scholarly journals Prior exercise enhances skeletal muscle microvascular blood flow and mitigates microvascular flow impairments induced by a high‐glucose mixed meal in healthy young men

2020 ◽  
Vol 599 (1) ◽  
pp. 83-102 ◽  
Author(s):  
Lewan Parker ◽  
Dale J. Morrison ◽  
Glenn D. Wadley ◽  
Christopher S. Shaw ◽  
Andrew C. Betik ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Blood Flow ◽  
High Glucose ◽  
Young Men ◽  
Microvascular Blood Flow ◽  
Mixed Meal ◽  
Microvascular Flow ◽  
Prior Exercise

scholarly journals High-glucose mixed-nutrient meal ingestion impairs skeletal muscle microvascular blood flow in healthy young men

2020 ◽  
Vol 318 (6) ◽  
pp. E1014-E1021 ◽  
Author(s):  
Lewan Parker ◽  
Dale J. Morrison ◽  
Andrew C. Betik ◽  
Katherine Roberts-Thomson ◽  
Gunveen Kaur ◽  
...  
Keyword(s):  
Blood Flow ◽  
Blood Glucose ◽  
High Glucose ◽  
Young Men ◽  
Arterial Blood Flow ◽  
Thigh Muscle ◽  
Microvascular Blood Flow ◽  
Arterial Blood ◽  
Glucose Ingestion ◽  
Meal Ingestion

Oral glucose ingestion leads to impaired muscle microvascular blood flow (MBF), which may contribute to acute hyperglycemia-induced insulin resistance. We investigated whether incorporating lipids and protein into a high-glucose load would prevent postprandial MBF dysfunction. Ten healthy young men (age, 27 yr [24, 30], mean with lower and upper bounds of the 95% confidence interval; height, 180 cm [174, 185]; weight, 77 kg [70, 84]) ingested a high-glucose (1.1 g/kg glucose) mixed-nutrient meal (10 kcal/kg; 45% carbohydrate, 20% protein, and 35% fat) in the morning after an overnight fast. Femoral arterial blood flow was measured via Doppler ultrasound, and thigh MBF was measured via contrast-enhanced ultrasound, before meal ingestion and 1 h and 2 h postprandially. Blood glucose and plasma insulin were measured at baseline and every 15 min throughout the 2-h postprandial period. Compared with baseline, thigh muscle microvascular blood volume, velocity, and flow were significantly impaired at 60 min postprandial (−25%, −27%, and −46%, respectively; all P < 0.05) and to a greater extent at 120 min postprandial (−37%, −46%, and −64%; all P < 0.01). Heart rate and femoral arterial diameter, blood velocity, and blood flow were significantly increased at 60 min and 120 min postprandial (all P < 0.05). Higher blood glucose area under the curve was correlated with greater MBF dysfunction ( R2 = 0.742; P < 0.001). Ingestion of a high-glucose mixed-nutrient meal impairs MBF in healthy individuals for up to 2 h postprandial.

scholarly journals Pharmacological enhancement of leg and muscle microvascular blood flow does not augment anabolic responses in skeletal muscle of young men under fed conditions

2014 ◽  
Vol 306 (2) ◽  
pp. E168-E176 ◽  
Author(s):  
Bethan E. Phillips ◽  
Philip J. Atherton ◽  
Krishna Varadhan ◽  
Daniel J. Wilkinson ◽  
Marie Limb ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Blood Flow ◽  
Blood Volume ◽  
Femoral Artery ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Young Men ◽  
Microvascular Blood Flow ◽  
Gas Chromatography Mass Spectrometry ◽  
Fed State

Skeletal muscle anabolism associated with postprandial plasma aminoacidemia and insulinemia is contingent upon amino acids (AA) and insulin crossing the microcirculation-myocyte interface. In this study, we hypothesized that increasing muscle microvascular blood volume (flow) would enhance fed-state anabolic responses in muscle protein turnover. We studied 10 young men (23.2 ± 2.1 yr) under postabsorptive and fed [iv Glamin (∼10 g AA), glucose ∼7.5 mmol/l] conditions. Methacholine was infused into the femoral artery of one leg to determine, via bilateral comparison, the effects of feeding alone vs. feeding plus pharmacological vasodilation. We measured leg blood flow (LBF; femoral artery) by Doppler ultrasound, muscle microvascular blood volume (MBV) by contrast-enhanced ultrasound (CEUS), muscle protein synthesis (MPS) and breakdown (MPB; a-v balance modeling), and net protein balance (NPB) using [1,2-13C2]leucine and [2H5]phenylalanine tracers via gas chromatography-mass spectrometry (GC-MS). Indexes of anabolic signaling/endothelial activation (e.g., Akt/mTORC1/NOS) were assessed using immunoblotting techniques. Under fed conditions, LBF (+12 ± 5%, P < 0.05), MBV (+25 ± 10%, P < 0.05), and MPS (+129 ± 33%, P < 0.05) increased. Infusion of methacholine further enhanced LBF (+126 ± 12%, P < 0.05) and MBV (+79 ± 30%, P < 0.05). Despite these radically different blood flow conditions, neither increases in MPS in response to feeding (0.04 ± 0.004 vs. 0.08 ± 0.01%/h, P < 0.05) nor improvements in NPB (−4.4 ± 2.4 vs. 16.4 ± 5.7 nmol Phe·100 ml leg−1·min−1, P < 0.05) were affected by methacholine infusion (MPS 0.07 ± 0.01%/h; NPB 24.0 ± 7.7 nmol Phe·100 ml leg−1·min−1), whereas MPB was unaltered by either feeding or infusion of methacholine. Thus, enhancing LBF/MBV above that occurring naturally with feeding alone does not improve muscle anabolism.

Higher Myocardial and Skeletal Muscle Microvascular Flow in Sickle Cell Disease Patients on Hydroxyurea

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 1020-1020
Author(s):  
Caterina P. Minniti ◽  
Vandana Sachdev ◽  
Hannoush Hwaida ◽  
Stanislav Sidenko ◽  
Myron A Waclawiw ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Skeletal Muscle ◽  
Blood Flow ◽  
Sickle Cell ◽  
Brachial Artery ◽  
Organ Damage ◽  
Microvascular Blood Flow ◽  
Muscle Perfusion ◽  
Microvascular Flow ◽  
Beneficial Effects

Abstract Individuals with SCD have recurrent episodes of ischemia-reperfusion in vital organs, and abnormal microcirculation is considered a major determinant of end organ damage. Hydroxyurea (HU) treatment has been shown to produce ATP- and nitric oxide-mediated vasodilation, and to improve red cells deformability Few tools are available to quantitatively measure microvascular blood flow in vivo. The purpose of this study was to assess the ability of a novel ECHO based imaging modality to assess the effect of hydroxyurea on cardiac and skeletal muscle perfusion in patients with sickle cell anemia. Methods and Results: Twenty-one HBSS/B0 patients, of whom 15 were treated with HU(average daily dose of 18 ± 8 mg/kg/day), underwent brachial artery ultrasound, echocardiography and contrast enhanced ultrasound (CEU) perfusion imaging of deep flexor muscles of the forearm as well as the myocardium at rest and during vasodilator stress with regadenoson ( ClinicalTrials.gov NCT016028090). Quantitative image analysis was performed to obtain microvascular blood volume and flow velocity measurements. Patients on HU had a lower white blood cell count (6.7±2.1 K/uL vs 10.0±2.1 K/uL, p<0.05), higher mean corpuscular volume (103.6±11.5 fL vs 82.5±8.6 fL, p<0.05) , and lower reticulocyte count (9.3±3.4% vs 15.7±5.6%, p<0.05) as well as a trend towards higher hemoglobin (9.4±1.4g/dL vs 7.9±1.1g/dL , p=NS). Table 1. Cardiac output and total myocardial work was not affected by HU treatment and macrovascular flow in the brachial artery was not affected (Figure 1A). In contrast, both skeletal muscle microvascular flow and myocardial microvascular flow was significantly higher in the SCD patients on HU therapy (Figure 1B, 1C). Conclusions: The beneficial effects of HU therapy in SCD are varied, and clinical effects are often seen prior to a rise in fetal hemoglobin. Other effects, such as lower hemolysis, improved red cell deformability, and inhibition of adhesive properties in the microvasculature have been reported. Some of the beneficial effects of HU may be due to stimulation of nitric oxide synthase, induction of cyclic GMP dependent signaling and improved NO bioavailability. Our study indicates that SCD patients on chronic HU therapy have higher levels of myocardial and skeletal muscle microvascular blood flow. Long term studies are necessary to evaluate whether HU reduces end organ damage in SCA. Skeletal muscle and myocardial microvascular blood flow. Each panel shows blood flow in all SCD patients (red filled diamonds), SCD patients not on HU (red open triangles) and SCD patients on HU (red open inverted triangles). Panel A. Skeletal muscle perfusion normalized to hemoglobin (A x β x hemoglobin) Panel B. Myocardial perfusion normalized to hemoglobin level and total myocardial work. Figure 1. Figure 1. Disclosures No relevant conflicts of interest to declare.

cGMP phosphodiesterase inhibition improves the vascular and metabolic actions of insulin in skeletal muscle

2011 ◽  
Vol 301 (2) ◽  
pp. E342-E350 ◽  
Author(s):  
A. J. Genders ◽  
E. A. Bradley ◽  
S. Rattigan ◽  
S. M. Richards
Keyword(s):  
Skeletal Muscle ◽  
Blood Flow ◽  
Glucose Uptake ◽  
Mrna Level ◽  
Microvascular Perfusion ◽  
Microvascular Blood Flow ◽  
Whole Body ◽  
Acute Administration ◽  
Dependent Inhibition ◽  
Promising Avenue

There is considerable support for the concept that insulin-mediated increases in microvascular blood flow to muscle impact significantly on muscle glucose uptake. Since the microvascular blood flow increases with insulin have been shown to be nitric oxide-dependent inhibition of cGMP-degrading phosphodiesterases (cGMP PDEs) is predicted to enhance insulin-mediated increases in microvascular perfusion and muscle glucose uptake. Therefore, we studied the effects of the pan-cGMP PDE inhibitor zaprinast on the metabolic and vascular actions of insulin in muscle. Hyperinsulinemic euglycemic clamps (3 mU·min−1·kg−1) were performed in anesthetized rats and changes in microvascular blood flow assessed from rates of 1-methylxanthine metabolism across the muscle bed by capillary xanthine oxidase in response to insulin and zaprinast. We also characterized cGMP PDE isoform expression in muscle by real-time PCR and immunostaining of frozen muscle sections. Zaprinast enhanced insulin-mediated microvascular perfusion by 29% and muscle glucose uptake by 89%, while whole body glucose infusion rate during insulin infusion was increased by 33% at 2 h. PDE2, -9, and -10 were the major isoforms expressed at the mRNA level in muscle, while PDE1B, -9A, -10A, and -11A proteins were expressed in blood vessels. Acute administration of the cGMP PDE inhibitor zaprinast enhances muscle microvascular blood flow and glucose uptake response to insulin. The expression of a number of cGMP PDE isoforms in skeletal muscle suggests that targeting specific cGMP PDE isoforms may provide a promising avenue for development of a novel class of therapeutics for enhancing muscle insulin sensitivity.

scholarly journals Acute, local infusion of angiotensin II impairs microvascular and metabolic insulin sensitivity in skeletal muscle

2018 ◽  
Vol 115 (3) ◽  
pp. 590-601 ◽  
Author(s):  
Dino Premilovac ◽  
Emily Attrill ◽  
Stephen Rattigan ◽  
Stephen M Richards ◽  
Jeonga Kim ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Blood Pressure ◽  
Skeletal Muscle ◽  
Heart Rate ◽  
Blood Flow ◽  
Glucose Uptake ◽  
Microvascular Blood Flow ◽  
Euglycaemic Clamp ◽  
Hyperinsulinaemic Euglycaemic Clamp ◽  
Skeletal Muscle Glucose Uptake

Abstract Aims Angiotensin II (AngII) is a potent vasoconstrictor implicated in both hypertension and insulin resistance. Insulin dilates the vasculature in skeletal muscle to increase microvascular blood flow and enhance glucose disposal. In the present study, we investigated whether acute AngII infusion interferes with insulin’s microvascular and metabolic actions in skeletal muscle. Methods and results Adult, male Sprague-Dawley rats received a systemic infusion of either saline, AngII, insulin (hyperinsulinaemic euglycaemic clamp), or insulin (hyperinsulinaemic euglycaemic clamp) plus AngII. A final, separate group of rats received an acute local infusion of AngII into a single hindleg during systemic insulin (hyperinsulinaemic euglycaemic clamp) infusion. In all animals’ systemic metabolic effects, central haemodynamics, femoral artery blood flow, microvascular blood flow, and skeletal muscle glucose uptake (isotopic glucose) were monitored. Systemic AngII infusion increased blood pressure, decreased heart rate, and markedly increased circulating glucose and insulin concentrations. Systemic infusion of AngII during hyperinsulinaemic euglycaemic clamp inhibited insulin-mediated suppression of hepatic glucose output and insulin-stimulated microvascular blood flow in skeletal muscle but did not alter insulin’s effects on the femoral artery or muscle glucose uptake. Local AngII infusion did not alter blood pressure, heart rate, or circulating glucose and insulin. However, local AngII inhibited insulin-stimulated microvascular blood flow, and this was accompanied by reduced skeletal muscle glucose uptake. Conclusions Acute infusion of AngII significantly alters basal haemodynamic and metabolic homeostasis in rats. Both local and systemic AngII infusion attenuated insulin’s microvascular actions in skeletal muscle, but only local AngII infusion led to reduced insulin-stimulated muscle glucose uptake. While increased local, tissue production of AngII may be a factor that couples microvascular insulin resistance and hypertension, additional studies are needed to determine the molecular mechanisms responsible for these vascular defects.

scholarly journals Postprandial microvascular blood flow in skeletal muscle: Similarities and disparities to the hyperinsulinaemic‐euglycaemic clamp

2020 ◽  
Vol 47 (4) ◽  
pp. 725-737 ◽  
Author(s):  
Katherine M. Roberts‐Thomson ◽  
Andrew C. Betik ◽  
Dino Premilovac ◽  
Stephen Rattigan ◽  
Stephen M. Richards ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Blood Flow ◽  
Microvascular Blood Flow ◽  
Euglycaemic Clamp ◽  
Hyperinsulinaemic Euglycaemic Clamp

scholarly journals Characterization of the Skeletal Muscle Microvascular Blood Flow Response to Tissue CO 2 Perturbations using a Gas Exchange Chamber

2021 ◽  
Vol 35 (S1) ◽  
Author(s):  
Meaghan McCarthy ◽  
Meghan Kiley ◽  
Gaylene Russell McEvoy ◽  
Brenda Wells ◽  
Graham Fraser
Keyword(s):  
Skeletal Muscle ◽  
Blood Flow ◽  
Gas Exchange ◽  
Microvascular Blood Flow ◽  
Blood Flow Response ◽  
Flow Response

scholarly journals Acute cocoa flavanol supplementation improves muscle macro- and microvascular but not anabolic responses to amino acids in older men

2016 ◽  
Vol 41 (5) ◽  
pp. 548-556 ◽  
Author(s):  
Bethan E. Phillips ◽  
Philip J. Atherton ◽  
Krishna Varadhan ◽  
Marie C. Limb ◽  
John P. Williams ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Blood Flow ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Older Men ◽  
Microvascular Blood Flow ◽  
Older Individuals ◽  
Tracer Techniques ◽  
Vascular Responsiveness ◽  
Cocoa Flavanols

The anabolic effects of nutrition on skeletal muscle may depend on adequate skeletal muscle perfusion, which is impaired in older people. Cocoa flavanols have been shown to improve flow-mediated dilation, an established measure of endothelial function. However, their effect on muscle microvascular blood flow is currently unknown. Therefore, the objective of this study was to explore links between the consumption of cocoa flavanols, muscle microvascular blood flow, and muscle protein synthesis (MPS) in response to nutrition in older men. To achieve this objective, leg blood flow (LBF), muscle microvascular blood volume (MBV), and MPS were measured under postabsorptive and postprandial (intravenous Glamin (Fresenius Kabi, Germany), dextrose to sustain glucose ∼7.5 mmol·L−1) conditions in 20 older men. Ten of these men were studied with no cocoa flavanol intervention and a further 10 were studied with the addition of 350 mg of cocoa flavanols at the same time that nutrition began. Leg (femoral artery) blood flow was measured by Doppler ultrasound, muscle MBV by contrast-enhanced ultrasound using Definity (Lantheus Medical Imaging, Mass., USA) perflutren contrast agent and MPS using [1, 2-13C2]leucine tracer techniques. Our results show that although older individuals do not show an increase in LBF or MBV in response to feeding, these absent responses are apparent when cocoa flavanols are given acutely with nutrition. However, this restoration in vascular responsiveness is not associated with improved MPS responses to nutrition. We conclude that acute cocoa flavanol supplementation improves muscle macro- and microvascular responses to nutrition, independently of modifying muscle protein anabolism.

scholarly journals Contrast-Enhanced Ultrasound Detects Differences in Microvascular Blood Flow in Adults with Sickle Cell Disease Administered Regadenoson

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2705-2705
Author(s):  
Jonathan R. Lindner ◽  
Michael Widlansky ◽  
Melinda D. Wu ◽  
Jillian Dargatz ◽  
Leanne M. Harmann ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Blood Flow ◽  
Steady State ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Microvascular Blood Flow ◽  
Study Cohort ◽  
Cell Disease ◽  
Non Invasive ◽  
Contrast Enhanced

Abstract Background: Outcome measures for therapeutic studies in patients with sickle cell disease (SCD) are poor.Abnormal microvascular blood flow (MBF), the basis for tissue ischemia and injury associated with vaso-occlusion, would be an optimal outcome measure for SCD studies. Ideally, a modality to measure blood flow in SCD would non-invasively quantify microvascular tissue perfusion rather than assess conduit arterial flow through large vessels. Limitations of existing techniques to measure blood flow prevent their widespread use in clinical trials of patients with SCD. Contrast-enhanced ultrasound (CEU) is a non-invasive and portable technique that uses standard ultrasound equipment to measure microvascular perfusion and functional capillary patency. The primary objective of this study was to determine whether CEU is able to detect differences in the MBF of skeletal muscle: 1) before and after infusion with the adenosine A2A receptor (A2AR) agonist regadenoson, and 2) between steady state and vaso-occlusive crisis (VOC). Methods: CEU measurements were obtained in forearm skeletal muscle in adult HbSS patients. Two measures are used to calculate MBF: 1) velocity of RBCs through capillaries and 2) volume of blood perfused in an area of tissue. MBF is the product of RBC velocity and volume of blood. In one study cohort, MBF was measured in steady-state patients during a 24-hour infusion of regadenoson (1.44 µg/kg/hour). CEU perfusion imaging was obtained at baseline, 6 and 24 hours after initiation of regadenoson. In the second study cohort, CEU measurements were obtained within the same patient during a hospital admission for VOC and at steady state. MBF was expressed in terms of a ratio to baseline flow (pre-regadenoson) in cohort 1 and as a ratio of VOC to steady-state flow for cohort 2. Results: CEU measurements were obtained in13 patients administered regadenoson, and 7 patients at steady state and during VOC. Median age (range) of all patients studied was 24 years (20-45) and 55% were female. During regadenoson infusion, there was a median increase in skeletal muscle MBF of 29% at 6 hours (ratio 1.29, IQR 0.81) and 9% at 24 hours (ratio 1.09, IQR 1.40). Increase in MBF during regadenoson administration was largely due to higher RBC velocity (6 hours ratio: 1.24, IQR 0.88; 24 hours: ratio 1.12 IQR 0.85). There was a median decrease of 40% in skeletal muscle blood flow during VOC compared to steady state (ratio 0.60, IQR 0.27). Similarly, a decrease in RBC velocity accounted for most of the reduction in MBF in VOC compared to steady state (ratio 0.63, IQR 0.35). Conclusion: CEU measures of skeletal muscle MBF increased during a 24-hour infusion of regadenoson and decreased in VOC compared to steady state. Changes in RBC velocity, as opposed to the volume of blood perfused, accounted for most of the differences in MBF seen during regadenoson infusion and VOC. Alterations in rheology or vascular tone could explain these changes. These data provide additional evidence for the A2AR agonist regadenoson as a therapeutic modality for patients with SCD and suggest that CEU is a valid measure of blood flow in VOC. Taken together, the findings of this preliminary study demonstrate that CEU, a non-invasive, portable technique to measure MBF, could be used as an objective outcome measure for therapeutic studies in SCD. Disclosures Field: NKTT: Consultancy, Research Funding. Off Label Use: IND for regadenoson for treatment of VOC in sickle cell disease.

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