is not a major determinant of aging-related impairment in skeletal muscle reactive hyperemia: a retrospective analysis.

Near-infrared spectroscopy combined with vascular occlusion test (NIRS-VOT) is a reactive hyperemia technique for in vivo evaluation of skeletal muscle microvascular reactivity. Previous studies using NIRS-VOT have been shown to be able to detect impairments in microvascular function in high-risk cardiovascular disease populations, such as older individuals. It has been demonstrated that older individuals have slower reactive hyperemia compared with young individuals. Importantly, older individuals also show less desaturation during ischemia compared with young individuals. Based on these findings, it has been suggested that the slower reactive hyperemia observed in older individuals is explained by the lower desaturation during blood flow occlusion (reduced ischemic stimulus). This retrospective analysis compared reactive hyperemia in 36 young and 47 older tissue desaturation-matched individuals that underwent 5-min blood flow occlusion. Overall, we showed that older individuals have impaired reactive hyperemia compared with young when matching for the degree of desaturation and blood flow occlusion time. These findings provide evidence that lower tissue desaturation during ischemia is not a major determinant of impaired reactive hyperemia in older individuals.NEW & NOTEWORTHY Previous findings have suggested that aging-related impairment in skeletal muscle reactive hyperemia is majorly influenced by a lower degree of tissue desaturation during ischemia in older individuals compared with young individuals. In a retrospective analysis including 83 tissue desaturation-matched individuals, we show that the degree of tissue desaturation is not a major determinant of aging-related impairments in reactive hyperemia.

Reactive Hyperemia and Cardiovascular Autonomic Neuropathy in Type 2 Diabetic Patients: A Systematic Review of Randomized and Nonrandomized Clinical Trials.

Objective: This work aimed to determine the relationship between the autonomic nervous system and reactive hyperemia (RH) in type 2 diabetes patients with and without cardiovascular autonomic neuropathy (CAN). Methodology: A systematic review of randomized and nonrandomized clinical studies characterizing reactive hyperemia and autonomic activity in type 2 diabetes patients with and without CAN was performed. Results: Five articles showed differences in RH between healthy subjects and diabetic patients with and/or without neuropathy, while one study did not show such differences between healthy subjects and diabetic patients, but patients with diabetic ulcers had lower RH index values compared to healthy controls. Another study found no significant difference in blood flow after a muscle strain that induced reactive hyperemia between normal subjects and non-smoking diabetic patients. Four studies measured reactive hyperemia using peripheral arterial tonometry (PAT); only two found a significantly lower endothelial-function-derived measure of PAT in diabetic patients than in those without CAN. Four studies measured reactive hyperemia using flow-mediated dilation (FMD), but no significant differences were reported between diabetic patients with and without CAN. Two studies measured RH using laser Doppler techniques; one of them found significant differences in the blood flow of calf skin after stretching between diabetic non-smokers and smokers. The diabetic smokers had neurogenic activity at baseline that was significantly lower than that of the normal subjects. The greatest evidence revealed that the differences in RH between diabetic patients with and without CAN may depend on both the method used to measure hyperemia and that applied for the ANS examination as well as the type of autonomic deficit present in the patients. Conclusions: In diabetic patients, there is a deterioration in the vasodilator response to the reactive hyperemia maneuver compared to healthy subjects, which depends in part on endothelial and autonomic dysfunction. Blood flow alterations in diabetic patients during RH are mainly mediated by sympathetic dysfunction. The greatest evidence suggests a relationship between ANS and RH; however, there are no significant differences in RH between diabetic patients with and without CAN, as measured using FMD. When the flow of the microvascular territory is measured, the differences between diabetics with and without CAN become evident. Therefore, RH measured using PAT may reflect diabetic neuropathic changes with greater sensitivity compared to FMD.

Association between Femoral Artery Flow-Mediated Dilation and Muscle Oxygen Saturation Parameters in Healthy, Young Individuals.

Flow-mediated dilation (FMD) and muscle oxygen saturation (StO2) are measurements utilized to assess macro- and microvascular function, respectively. Macro- and microvascular dysfunction may occur differently depending on the clinical condition. Since microvascular responsiveness can influence upstream conduit artery hemodynamics, the present study aimed to investigate whether a correlation between FMD and muscle StO2 parameters exists. Sixteen healthy, young individuals were enrolled in this study. Femoral artery FMD and tibial anterior muscle StO2 were evaluated by ultrasound and near-infrared spectroscopy, respectively. The FMD and muscle StO2 parameters were assessed by employing a vascular occlusion test (VOT). The oxygen resaturation rate was determined by calculating the upslope of StO2 immediately after occlusion and the magnitude of reperfusion as the difference between the highest and lowest StO2 value achieved during the reperfusion phase. The oxygen desaturation rate and the magnitude of desaturation during the VOT were also evaluated. A significant correlation between the FMD and oxygen resaturation rate (r = 0.628; p = 0.009), magnitude of reperfusion (r = 0.568; p = 0.022), oxygen desaturation rate (r = -0.509; p = 0.044), and magnitude of desaturation (r = 0.644; p = 0.007) was observed. This study demonstrated a moderate association between the femoral artery FMD and tibial anterior StO2 parameters in young individuals.

The effect of dietary nitrate on macro- and microvascular function: A systematic review.

Previous studies have investigated the impact of dietary nitrate on vascular function due to the association between dietary nitrate ingestion and improvement in nitric oxide (NO) bioavailability. Considering that NO can present different effects through vascular beds (macro- vs. microvasculature) due to the specific characteristic (function and morphology) that each vessel exhibits, it is crucial to investigate the effect of dietary nitrate ingestion on the macro- and microvascular function to understand the effect of nitrate on vascular function. For this reason, this review aimed to evaluate the impact of dietary nitrate on macro- and microvascular function in humans. A total of 29 studies were included in the systematic review, of which 19 studies evaluated the effect of nitrate supplementation on macrovascular function, eight studies evaluated the effect on microvascular function, and two studies evaluated the impact on both macro- and microvascular function. The literature suggests that dietary nitrate ingestion seems to improve the vascular function in macrovasculature, whereas microvascular function appears to be modest. Future studies investigating the effect of nitrate ingestion on vascular function should focus on measuring macro- and microvascular function whenever possible so that the impact of nitrate-rich foods on vascular segments could be better understood.

Effects of aerobic, resistance, and combined training on endothelial function and arterial stiffness in older adults: study protocol for a systematic review and meta-analysis.

INTRODUCTION: Aging is an independent risk factor for cardiovascular events. It promotes vascular dysfunction which is associated with risk factors for cardiovascular diseases (CVDs). Exercise can modulate vascular function parameters, but little is known about the effects of different modalities of training (aerobic, resistance, and combined) on endothelial function and arterial stiffness in older adults. METHODS: This systematic review study will include randomized controlled trials (RCTs) selected from the electronic databases MEDLINE (PubMed), Cochrane, LILACS, EMBASE, and Web of Science. We will follow the PRISMA guidelines and PICOS framework. Studies involving both male and female older adults (≥60 years old) with or without comorbidities undergoing aerobic, resistance, and/or combined training compared to a control group (no exercise) will be eligible. We will use the Cochrane Risk of Bias 2 (RoB 2) tool to evaluate the quality of individual studies and GRADE to assess the strength of evidence. Statistical analyses will be conducted with RStudio for Windows (v1.3.959) using R package meta. DISCUSSION: A systematic review and meta-analysis involving data from studies of older adults would deepen our understanding of vascular adaptations to exercise training in this population. It could provide new insights into how health providers can improve patient management and prevention of cardiovascular events in older adults. SYSTEMATIC REVIEW REGISTRATION: PROSPERO 42021275451.

Effects of dietary supplementation with creatine on homocysteinemia and systemic microvascular endothelial function in individuals adhering to vegan diets.

The incidence of cardiovascular diseases in vegetarian individuals is lower than that in the general population. Nevertheless, individuals who adhere to vegan diets have a higher prevalence of hyperhomocysteinemia with eventual adverse effects on vascular reactivity. Creatine supplementation (CrS) reduces plasma homocysteine levels and enhances vascular reactivity in the microcirculation. Thus, we investigated the effects of CrS on systemic microcirculation and homocysteine blood levels in strict vegan subjects. Forty-nine strict vegan subjects were allocated to the oral CrS (5 g micronized creatine monohydrate daily for three weeks; n = 31) and placebo (n = 18) groups. Laser speckle contrast imaging coupled with acetylcholine skin iontophoresis was used to evaluate cutaneous microvascular reactivity, and intravital video-microscopy was used to evaluate skin capillary density and reactivity before and after CrS. We demonstrated that CrS reduces the plasma levels of homocysteine and increases those of folic acid. After the CrS period, the homocysteine levels of all of the vegan subjects normalized. CrS also induced increases in baseline skin functional capillary density and endothelium-dependent capillary recruitment in both normo- (N-Hcy) and hyperhomocysteinemic (H-Hcy) individuals. CrS increased endothelium-dependent skin microvascular vasodilation in the H-Hcy vegan subjects but not in the N-Hcy vegan subjects. In conclusion, three weeks of oral CrS was sufficient to increase skin capillary density and recruitment and endothelium-dependent microvascular reactivity. CrS also resulted in plasma increases in folic acid levels and reductions in homocysteine levels among only the H-Hcy individuals.

Vascular function in asthmatic children and adolescents.

BACKGROUND: Epidemiological studies have demonstrated an increased incidence of cardiovascular events in patients with bronchial asthma, but little is known about the relationship between asthma and vascular function. The purpose of this study was to evaluate endothelial function and arterial stiffness in children and adolescents with asthma. METHODS: A cross-sectional controlled study was designed. Measurements of endothelial function and arterial stiffness in asthmatic (13.6 ± 0.6 years) and control groups (14.9 ± 0.7 years) were taken by the non-invasive peripheral arterial tonometry (EndoPAT2000) determined by using the natural logarithm of the reactive hyperemia index (LnRHI) and the augmentation index (AIx@75%), respectively. Patients with asthma were also administered two questionnaires to evaluate asthma control and quality of life. Exercise functional capacity was evaluated using the Shuttle Walking Test (SWT). Only male participants were included in the present study. RESULTS: LnRHI and the walked distance during the SWT were similar between groups (p = 0.23 and p = 0.50, respectively). AIx@75% was significantly higher in the asthmatic group (-7.75 ± 1.7) compared to the control group (-15.25 ± 1.8), p < 0.04. In the control group, the LnRHI correlated positively with baseline systolic blood pressure (r = 0.53, p = 0.02) and mean arterial pressure (r = 0.50, p = 0.03), age (r = 0.61, p = 0.007), weight (r = 0.63, p = 0.004) and height (r = 0.56, p = 0.015). Besides that LnRHI correlated with FVC (r = 0.69, p = 0.002), FEV1, (r = 0.53, p = 0.03) and negatively with Tiffeneau index (FEV1/FVC%, r = -0.49 p = 0.04). The LnRHI of the asthmatic group did not correlate with the different variables evaluated. CONCLUSION: The increased AIx@75% without changes in LnRHI in asthmatic patients could mean that an early detection of vascular impairment may precede endothelial dysfunction, and that different mechanisms may contribute to the pathogenesis and progression of cardiovascular events in this population. A large prospective and randomized controlled study should be done to evaluate the physiopathological mechanisms underlying the association between arterial stiffness and asthma.

A novel effective method for the assessment of microvascular function in male patients with coronary artery disease: a pilot study using laser speckle contrast imaging

Evaluation of microvascular endothelial function is essential for investigating the pathophysiology and treatment of cardiovascular and metabolic diseases. Although laser speckle contrast imaging technology is well accepted as a noninvasive methodology for assessing microvascular endothelial function, it has never been used to compare male patients with coronary artery disease with male age-matched healthy controls. Thus, the aim of this study was to determine whether laser speckle contrast imaging could be used to detect differences in the systemic microvascular functions of patients with established cardiovascular disease (n=61) and healthy age-matched subjects (n=24). Cutaneous blood flow was assessed in the skin of the forearm using laser speckle contrast imaging coupled with the transdermal iontophoretic delivery of acetylcholine and post-occlusive reactive hyperemia. The maximum increase in skin blood flow induced by acetylcholine was significantly reduced in the cardiovascular disease patients compared with the control subjects (74 vs 116%; P<0.01). With regard to post-occlusive reactive hyperemia-induced vasodilation, the patients also presented reduced responses compared to the controls (0.42±0.15 vs 0.50±0.13 APU/mmHg; P=0.04). In conclusion, laser speckle contrast imaging can identify endothelial and microvascular dysfunctions in male individuals with cardiovascular disease. Thus, this technology appears to be an efficient non-invasive technique for evaluating systemic microvascular and endothelial functions, which could be valuable as a peripheral marker of atherothrombotic diseases in men.

Alteraciones vasculares en ancianos de un área de salud de Santiago de Cuba / Vascular diseases in old men of a health area in Santiago de Cuba

Se realizó un estudio descriptivo y transversal de 65 ancianos pertenecientes al área de salud del Policlínico Docente "Armando García Aspurú" de Santiago de Cuba, de enero a mayo del 2012, con vistas a determinar las alteraciones vasculares en ellos mediante la prueba de la hiperemia reactiva con el fotopletismógrafo digital Angiodin. La asociación estadística entre las variables clínicas se estableció por la prueba de la Χ², con una significación menor de 0,05. Entre los resultados relevantes figuraron el grupo etario de 60 a 69 años (49,2 %) y el sexo femenino (72,3 %). Asimismo, la macroangiopatía predominó en 80,0 % de los ancianos, y no se mostró dependiente de la edad, aunque sí se mostró dependiente del sexo, donde los hombres fueron los más afectados. El factor de riesgo más frecuente fue la hipercolesterolemia, que fue dependiente de la prueba realizada, seguido del antecedente familiar de diabetes mellitus.

A descriptive and cross-sectional study of 65 old men, belonging to the health area of "Armando García Aspurú" Teaching Polyclinic in Santiago de Cuba, was carried from January to May, 2012, with the aim of determining the vascular diseases in them by means of the reactive hyperemia test made with the digital photoplethysmograph Angiodin® PD 3000. The statistical association among the clinical variables was settled down through the chi-squared test, with a significance lower than 0.05. Among the outstanding results there were the 60-69 years age group (49.2%) and the female sex (72.3%). Also, the macroangiopathy prevailed in 80.0% of old men, with no dependence on the age, although it was dependent on the sex, where men were the most affected ones. The more frequent risk factor was hypercholesterolemia that was dependent on the carried out test, followed by the familiar history of diabetes mellitus.

Tratamiento antihipertensivo diurno y nocturno: efecto en la función endotelial de pacientes con patrón non-dipper / Day and night antihypertensive treatment: effect on endothelial function in patients with non-dipper pattern

Analizar el efecto del tratamiento antihipertensivo diurno y nocturno sobre la función endotelial en pacientes con patrón non-dipper identificados en la consulta de la Unidad Cardiometabólica del Departamento de Medicina Interna del Hospital Militar Dr. Carlos Arvelo durante el segundo cuatrimestre (Mayo – Agosto) del año 2012. Se realizó un estudio abierto, prospectivo, descriptivo y analítico durante un período de 8 semanas comparando la respuesta de la hiperemia reactiva y microalbuminuria con el horario de administración del tratamiento antihipertensivo, independientemente del tipo y número de drogas utilizadas. La muestra fue constituida por pacientes hipertensos con patrón non-dippersin otras comorbilidades que fueron diagnosticados en la Unidad Cardiometabólica del Hospital Militar Dr. Carlos Arvelo durante el segundo cuatrimestre del año 2012. La media de edades fue 57,84 ± 5,01DE para el grupo diurno y 55,07 ± 3,77DE para el grupo nocturno. Predominó el sexo femenino 69,23% y 92,3% respectivamente. Se observó mayor caída sistólica y mayor cambio de patrón non-dipper a dipper en el grupo con tratamiento nocturno que en aquel con tratamiento diurno (p=0,016 y p=0,011 respectivamente). No se observaron diferencias significativas con el resto de las variables. Se demostró una relación estadísticamente significativa entre la administración nocturna del tratamiento antihipertensivo y la caída nocturna de presión sistólica, condicionando el cambio del patrón non-dipper a dipper.

To analyze the effect of diurnal and nocturnal anti-hypertensive treatment on endothelial function in patients with a non-dipper pattern identified at the Cardio-metabolic Unit of the Internal Medicine Department, Military Hospital Dr. Carlos Arvelo, Caracas, Venezuela during the second quarter (May – August) of 2012. An open-label, prospective, descriptive and analytical study, was conducted over a period of 8 weeks comparing the reactive hyperemia and microalbuminuria to the schedule of administration of the anti-hypertensive treatment, regardless of the type and number of drugs used. The sample was composed of hypertensive patients with a non-dipper pattern without other comorbidities who consulted at the Cardiometabolic Unit of the Internal Medicine Department at the Military Hospital Dr. Carlos Arvelo during the second quarter of 2012. The average age was 57.84 ± 5.01SD for the day-time group and 55.07 ± 3.77SD for the nocturnal group. Females were predominant over males with 69.23% and 92.3% respectively. There was a greater systolic drop and a greater change from non-dipperto a dipper pattern in the group receiving nocturnal treatment than in the diurnal group (p=0.016 and p=0.011 respectively). No significant differences were observed in the rest of the variables. There was a statistically significant relationship between the nocturnal administration of anti-hypertensive treatment and the night systolic pressure drop, conditioning a change from non-dipper to a dipper pattern.