Publications by authors named "Graham M Fraser"

Objective: To determine if insulin-mediated hyperemia is partially dependent on local muscle oxygen concentration.

Methods: Sprague-Dawley rats were anesthetized, and the extensor digitorum longus (EDL) was reflected onto an inverted microscope. Intravital video microscopy sequences were recorded during baseline and hyperinsulinemic euglycemia.

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We aimed to quantify the magnitude and time transients of capillary blood flow responses to acute changes in local oxygen concentration ([O]), and carbon dioxide concentration ([CO]) in skeletal muscle. Additionally, we sought to quantify the combined response to both low [O] and high [CO] to mimic muscle microenvironment changes at the onset of exercise. 13 Sprague Dawley rats were anaesthetized, mechanically ventilated, and instrumented with indwelling catheters for systemic monitoring.

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Endothelium dysfunction produces peripheral vascular disease comorbidities in type 2 diabetes, including hypertension, and critical limb ischemia. In this study we aimed to test endothelial dysfunction, the vasodilator effects of a proteinase-activated receptor 2 (PAR2) agonist (2fLIGRLO), and thromboxane A synthase inhibitor (ozagrel) on PAR2 vasodilation in hind limb arteries ex vivo, using Zucker Diabetic-Sprague Dawley (ZDSD) rats, a model of type 2 diabetes. Male Sprague Dawley rats (SD) and ZDSD were fed a high-fat content 'Western diet' from 16 to 20 weeks of age (wks) then fed a standard laboratory diet.

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Ageing is associated with reduced endothelium-derived nitric oxide (NO) production in the femoral artery of Sprague Dawley (SD) rats. In the current study, we examined endothelium-dependent relaxation (EDR) in the saphenous artery and its caudal branches. We used acetylcholine and the Proteinase-Activated receptor-2 (PAR2)-specific agonist (2fLIGRLO) with nitroarginine methylester (L-NAME) to assess EDR in two groups of male SD rats (age in weeks: young, 10-12; old, 27-29).

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New Findings: What is the topic of this review? The Zucker Diabetic-Sprague Dawley (ZDSD) rat is in the early adoption phase of use by researchers in the fields of diabetes, including prediabetes, obesity and metabolic syndrome. It is essential that physiology researchers choose preclinical models that model human type 2 diabetes appropriately and are aware of the limitations on experimental design. What advances does it highlight? Our review of the scientific literature finds that although sex, age and diets contribute to variability, the ZDSD phenotype and disease progression model the characteristics of humans who have prediabetes and diabetes, including co-morbidities.

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Objective: The aim of this study was to develop a tool to visualize and quantify hemodynamic information, such as hemoglobin concentration and hematocrit, within microvascular networks recorded in vivo using intravital video microscopy. Additionally, we aimed to facilitate the 3-D reconstruction of the microvascular networks.

Methods: Digital images taken from an intravital video microscopy preparation of the extensor digitorum longus muscle in rats for 25 capillary segments were used.

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Purpose: Following an acute exposure to hypoxia, sympathetic nerve activity remains elevated. However, this elevated sympathetic nerve activity does not elicit a parallel increase in vascular resistance suggesting a blunted sympathetic signaling [i.e.

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Intravital microscopy has proven to be a powerful tool for studying microvascular physiology. In this study, we propose a gas exchange system compatible with intravital microscopy that can be used to impose gas perturbations to small localized regions in skeletal muscles or other tissues that can be imaged using conventional inverted microscopes. We demonstrated the effectiveness of this system by locally manipulating oxygen concentrations in rat muscle and measuring the resulting vascular responses.

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Unlabelled: How oxygen (O ) supply to capillaries is regulated to match the tissue's demand is unknown. Erythrocytes have been proposed as sensors in this regulatory mechanism since they release ATP, a vasodilator, in an oxygen saturation (SO )-dependent manner. ATP causes hyperpolarization of endothelial cells resulting in conducted vasodilation to arterioles.

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Objective: To develop and validate a novel liquid microfluidic approach to deliver drugs to microscale regions of tissue while simultaneously allowing for visualization and quantification of microvascular blood flow.

Methods: Microfluidic devices were fabricated using soft lithographic techniques, molded in polydimethylsiloxane, and bound to a coverslip with a 600 × 300 μm micro-outlet. Sprague-Dawley rats, anesthetized with pentobarbital, were instrumented to monitor systemic parameters.

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The relationship between sympathetic nerve activity and the vasculature has been of great interest due to its potential role in various cardiovascular-related diseases. This relationship, termed "sympathetic transduction," has been quantified using several different laboratory and analytical techniques. The most common method is to assess the association between relative changes in muscle sympathetic nerve activity, measured via microneurography, and physiological outcomes (e.

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Purpose: Obstructive sleep apnea (OSA) is a common disorder (~ 4%) that augments sympathetic nerve activity (SNA) and elevates blood pressure. The relationship between sympathetic vasomotor outflow and vascular responsiveness, termed sympathetic neurovascular transduction (sNVT), has been sparsely characterized in patients with OSA. Therefore, we sought to quantify spontaneous sympathetic bursts and related changes in diastolic pressure.

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Purpose: Women who develop gestational hypertension have evidence of elevated muscle sympathetic nerve activity (MSNA) in early pregnancy, which continues to rise after diagnosis. Exercise has been shown to play a preventative role in the development of gestational hypertension and has been shown to reduce resting and reflex MSNA in nonpregnant populations. We sought to investigate whether aerobic exercise affected the sympathetic regulation of blood pressure between the second and third trimesters of pregnancy.

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Isometric handgrip (IHG) is used to assess sympathetic nervous system responses to exercise and may be useful at predicting hypertension in both pregnant and nonpregnant populations. We previously observed altered sympathetic nervous system control of blood pressure in late pregnancy. Therefore, we measured muscle sympathetic nerve activity (MSNA) and blood pressure during muscle metaboreflex activation (IHG) in normotensive pregnant women in the third trimester compared with in healthy nonpregnant women.

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High-altitude (>2,500 m) exposure results in increased muscle sympathetic nervous activity (MSNA) in acclimatizing lowlanders. However, little is known about how altitude affects MSNA in indigenous high-altitude populations. Additionally, the relationship between MSNA and blood pressure regulation (i.

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It has been suggested that sex differences in acute blood pressure fluctuations occur during the periods of time between bursts of muscle sympathetic nerve activity. Therefore, we tested the hypothesis that men experience more dynamic changes in mean arterial pressure (Finometer MIDI) than women during acute sympathoinhibition (i.e.

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Objective: The effect of insulin on blood flow distribution within muscle microvasculature has been suggested to be important for glucose metabolism. However, the "capillary recruitment" hypothesis is still controversial and relies on studies using indirect contrast-enhanced ultrasound (CEU) methods.

Methods: We studied how hyperinsulinemia effects capillary blood flow in rat extensor digitorum longus (EDL) muscle during euglycemic hyperinsulinemic clamp using intravital video microscopy (IVVM).

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Key Points: Normotensive pregnancy is associated with elevated sympathetic nervous system activity yet normal or reduced blood pressure. It represents a unique period of apparent healthy sympathetic hyperactivity. The present study models the blood pressure and heart rate (ECG R-R interval) responses to fluctuations in sympathetic nervous system activity aiming to understand neurocardiovascular transduction.

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Red blood cell oxygen saturation (SO ) is an important indicator of oxygen supply to tissues in the body. SO can be measured by taking advantage of spectroscopic properties of hemoglobin. When this technique is applied to transmission microscopy, the calculation of saturation requires determination of incident light intensity at each pixel occupied by the red blood cell; this value is often approximated from a sequence of images as the maximum intensity over time.

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Research suggests that spatial ability may predict success in complex disciplines including anatomy, where mastery requires a firm understanding of the intricate relationships occurring along the course of veins, arteries, and nerves, as they traverse through and around bones, muscles, and organs. Debate exists on the malleability of spatial ability, and some suggest that spatial ability can be enhanced through training. It is hypothesized that spatial ability can be trained in low-performing individuals through visual guidance.

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Individuals with an aptitude for interpreting spatial information (high mental rotation ability: HMRA) typically master anatomy with more ease, and more quickly, than those with low mental rotation ability (LMRA). This article explores how visual attention differs with time limits on spatial reasoning tests. Participants were assorted to two groups based on their mental rotation ability scores and their eye movements were collected during these tests.

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Rationale: Angiogenesis occurs after ischemic injury to skeletal muscle, and enhancing this response has been a therapeutic goal. However, to appropriately deliver oxygen, a precisely organized and exquisitely responsive microcirculation must form. Whether these network attributes exist in a regenerated microcirculation is unknown, and methodologies for answering this have been lacking.

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Objectives: The purpose of this study was to model how CD variability affects tissue oxygenation under resting and exercise conditions. Additionally, we examine how CD impacts glucose and insulin transport in skeletal muscle.

Methods: We applied an established 3D finite difference model of oxygen transport to predict tissue oxygenation using FCD, hemodynamics, and SO measurements from a previous study.

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