Sensitivity of the Vasoactive Range in Determining Aerobic Fitness

Previous work has demonstrated a direct relationship between aerobic fitness and indices of vasodilatory function (i.e., Flow-mediated Dilation; FMD). Importantly, recent evidence suggests that vasoconstrictor function to reductions in blood flow (i.e., Low-Flow Mediated Constriction; L-FMC), as well as during sympatho-excitation (i.e., Cold Pressor Test), may compliment the FMD measure, thus, providing an overall range of vascular responsiveness. The purpose of this thesis project was to test the hypothesis that vasoactive range indices (peak vasodilation + nadir vasoconstriction) are sensitive to aerobic fitness levels in healthy young men. Fourteen males (age: 22±4 yrs) were recruited, and divided evenly into a high (HF) vs. low (LF) aerobic fitness group, quantified via YMCA cycle ergometry (VO2 peak extrapolation), and a 3-min step test (1-min HR recovery). Duplex Doppler-ultrasound was used to assess brachial artery responses to the following physiological stimuli: FMD, L-FMC, CPT, and local heating. Vasodilatory responses were calculated from the peak change in artery diameter, and vasoconstrictor responses were determined from the nadir values in response to stimuli, respectively. VO2 peak (HF=55±10 vs. LF=38±6) and HR recovery (HF=38±12 vs. LF=24±9 beats) were greater in the HF group (P\u3c0.05). All vasoactive range indices were similar between groups; however, L-FMC change tended to be greater in HF (HF=0.1±0.06 vs. LF=0.02±0.07mm, P=0.057). A correlational analysis revealed an inverse relationship between L-FMC and HR recovery (r=-0.653, P=0.02). Collectively, these findings suggests that vasoactive range indices are not sensitive to aerobic fitness in healthy young men; however, high fit individuals may exhibit greater vasoconstrictor function to reductions in blood flow

Conduit artery structure and function in lowlanders and native highlanders: relationships with oxidative stress and role of sympathoexcitation

Research detailing the normal vascular adaptions to high altitude is minimal and often confounded by pathology (e.g. chronic mountain sickness) and methodological issues. We examined vascular function and structure in: (1) healthy lowlanders during acute hypoxia and prolonged ( 2 weeks) exposure to high altitude, and (2) high-altitude natives at 5050 m (highlanders). In 12 healthy lowlanders (aged 32 ± 7 years) and 12 highlanders(Sherpa; 33 ± 14 years) we assessed brachial endothelium-dependent flow-mediated dilatation(FMD), endothelium-independent dilatation (via glyceryl trinitrate; GTN), common carotid intima–media thickness (CIMT) and diameter (ultrasound), and arterial stiffness via pulse wave velocity (PWV; applanation tonometry). Cephalic venous biomarkers of free radical-mediated lipid peroxidation (lipid hydroperoxides, LOOH), nitrite (NO2 –) and lipid soluble antioxidants were also obtained at rest. In lowlanders, measurements were performed at sea level (334 m) and between days 3–4 (acute high altitude) and 12–14 (chronic high altitude) following arrival to 5050 m. Highlanders were assessed once at 5050 m. Compared with sea level, acute high altitude reduced lowlanders’ FMD (7.9 ± 0.4 vs. 6.8 ± 0.4%; P = 0.004) and GTN-induced dilatation (16.6 ± 0.9 vs. 14.5 ± 0.8%; P = 0.006), and raised central PWV (6.0 ± 0.2 vs. 6.6 ± 0.3 m s−1; P = 0.001). These changes persisted at days 12–14, and after allometricallyscaling FMD to adjust for altered baseline diameter. Compared to lowlanders at sea level and high altitude, highlanders had a lower carotid wall:lumen ratio ( 19%, P 0.04), attributable to a narrower CIMT and wider lumen. Although both LOOH and NO2 – increased with high altitude in lowlanders, only LOOH correlated with the reduction in GTN-induced dilatation evident during acute (n = 11, r=−0.53) and chronic (n = 7, r=−0.69; P 0.01) exposure to 5050 m. In a follow-up, placebo-controlled experiment (n=11 healthy lowlanders) conducted in a normobaric hypoxic chamber (inspiredO2 fraction (FIO2 )=0.11; 6 h), a sustained reduction in FMD was evident within 1 h of hypoxic exposure when compared to normoxic baseline (5.7±1.6 vs. 8.0 ±1.3%; P < 0.01); this decline in FMD was largely reversed following α1-adrenoreceptor blockade. In conclusion, high-altitude exposure in lowlanders caused persistent impairment in vascular function, which was mediated partially via oxidative stress and sympathoexcitation. Although a lifetime of high-altitude exposure neither intensifies nor attenuates the impairments seen with short-term exposure, chronic high-altitude exposure appears to be associated with arterial remodelling

A Methodological Approach to Non-invasive Assessments of Vascular Function and Morphology

The endothelium is the innermost lining of the vasculature and is involved in the maintenance of vascular homeostasis. Damage to the endothelium may predispose the vessel to atherosclerosis and increase the risk for cardiovascular disease. Assessments of peripheral endothelial function are good indicators of early abnormalities in the vascular wall and correlate well with assessments of coronary endothelial function. The present manuscript details the important methodological steps necessary for the assessment of microvascular endothelial function using laser Doppler imaging with iontophoresis, large vessel endothelial function using flow-mediated dilatation, and carotid atherosclerosis using carotid artery ultrasound. A discussion on the methodological considerations for each of the techniques is also presented, and recommendations are made for future research

Endothelial function assessment in atherosclerosis: Comparison of brachial artery flow‑mediated vasodilation and peripheral arterial tonometry

INTRODUCTION Endothelial dysfunction, characterized by the loss of nitric oxide bioavailability, is a key element in the pathogenesis of atherosclerosis and an important prognostic factor in cardiovascular diseases. Therefore, the development of reliable, safe, and noninvasive methods of endothelial function assessment is important for their use in cardiovascular risk stratification. Brachial artery flow‑mediated dilation (FMD) is widely used in research but technical difficulties and problems with calibration between laboratories limit its clinical use. Reactive hyperemia–peripheral artery tonometry (RH‑PAT, EndoPAT) has been developed as a simpler, cheaper, and potentially more reproducible method. OBJECTIVES We aimed to investigate associations between RH‑PAT and FMD in relation to atherosclerotic risk factor profile. PATIENTS AND METHODS The study involved 80 subjects (52 men, 28 women) aged 43.6 ±14.8 years, with moderate‑to‑low cardiovascular risk (mean SCORE, 2.2% ±2%), in whom FMD, RH‑PAT, and intima–media thickness (IMT) were determined. RESULTS The reactive hyperemia index (RHI) measured by RH‑PAT correlated with FMD (r = 0.35, P &lt;0.01). However, no significant correlation was observed between RHI and IMT, SCORE, or the number of classical atherosclerotic risk factors (hypertension, smoking, diabetes, hypercholesterolemia), while FMD was significantly correlated with IMT (r = –0.53, P &lt;0.001), risk factors (r = –0.55, P &lt;0.05), and SCORE (r = –0.4, P &lt;0.05). CONCLUSIONS Despite its technical requirements, FMD is a more sensitive method than RH‑PAT in evaluating the effect of classical atherosclerotic risk factors on vascular endothelial function. Microvasculature response during RH‑PAT needs to be further studied, including the assessment of nonendothelial factors that may affect the measurements, before RH‑PAT becomes the universal tool for the evaluation of the endothelial cells

Wine Dilates the Brachial Artery but does not Increase Flow-mediated Dilatation over Two Hours

Epidemiological evidence suggests cardiovascular benefits from the consumption of alcoholic beverages, butcorroboration by functional and outcome studies is still outstanding. Non-invasive functional tests on the brachialarteries of healthy volunteers were performed before and for two hours after consuming red wine. Brachial arterydimensions were determined by ultrasound at baseline, 30, 60 and 120 min. Flow-mediated dilatation (FMD) wassimilarly assessed. Putative minimum and maximum lumen diameters were determined after ice immersion andsublingual trinitroglycerine (TNG) at baseline and 60 min after wine consumption. Sixteen subjects had a meanresting brachial artery diameter of 3.84 mm, which significantly increased with wine to 4.44 mm at 30 min, 4.39mm at 60 min and 4.49 mm at 120 min. The calculated blood flow rates during the study did not differ significantlyover the measured intervals. The baseline mean diameter with TNG was not significantly different from the dilationwith wine. The vasoconstrictor response varied, with a -2.6 ± 2.9% change with wine, compared with the baselinediameter. There was appreciable variation of the diameter relative to the range found with ice and TNG. Thecalculated FMDs (% changes) for the study were 10.8, 6.1, 5.6 and 7.5, indicating statistically significant effects ofwine (p &lt; 0.0001). The authors conclude that red wine consumption leads to beneficial arterial effects that mayrelate to different doses or other mechanisms than FMD. Further studies need to be done to discriminate betweenthe effects of alcohol and phenolic compounds on vascular function

Reliability of flow-mediated dilation measures in the popliteal artery and implications for use in clinical and research practices

PURPOSE: The aim of the present study was to assess the internal consistency and stability reliability of flow-mediated dilation (FMD) in the popliteal artery and to investigate the effect of occlusion pressure on the FMD response. METHODS: A series of FMD tests were performed on ten healthy young adult males to assess reliability. Ultrasound-derived artery diameter of the popliteal was measured and FMD was calculated as the percent change in diameter from baseline. RESULTS: FMD measurements for intra- and interday comparisons demonstrated poor reliability (Repeatability 5.62 and 4.82%, Intraclass correlation coefficient [ICC] 0.36 and 0.25, respectively). Repeatability values were as large as the FMD measures themselves for both intra- and interday reliability. CONCLUSION: Popliteal artery FMD has poor reliability for internal consistency and stability reliability. Interpretation of individual or group changes using this technique should be interpreted with caution

The Markers of Endothelial Activation

Biomarkers are biological indicators of processes that are part of ethiopathogenesis of the diseases, and can, but do not have to be causal to diseases. One very important question is how specific and sensitive the marker is, since one molecule can appear in many conditions. Biomarkers of endothelial cell activation can be very diverse, from biochemical/metabolic to functional biomarkers. Activation of endothelial cells is part of physiological as well as pathophysiological response of cardiovascular system in conditions as physical activity, growth, pregnancy and in all cardiometabolic diseases (e.g., hypertension, diabetes mellitus, autoimmune inflammatory diseases, coronary artery disease, atherosclerosis, ischemia and reperfusion, etc.). During activation, there is a change in endothelial cell morphology and function, which could be a defensive response of endothelium to provoking factor or could lead to increased risk for the injury and end organ damage. This chapter aims to overview current knowledge on established biomarkers of normal and disease-related endothelial activation and to provide information on novel, potential biomarkers in common cardiometabolic diseases

Noninvasive Assessment of Preclinical Atherosclerosis

Initially considered as a semipermeable barrier separating lumen from vessel wall, the endothelium is now recognised as a complex endocrine organ responsible for a variety of physiological processes vital for vascular homeostasis. These include the regulation of vascular tone, luminal diameter, and blood flow; hemostasis and thrombolysis; platelet and leucocyte vessel-wall interactions; the regulation of vascular permeability; and tissue growth and remodelling. The endothelium modulates arterial stiffness, which precedes overt atherosclerosis and is an independent predictor of cardiovascular events. Unsurprisingly, dysfunction of the endothelium may be considered as an early and potentially reversible step in the process of atherogenesis and numerous methods have been developed to assess endothelial status and large artery stiffness. Methodology includes flow-mediated dilatation of the brachial artery, assessment of coronary flow reserve, carotid intimamedia thickness, pulse wave analysis, pulse wave velocity, and plethysmography. This review outlines the various modalities, indications, and limitations of available methods to assess arterial dysfunction and vascular risk