Faculty Opinions recommendation of Postprandial microvascular blood flow in skeletal muscle: Similarities and disparities to the hyperinsulinaemic-euglycaemic clamp.

2020 ◽  
Author(s):  
Ann Louise Olson
Keyword(s):  
Skeletal Muscle ◽  
Blood Flow ◽  
Microvascular Blood Flow ◽  
Euglycaemic Clamp ◽  
Hyperinsulinaemic Euglycaemic Clamp

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

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 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.

scholarly journals Oral glucose challenge impairs skeletal muscle microvascular blood flow in healthy people

2018 ◽  
Vol 315 (2) ◽  
pp. E307-E315 ◽  
Author(s):  
Ryan D. Russell ◽  
Donghua Hu ◽  
Timothy Greenaway ◽  
James E. Sharman ◽  
Stephen Rattigan ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Skeletal Muscle ◽  
Blood Flow ◽  
Healthy People ◽  
Microvascular Blood Flow ◽  
Glucose Disposal ◽  
Oral Glucose ◽  
Large Artery ◽  
Acute Hyperglycemia ◽  
Glucose Challenge

Skeletal muscle microvascular (capillary) blood flow increases in the postprandial state or during insulin infusion due to dilation of precapillary arterioles to augment glucose disposal. This effect occurs independently of changes in large artery function. However, acute hyperglycemia impairs vascular function, causes insulin to vasoconstrict precapillary arterioles, and causes muscle insulin resistance in vivo. We hypothesized that acute hyperglycemia impairs postprandial muscle microvascular perfusion, without disrupting normal large artery hemodynamics, in healthy humans. Fifteen healthy people (5 F/10 M) underwent an oral glucose challenge (OGC, 50 g glucose) and a mixed-meal challenge (MMC) on two separate occasions (randomized, crossover design). At 1 h, both challenges produced a comparable increase (6-fold) in plasma insulin levels. However, the OGC produced a 1.5-fold higher increase in blood glucose compared with the MMC 1 h postingestion. Forearm muscle microvascular blood volume and flow (contrast-enhanced ultrasound) were increased during the MMC (1.3- and 1.9-fold from baseline, respectively, P < 0.05 for both) but decreased during the OGC (0.7- and 0.6-fold from baseline, respectively, P < 0.05 for both) despite a similar hyperinsulinemia. Both challenges stimulated brachial artery flow (ultrasound) and heart rate to a similar extent, as well as yielding comparable decreases in diastolic blood pressure and total vascular resistance. Systolic blood pressure and aortic stiffness remained unaltered by either challenge. Independently of large artery hemodynamics, hyperglycemia impairs muscle microvascular blood flow, potentially limiting glucose disposal into skeletal muscle. The OGC reduced microvascular blood flow in muscle peripherally and therefore may underestimate the importance of skeletal muscle in postprandial glucose disposal.

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