Journal of cardiovascular pharmacology and therapeutics, Jan 12, 2015
The nitric oxide synthase (NOS)-independent pathway of nitric oxide (NO) production in which nitr... more The nitric oxide synthase (NOS)-independent pathway of nitric oxide (NO) production in which nitrite (NO2 (-)) is reduced to NO may have therapeutic applications for those with cardiovascular diseases in which the NOS pathway is downregulated. We tested the hypothesis that NO2 (-) infusion would reduce mean arterial pressure (MAP) and increase skeletal muscle blood flow (BF) and vascular conductance (VC) during exercise in the face of NOS blockade via L-NAME. Following infusion of L-NAME (10 mg kg(-1), L-NAME), male Sprague-Dawley rats (3-6 months, n = 8) exercised without N(G)-nitro-L arginine methyl ester (L-NAME) and after infusion of sodium NO2 (-) (7 mg kg(-1); L-NAME + NO2 (-)). MAP and hindlimb skeletal muscle BF (radiolabeled microsphere infusions) were measured during submaximal treadmill running (20 m min(-1), 5% grade). Across group comparisons were made with a published control data set (n = 11). Relative to L-NAME, NO2 (-) infusion significantly reduced MAP (P < 0.03...
Peripheral blood-derived endothelial cells (pBD-ECs) are an attractive tool for cell therapies an... more Peripheral blood-derived endothelial cells (pBD-ECs) are an attractive tool for cell therapies and tissue engineering, but have been limited by their low isolation yield. We increase pBD-EC yield via administration of the chemokine receptor type 4 antagonist AMD3100, as well as via a diluted whole blood incubation (DWBI). Porcine pBD-ECs were isolated using AMD3100 and DWBI and tested for EC markers, acetylated LDL uptake, growth kinetics, metabolic activity, flow-mediated nitric oxide production and seeded onto titanium tubes implanted into vessels of pigs. DWBI increased the yield of porcine pBD-ECs 6.6-fold, and AMD3100 increased the yield 4.5-fold. AMD3100-mobilized ECs were phenotypically indistinguishable from nonmobilized ECs. In porcine implants, the cells expressed endothelial nitric oxide synthase, reduced thrombin-antithrombin complex systemically and prevented thrombosis. Administration of AMD3100 and the DWBI method both increase pBD-EC yield.
It is now recognised that administration of oral nitrate (NO3(-)), in its various forms, increase... more It is now recognised that administration of oral nitrate (NO3(-)), in its various forms, increases the level of nitric oxide (NO) metabolites in the circulation of humans. Its application to modulate physiology and alleviate cardiovascular dysfunction in some patients is now recorded and shows particular promise in hypertension, in modifying platelet activation/aggregation, and in conditions where tissue ischaemia prevails. The potential of oral NO3(-) to modify exercise/performance via elevation of plasma nitrite concentration ([NO2(-)]) has been applied across a range of human test systems. Herein we discuss how the choice of NO3(-) source, route of administration and resulting pharmacokinetics might influence the outcome of physiological measures and potentially contribute to discrepancies in performance trials. There are but a few examples of detailed pharmacokinetic data on which the majority of researchers base their test protocols in different cohorts/settings. We compare and contrast the results of key publications with the aim of highlighting a consensus of our current understanding and critical considerations for those entering the field.
The purpose was to determine the influence of a unilateral localized short-term handgrip training... more The purpose was to determine the influence of a unilateral localized short-term handgrip training protocol on brachial artery flow-mediated dilation (BAFMD) and to examine the time course of such changes. Fourteen healthy males (age: 26 +/- 5.7 yr) underwent high-resolution ultrasonographic brachial artery assessments before (V1), during (V2-V7), and at the end of 4 wk (V8) of 60% maximal voluntary contraction handgrip training (20 min.d-1, 5 d.wk-1) of the nondominant arm. Before training resting diameters were similar between the trained (nondominant) and untrained (dominant) arms. A 2 (trained and untrained arms) x 2 (V1 and V8) repeated measure ANOVA revealed a significant main (P = 0.02 and P = 0.03) and interaction effect (P = 0.05 and P = 0.01) for the percent and absolute change in BAFMD. BAFMD improved 62% and 70%, respectively from V1 to V8, for the percent and absolute change. Subsequent linear orthogonal polynomial contrasts indicate both the percent and absolute change ...
Atherosclerotic disease in the carotid artery is a risk factor for stroke. The susceptibility of ... more Atherosclerotic disease in the carotid artery is a risk factor for stroke. The susceptibility of atherosclerotic plaque to rupture, however, is challenging to determine by any imaging method. In this study, acoustic radiation force impulse (ARFI) imaging is applied to atherosclerotic disease in the carotid artery to determine the feasibility of using ARFI to noninvasively characterize carotid plaques. ARFI imaging is a useful method for characterizing the local mechanical properties of tissue and is complementary to B-mode imaging. ARFI imaging can readily distinguish between stiff and soft regions of tissue. High-resolution images of both homogeneous and heterogeneous plaques were observed. Homogeneous plaques were indistinguishable in stiffness from vascular tissue. However, they showed thicknesses much greater than normal vascular tissue. In heterogeneous plaques, large and small soft regions were observed, with the smallest observed soft region having a diameter of 0.5 mm. A sti...
ABSTRACT Using detailed loan transactions-level data we examine the efficiency of an overnight in... more ABSTRACT Using detailed loan transactions-level data we examine the efficiency of an overnight interbank lending market, and the bargaining power of its participants. Our analysis relies on the equilibrium concept of the core, which imposes a set of no-arbitrage conditions on trades in the market. For Canada we show that while the market is fairly efficient, some degree of inefficiency persists throughout our sample. The level of inefficiency matches distinct phases of both the Bank of Canada’s operations as well as phases of the 2007-2008 financial crisis, where more liquidity intervention implies more inefficiency. We find that bargaining power tilted sharply towards borrowers as the financial crisis progressed, and towards riskier borrowers. This supports a nuanced version of the Too-Big-To-Fail story, whereby participants continued to lend to riskier banks at favorable rates, not because of explicit support to the riskier banks provided by governmental authorities, but rather due to the collective self-interest of these banks.
Nitric oxide : biology and chemistry / official journal of the Nitric Oxide Society, Jan 2, 2014
Nitrate (NO3(-)) supplementation via beetroot juice (BR) preferentially improves vascular conduct... more Nitrate (NO3(-)) supplementation via beetroot juice (BR) preferentially improves vascular conductance and O2 delivery to contracting skeletal muscles comprised predominantly of type IIb + d/x (i.e. highly glycolytic) fibers following its reduction to nitrite and nitric oxide (NO). To address the mechanistic basis for NO3(-) to improve metabolic control we tested the hypothesis that BR supplementation would elevate microvascular PO2 (PO2mv) in fast twitch but not slow twitch muscle. Twelve young adult male Sprague-Dawley rats were administered BR ([NO3(-)] 1 mmol/kg/day, n = 6) or water (control, n = 6) for 5 days. PO2mv (phosphorescence quenching) was measured at rest and during 180 s of electrically-induced 1-Hz twitch contractions (6-8 V) of the soleus (9% type IIb +d/x) and mixed portion of the gastrocnemius (MG, 91% type IIb + d/x) muscles. In the MG, but not the soleus, BR elevated contracting steady state PO2mv by ~43% (control: 14 ± 1, BR: 19 ± 2 mmHg (P <0.05)). This high...
Page 1. Peripheral Vascular ARFI Imaging: Phantom and Clinical Results Douglas Dumont, Elizabeth ... more Page 1. Peripheral Vascular ARFI Imaging: Phantom and Clinical Results Douglas Dumont, Elizabeth Miller, Jason David Allen, Christian Moyer, Stephen Hsu, Gregg Trahey Duke University, Durham, NC 27708 dmd@duke.edu ...
Journal of cardiovascular pharmacology and therapeutics, Jan 12, 2015
The nitric oxide synthase (NOS)-independent pathway of nitric oxide (NO) production in which nitr... more The nitric oxide synthase (NOS)-independent pathway of nitric oxide (NO) production in which nitrite (NO2 (-)) is reduced to NO may have therapeutic applications for those with cardiovascular diseases in which the NOS pathway is downregulated. We tested the hypothesis that NO2 (-) infusion would reduce mean arterial pressure (MAP) and increase skeletal muscle blood flow (BF) and vascular conductance (VC) during exercise in the face of NOS blockade via L-NAME. Following infusion of L-NAME (10 mg kg(-1), L-NAME), male Sprague-Dawley rats (3-6 months, n = 8) exercised without N(G)-nitro-L arginine methyl ester (L-NAME) and after infusion of sodium NO2 (-) (7 mg kg(-1); L-NAME + NO2 (-)). MAP and hindlimb skeletal muscle BF (radiolabeled microsphere infusions) were measured during submaximal treadmill running (20 m min(-1), 5% grade). Across group comparisons were made with a published control data set (n = 11). Relative to L-NAME, NO2 (-) infusion significantly reduced MAP (P < 0.03...
Peripheral blood-derived endothelial cells (pBD-ECs) are an attractive tool for cell therapies an... more Peripheral blood-derived endothelial cells (pBD-ECs) are an attractive tool for cell therapies and tissue engineering, but have been limited by their low isolation yield. We increase pBD-EC yield via administration of the chemokine receptor type 4 antagonist AMD3100, as well as via a diluted whole blood incubation (DWBI). Porcine pBD-ECs were isolated using AMD3100 and DWBI and tested for EC markers, acetylated LDL uptake, growth kinetics, metabolic activity, flow-mediated nitric oxide production and seeded onto titanium tubes implanted into vessels of pigs. DWBI increased the yield of porcine pBD-ECs 6.6-fold, and AMD3100 increased the yield 4.5-fold. AMD3100-mobilized ECs were phenotypically indistinguishable from nonmobilized ECs. In porcine implants, the cells expressed endothelial nitric oxide synthase, reduced thrombin-antithrombin complex systemically and prevented thrombosis. Administration of AMD3100 and the DWBI method both increase pBD-EC yield.
It is now recognised that administration of oral nitrate (NO3(-)), in its various forms, increase... more It is now recognised that administration of oral nitrate (NO3(-)), in its various forms, increases the level of nitric oxide (NO) metabolites in the circulation of humans. Its application to modulate physiology and alleviate cardiovascular dysfunction in some patients is now recorded and shows particular promise in hypertension, in modifying platelet activation/aggregation, and in conditions where tissue ischaemia prevails. The potential of oral NO3(-) to modify exercise/performance via elevation of plasma nitrite concentration ([NO2(-)]) has been applied across a range of human test systems. Herein we discuss how the choice of NO3(-) source, route of administration and resulting pharmacokinetics might influence the outcome of physiological measures and potentially contribute to discrepancies in performance trials. There are but a few examples of detailed pharmacokinetic data on which the majority of researchers base their test protocols in different cohorts/settings. We compare and contrast the results of key publications with the aim of highlighting a consensus of our current understanding and critical considerations for those entering the field.
The purpose was to determine the influence of a unilateral localized short-term handgrip training... more The purpose was to determine the influence of a unilateral localized short-term handgrip training protocol on brachial artery flow-mediated dilation (BAFMD) and to examine the time course of such changes. Fourteen healthy males (age: 26 +/- 5.7 yr) underwent high-resolution ultrasonographic brachial artery assessments before (V1), during (V2-V7), and at the end of 4 wk (V8) of 60% maximal voluntary contraction handgrip training (20 min.d-1, 5 d.wk-1) of the nondominant arm. Before training resting diameters were similar between the trained (nondominant) and untrained (dominant) arms. A 2 (trained and untrained arms) x 2 (V1 and V8) repeated measure ANOVA revealed a significant main (P = 0.02 and P = 0.03) and interaction effect (P = 0.05 and P = 0.01) for the percent and absolute change in BAFMD. BAFMD improved 62% and 70%, respectively from V1 to V8, for the percent and absolute change. Subsequent linear orthogonal polynomial contrasts indicate both the percent and absolute change ...
Atherosclerotic disease in the carotid artery is a risk factor for stroke. The susceptibility of ... more Atherosclerotic disease in the carotid artery is a risk factor for stroke. The susceptibility of atherosclerotic plaque to rupture, however, is challenging to determine by any imaging method. In this study, acoustic radiation force impulse (ARFI) imaging is applied to atherosclerotic disease in the carotid artery to determine the feasibility of using ARFI to noninvasively characterize carotid plaques. ARFI imaging is a useful method for characterizing the local mechanical properties of tissue and is complementary to B-mode imaging. ARFI imaging can readily distinguish between stiff and soft regions of tissue. High-resolution images of both homogeneous and heterogeneous plaques were observed. Homogeneous plaques were indistinguishable in stiffness from vascular tissue. However, they showed thicknesses much greater than normal vascular tissue. In heterogeneous plaques, large and small soft regions were observed, with the smallest observed soft region having a diameter of 0.5 mm. A sti...
ABSTRACT Using detailed loan transactions-level data we examine the efficiency of an overnight in... more ABSTRACT Using detailed loan transactions-level data we examine the efficiency of an overnight interbank lending market, and the bargaining power of its participants. Our analysis relies on the equilibrium concept of the core, which imposes a set of no-arbitrage conditions on trades in the market. For Canada we show that while the market is fairly efficient, some degree of inefficiency persists throughout our sample. The level of inefficiency matches distinct phases of both the Bank of Canada’s operations as well as phases of the 2007-2008 financial crisis, where more liquidity intervention implies more inefficiency. We find that bargaining power tilted sharply towards borrowers as the financial crisis progressed, and towards riskier borrowers. This supports a nuanced version of the Too-Big-To-Fail story, whereby participants continued to lend to riskier banks at favorable rates, not because of explicit support to the riskier banks provided by governmental authorities, but rather due to the collective self-interest of these banks.
Nitric oxide : biology and chemistry / official journal of the Nitric Oxide Society, Jan 2, 2014
Nitrate (NO3(-)) supplementation via beetroot juice (BR) preferentially improves vascular conduct... more Nitrate (NO3(-)) supplementation via beetroot juice (BR) preferentially improves vascular conductance and O2 delivery to contracting skeletal muscles comprised predominantly of type IIb + d/x (i.e. highly glycolytic) fibers following its reduction to nitrite and nitric oxide (NO). To address the mechanistic basis for NO3(-) to improve metabolic control we tested the hypothesis that BR supplementation would elevate microvascular PO2 (PO2mv) in fast twitch but not slow twitch muscle. Twelve young adult male Sprague-Dawley rats were administered BR ([NO3(-)] 1 mmol/kg/day, n = 6) or water (control, n = 6) for 5 days. PO2mv (phosphorescence quenching) was measured at rest and during 180 s of electrically-induced 1-Hz twitch contractions (6-8 V) of the soleus (9% type IIb +d/x) and mixed portion of the gastrocnemius (MG, 91% type IIb + d/x) muscles. In the MG, but not the soleus, BR elevated contracting steady state PO2mv by ~43% (control: 14 ± 1, BR: 19 ± 2 mmHg (P <0.05)). This high...
Page 1. Peripheral Vascular ARFI Imaging: Phantom and Clinical Results Douglas Dumont, Elizabeth ... more Page 1. Peripheral Vascular ARFI Imaging: Phantom and Clinical Results Douglas Dumont, Elizabeth Miller, Jason David Allen, Christian Moyer, Stephen Hsu, Gregg Trahey Duke University, Durham, NC 27708 dmd@duke.edu ...
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