scholarly journals GLP-1 at physiological concentrations recruits skeletal and cardiac muscle microvasculature in healthy humans

2014 ◽  
Vol 127 (3) ◽  
pp. 163-170 ◽  
Author(s):  
Sharmila C. Subaran ◽  
Matthew A. Sauder ◽  
Weidong Chai ◽  
Linda A. Jahn ◽  
Dale E. Fowler ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cardiac Muscle ◽  
Brachial Artery ◽  
Microvascular Perfusion ◽  
Brachial Artery Diameter ◽  
Healthy Humans

GLP-1 increases microvascular perfusion in both skeletal and cardiac muscle, and brachial artery diameter and blood flow in humans. These vascular actions may contribute to the beneficial actions of the GLP-1 receptor analogues.

scholarly journals GLP-1 and Insulin Recruit Muscle Microvasculature and Dilate Conduit Artery Individually But Not Additively in Healthy Humans

2018 ◽  
Vol 2 (2) ◽  
pp. 190-206 ◽  
Author(s):  
Alvin W K Tan ◽  
Sharmila C Subaran ◽  
Matthew A Sauder ◽  
Weidong Chai ◽  
Linda A Jahn ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cardiac Muscle ◽  
Flow Velocity ◽  
Surface Area ◽  
Brachial Artery ◽  
Microvascular Perfusion ◽  
Brachial Artery Diameter ◽  
Nutrient Delivery ◽  
Conduit Artery ◽  
Endothelial Surface

Abstract Context Glucagon-like peptide-1 (GLP-1) and insulin increase muscle microvascular perfusion, thereby increasing tissue endothelial surface area and nutrient delivery. Objective To examine whether GLP-1 and insulin act additively on skeletal and cardiac microvasculature and conduit artery. Design Healthy adults underwent three study protocols in random order. Setting Clinical Research Unit at the University of Virginia. Methods Overnight-fasted participants received an intravenous infusion of GLP-1 (1.2 pmol/kg/min) or normal saline for 150 minutes with or without a 2-hour euglycemic insulin clamp (1 mU/kg/min) superimposed from 30 minutes onward. Skeletal and cardiac muscle microvascular blood volume (MBV), flow velocity, and flow; brachial artery diameter, flow velocity, and blood flow; and pulse wave velocity (PWV) were measured. Results GLP-1 significantly increased skeletal and cardiac muscle MBV and microvascular blood flow (MBF) after 30 minutes; these remained elevated at 150 minutes. Insulin also increased skeletal and cardiac muscle MBV and MBF. Addition of insulin to GLP-1 did not further increase skeletal and cardiac muscle MBV and MBF. GLP-1 and insulin increased brachial artery diameter and blood flow, but this effect was not additive. Neither GLP-1, insulin, nor GLP-1 and insulin altered PWV. Combined GLP-1 and insulin infusion did not result in higher whole-body glucose disposal. Conclusion GLP-1 and insulin at physiological concentrations acutely increase skeletal and cardiac muscle microvascular perfusion and dilate conduit artery in healthy adults; these effects are not additive. Thus, GLP-1 and insulin may regulate skeletal and cardiac muscle endothelial surface area and nutrient delivery under physiological conditions.

scholarly journals Insulin at physiological concentrations increases microvascular perfusion in human myocardium

2007 ◽  
Vol 293 (5) ◽  
pp. E1250-E1255 ◽  
Author(s):  
Zhenqi Liu
Keyword(s):  
Blood Flow ◽  
Flow Velocity ◽  
Brachial Artery ◽  
Contrast Echocardiography ◽  
Human Myocardium ◽  
Microvascular Perfusion ◽  
Microvascular Blood Flow ◽  
Brachial Artery Diameter ◽  
Healthy Humans ◽  
Meal Feeding

Vascular endothelium regulates vascular tone and tissue perfusion in response to various physiological and pathological stimuli. Insulin and meal feeding increase microvascular perfusion and thus oxygen, nutrient, and hormone delivery to human skeletal muscle. Meal feeding also increases cardiac microvascular perfusion in healthy humans. To examine whether insulin at physiological concentrations increases microvascular perfusion in human myocardium, we studied 13 healthy, overnight-fasted, lean, young human volunteers by using myocardial contrast echocardiography (MCE) and insulin-clamp techniques. We measured cardiac microvascular blood volume (MBV), microvascular flow velocity (MFV), and microvascular blood flow (MBF) at baseline, 60 min, and 120 min after initiating insulin infusion at 1 mU·kg−1·min−1. MBF is the product of MBV and MFV and represents microvascular perfusion. Insulin increased myocardial MBV by 23% at 60 min ( P < 0.01) and by 41% at 120 min ( P = 0.001) without changing MFV. As a result, insulin-mediated myocardial MBF increased significantly at both 60 min ( P < 0.01) and 120 min ( P < 0.0005). Insulin also significantly increased brachial artery diameter, flow velocity, and total blood flow at 60 and 120 min ( P < 0.05 for all). The changes in cardiac MBV correlated positively with quantitative insulin sensitivity check index (QUICKI) and negatively with body mass index but not with the steady-state glucose-infusion rates or the changes in brachial artery parameters. We conclude that insulin, at physiologically relevant concentrations, increases microvascular perfusion in human heart muscle by increasing cardiac MBV in healthy, insulin-sensitive adults. This insulin-mediated cardiac microvascular perfusion may play an important role in normal human myocardial oxygen and substrate physiology.

scholarly journals Measuring peripheral resistance and conduit arterial structure in humans using Doppler ultrasound

2005 ◽  
Vol 98 (6) ◽  
pp. 2311-2315 ◽  
Author(s):  
Louise H. Naylor ◽  
Cara J. Weisbrod ◽  
Gerry O'Driscoll ◽  
Daniel J. Green
Keyword(s):  
Blood Flow ◽  
Brachial Artery ◽  
Peripheral Resistance ◽  
Artery Blood Flow ◽  
Brachial Artery Diameter ◽  
Resistance Vessel ◽  
Conduit Artery ◽  
Significant Difference ◽  
Vessel Structure

The purpose of this study was to establish valid indexes of conduit and resistance vessel structure in humans by using edge detection and wall tracking of high-resolution B-mode arterial ultrasound images, combined with synchronized Doppler waveform envelope analysis, to calculate conduit artery blood flow and diameter continuously across the cardiac cycle. Nine subjects aged 36.7 (9.2) yr underwent, on separate days, assessment of brachial artery blood flow and diameter response to 5-, 10-, and 15-min periods of forearm ischemia in the presence and absence of combined sublingual glyceryl trinitrate (GTN) administration. Two further sessions examined responses to ischemic exercise, one in combination with GTN. The peak brachial artery diameter was observed in response to the combination of ischemic exercise and GTN; a significant difference existed between resting brachial artery diameter and peak brachial artery diameter, indicating that resting diameter may be a poor measure of conduit vessel structure in vivo. Peak brachial artery flow was also observed in response to a combination of forearm ischemia exercise and GTN administration, the response being greater than that induced by periods of ischemia, GTN, or ischemic exercise alone. These data indicate that noninvasive indexes of conduit and resistance vessel structure can be simultaneously determined in vivo in response to a single, brief, stimulus and that caution should be applied in using resting arterial diameter as a surrogate measure of conduit artery structure in vivo.

scholarly journals Brachial artery diameter, blood flow and flow-mediated dilation in sleep-disordered breathing

2009 ◽  
Vol 14 (4) ◽  
pp. 351-360 ◽  
Author(s):  
Hassan A Chami ◽  
Michelle J Keyes ◽  
Joseph A Vita ◽  
Gary F Mitchell ◽  
Martin G Larson ◽  
...  
Keyword(s):  
Blood Flow ◽  
Brachial Artery ◽  
Sleep Disordered Breathing ◽  
Flow Mediated Dilation ◽  
Brachial Artery Diameter ◽  
Disordered Breathing

Occlusion cuff position is an important determinant of the time course and magnitude of human brachial artery flow-mediated dilation

2000 ◽  
Vol 99 (4) ◽  
pp. 261-267 ◽  
Author(s):  
Karen L. BERRY ◽  
R. Andrew P. SKYRME-JONES ◽  
Ian T. MEREDITH
Keyword(s):  
Blood Flow ◽  
Brachial Artery ◽  
Time Course ◽  
Arterial Occlusion ◽  
Flow Mediated Dilation ◽  
Reactive Hyperaemia ◽  
Upper Arm ◽  
Brachial Artery Diameter ◽  
Occlusion Cuff ◽  
Forearm Occlusion

Non-invasive ultrasound techniques to assess flow-mediated vasodilation (FMD) are frequently used to assess arterial endothelial vasodilator function. However, the range of normal values varies considerably, possibly due to differences in methodological factors. We sought to determine the effect of occlusion cuff position on the time course and magnitude of brachial artery blood flow and flow-mediated dilation. Twelve healthy subjects underwent measurements of forearm blood flow using venous occlusion plethysmography (VOP) before and after 5 min of susprasystolic cuff inflation, using two randomly assigned occlusion cuff positions (upper arm and forearm). An additional 16 subjects underwent two brachial ultrasound studies, using the two cuff positions, to assess the extent and time course of changes in brachial artery diameter and blood flow. Maximum increase in blood flow (peak reactive hyperaemia), measured by VOP, occurred immediately upon each cuff deflation, but was greater after upper arm compared with forearm arterial occlusion (33.1±3.1 versus 22.8±2.2 ml/min per forearm tissue, P = 0.001). Maximal brachial artery FMD was significantly greater following upper arm occlusion (9.0±1.2%, mean±S.E.M.) compared with forearm occlusion (5.9±0.7%, P = 0.01). The time course of the change in brachial artery diameter was affected differently in response to each protocol. The time to peak dilation following upper arm occlusion was delayed by 22 s compared with forearm occlusion. Occlusion cuff position is thus a powerful determinant of peak reactive hyperaemia, volume repaid and the extent and time course of brachial artery FMD. Positioning the cuff on the upper arm produces a greater FMD. These results highlight the need for comparisons between FMD studies to be made with care.

scholarly journals Noninvasive Assessment of Endothelium-Dependent Flow-Mediated Dilation of the Brachial Artery

1997 ◽  
Vol 2 (2) ◽  
pp. 87-92 ◽  
Author(s):  
Akimi Uehata ◽  
Eric H Lieberman ◽  
Marie D Gerhard ◽  
Todd J Anderson ◽  
Peter Ganz ◽  
...  
Keyword(s):  
Blood Flow ◽  
Endothelial Function ◽  
Brachial Artery ◽  
Vascular Function ◽  
Reactive Hyperemia ◽  
Intraobserver Variability ◽  
Flow Mediated Dilation ◽  
Noninvasive Technique ◽  
Brachial Artery Diameter ◽  
Cuff Occlusion

Coronary atherosclerosis is characterized by an early loss of endothelium-dependent vasodilation. However, the methods of assessing coronary endothelial function are invasive and difficult to repeat over time. Recently, a noninvasive ultrasound method has been widely used to measure flow-mediated dilation in the brachial artery as a surrogate test for endothelial function. We seek to further validate this method of measuring vascular function. The brachial artery diameters and blood flow of 20 normal volunteers (10 males and 10 females) were measured using high resolution (7.5 MHz) ultrasound and strain gauge plethysmography. Flow-mediated endothelium-dependent vasodilation was measured in the brachial artery during reactive hyperemia after 5 minutes of cuff occlusion in the upper arm. The brachial artery diameter increased maximally by 9.7 ± 4.3% from baseline at 1 min after cuff release and blood flow increased by 1002 ± 376%. Five min of cuff occlusion was sufficient to achieve 97 ± 6% of maximal brachial artery dilation and degree of dilation was not different whether the cuff was inflated proximally or distally to the image site. The intraobserver variability in measuring brachial diameters was 2.9 % and the variability of the hyperemic response was 1.4%. In young, healthy men and women, the baseline brachial artery diameter was the only factor that was predictive of the flow-mediated vasodilation response. The brachial noninvasive technique has been further validated by the determination of flow-mediated dilation. This method of assessing endothelial function may help to determine the importance of vasodilator dysfunction as a risk factor in the development of atherosclerosis.

Effect of cardiac pacing on forearm vascular responses and nitric oxide function

2002 ◽  
Vol 283 (4) ◽  
pp. H1354-H1360 ◽  
Author(s):  
Daniel Green ◽  
Craig Cheetham ◽  
Chelsea Henderson ◽  
Rukshen Weerasooriya ◽  
Gerard O'Driscoll
Keyword(s):  
Nitric Oxide ◽  
Heart Rate ◽  
Blood Flow ◽  
Brachial Artery ◽  
Pulse Pressure ◽  
Forearm Blood Flow ◽  
Cardiac Pacing ◽  
Pulse Frequency ◽  
Brachial Artery Diameter

We examined the hypothesis that changes in heart rate at rest influence bioactivity of nitric oxide (NO) in humans by examining forearm blood flow responses during cardiac pacing in six subjects. Peak forearm and mean forearm blood flows across the cardiac cycle were continuously recorded at baseline and during pacing, with the use of high-resolution brachial artery ultrasound and Doppler flow velocity measurement. The brachial artery was cannulated to allow continuous infusion of saline or N G-monomethyl-l-arginine (l-NMMA). As heart rate increased, no changes in pulse pressure and mean or peak blood flow were evident. l-NMMA had no effect on brachial artery diameter, velocity, or flows compared with saline infusion. These results contrast with our recent findings that exercise involving the lower body, associated with increases in heart rate and pulse pressure, also increased forearm blood flow, the latter response being diminished by l-NMMA. These data suggest that changes in blood pressure, rather than pulse frequency, may be the stimulus for shear stress-mediated NO release in vivo.

Mixed meal and light exercise each recruit muscle capillaries in healthy humans

2006 ◽  
Vol 290 (6) ◽  
pp. E1191-E1197 ◽  
Author(s):  
Michelle A. Vincent ◽  
Lucy H. Clerk ◽  
Jonathan R. Lindner ◽  
Wendie J. Price ◽  
Linda A. Jahn ◽  
...  
Keyword(s):  
Blood Flow ◽  
Flow Velocity ◽  
Brachial Artery ◽  
Artery Blood Flow ◽  
Mixed Meal ◽  
Microvascular Flow ◽  
Nutrient Exchange ◽  
Healthy Humans ◽  
Artery Flow ◽  
Muscle Capillaries

Intense exercise and insulin each increases total limb blood flow and recruits muscle capillaries, presumably to facilitate nutrient exchange. Whether mixed meals or light exercise likewise recruits capillaries is unknown. We fed 18 (9 M, 9 F) healthy volunteers a 480-kcal liquid mixed meal. Plasma glucose, insulin, brachial artery flow, and forearm muscle microvascular blood volume were measured before and after the meal. Brachial artery flow and microvascular volume were also examined with light (25% max), moderate (50%), and heavy (80%) forearm contraction every 20 s in 5 (4 M, 1 F) healthy adults. After the meal, glucose and insulin rose modestly (to ∼7 mM and ∼270 pM) and peaked by 30 min, whereas brachial artery blood flow ( P < 0.05) and the microvascular volume ( P < 0.01) each increased significantly by 60 min, and microvascular flow velocity did not change. For exercise, both 50 and 80%, but not 25% maximal handgrip, increased average forearm and brachial artery blood flow ( P < 0.01). Flow increased immediately after each contraction and declined toward basal over 15 s. Exercise at 25% max increased microvascular volume threefold ( P < 0.01) without affecting microvascular flow velocity or total forearm blood flow. Forearm exercise at 80% maximal grip increased both microvascular volume and microvascular flow velocity ( P < 0.05 each). We conclude that light exercise and simple meals each markedly increases muscle microvascular volume, thereby expanding the endothelial surface for nutrient exchange, and that capillary recruitment is an important physiological response to facilitate nutrient/hormone delivery in healthy humans.

scholarly journals Exercise-induced brachial artery blood flow and vascular function is impaired in systemic sclerosis

2016 ◽  
Vol 311 (6) ◽  
pp. H1375-H1381 ◽  
Author(s):  
Daniel R. Machin ◽  
Heather L. Clifton ◽  
Ryan S. Garten ◽  
Jayson R. Gifford ◽  
Russell S. Richardson ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Blood Flow ◽  
Systemic Sclerosis ◽  
Brachial Artery ◽  
Vascular Function ◽  
Vascular Dysfunction ◽  
Artery Blood Flow ◽  
Handgrip Exercise ◽  
Brachial Artery Diameter ◽  
Exercise Induced

Systemic sclerosis (SSc) is a rare autoimmune disease characterized by debilitating fibrosis and vascular dysfunction; however, little is known about the circulatory response to exercise in this population. Therefore, we examined the peripheral hemodynamic and vasodilatory responses to handgrip exercise in 10 patients with SSc (61 ± 4 yr) and 15 age-matched healthy controls (56 ± 5 yr). Brachial artery diameter, blood flow, and mean arterial pressure (MAP) were determined at rest and during progressive static-intermittent handgrip exercise. Patients with SSc and controls were similar in body stature, handgrip strength, and MAP; however, brachial artery blood flow at rest was nearly twofold lower in patients with SSc compared with controls (22 ± 4 vs. 42 ± 5 ml/min, respectively; P < 0.05). Additionally, SSc patients had an ∼18% smaller brachial artery lumen diameter with an ∼28% thicker arterial wall at rest ( P < 0.05). Although, during handgrip exercise, there were no differences in MAP between the groups, exercise-induced hyperemia and therefore vascular conductance were ∼35% lower at all exercise workloads in patients with SSc ( P < 0.05). Brachial artery vasodilation, as assessed by the relationship between Δbrachial artery diameter and Δshear rate, was significantly attenuated in the patients with SSc ( P < 0.05). Finally, vascular dysfunction in the patients with SSc was accompanied by elevated blood markers of oxidative stress and attenuated endogenous antioxidant activity ( P < 0.05). Together, these findings reveal attenuated exercise-induced brachial artery blood flow and conduit arterial vasodilatory dysfunction during handgrip exercise in SSc and suggest that elevated oxidative stress may play a role.

Effect of head-out water immersion on vascular function in healthy subjects

2014 ◽  
Vol 39 (4) ◽  
pp. 425-431 ◽  
Author(s):  
Karine Ayme ◽  
Olivier Gavarry ◽  
Pascal Rossi ◽  
Anne-Virginie Desruelle ◽  
Jacques Regnard ◽  
...  
Keyword(s):  
Blood Flow ◽  
Smooth Muscle ◽  
Brachial Artery ◽  
Natriuretic Peptides ◽  
Vascular Function ◽  
Water Immersion ◽  
Ambient Air ◽  
Peripheral Blood Flow ◽  
Cell Reactivity ◽  
Brachial Artery Diameter

Immersion in thermoneutral water increases cardiac output and peripheral blood flow and reduces systemic vascular resistance. This study examined the effects of head-out water immersion on vascular function. Twelve healthy middle-aged males were immersed during 60 min in the seated position, with water at the level of xiphoid. Local and central vascular tone regulating systems were studied during that time. Brachial artery diameter and blood flow were recorded using ultrasonography and Doppler. Endothelial function was assessed with flow-mediated dilation. Results were compared with the same investigations performed under reference conditions in ambient air. During water immersion, brachial artery diameter increased (3.7 ± 0.2 mm in ambient air vs. 4 ± 0.2 mm in water immersion; p < 0.05). Endothelium-mediated dilation was significantly lower in water immersion than in ambient air (10% vs. 15%; p = 0.01). Nevertheless, the difference disappeared when the percentage vasodilatation of the brachial artery was normalized to the shear stimulus. Smooth muscle-mediated dilation was similar in the 2 conditions. Spectral analysis of systolic blood pressure variability indicated a decrease in sympathetic vascular activity. Plasma levels of nitric oxide metabolites remained unchanged, whereas levels of natriuretic peptides were significantly elevated. An increase in brachial blood flow, a decrease in sympathetic activity, a warming of the skin, and an increase in natriuretic peptides might be involved in the increase in reference diameter observed during water immersion. Endothelial cell reactivity and smooth muscle function did not appear to be altered.

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