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1.
J Cereb Blood Flow Metab ; 37(6): 2025-2034, 2017 Jun.
Article in English | MEDLINE | ID: mdl-27406213

ABSTRACT

The inability to quantify cerebral blood flow and changes in macrocirculation cross-sectional area in all brain regions impedes robust insight into hypoxic cerebral blood flow control. We applied four-dimensional flow magnetic resonance imaging to quantify cerebral blood flow (ml • min-1) and cross-sectional area (mm2) simultaneously in 11 arteries. In healthy adults, blood pressure, O2 Saturation (SpO2), and end-tidal CO2 were measured at baseline and steady-state hypoxia (FiO2 = 0.11). We investigated left and right: internal carotid, vertebral, middle, anterior, posterior cerebral arteries, and basilar artery. Hypoxia (SpO2 = 80±2%) increased total cerebral blood flow from 621±38 to 742±50 ml • min-1 ( p < 0.05). Hypoxia increased cerebral blood flow, except in the right posterior cerebral arteries. Hypoxia increased cross-sectional area in the anterior arteries (left and right internal carotid arteries, left and right middle, p < 0.05; left and right anterior p = 0.08) but only the right vertebral artery of the posterior circulation. Nonetheless, relative cerebral blood flow distribution and vascular reactivity (Δ%cerebral blood flow • ΔSpO2-1) were not different between arteries. Collectively, moderate hypoxia: (1) increased cerebral blood flow, but relative distribution remains similar to normoxia, (2) evokes similar vascular reactivity between 11 arteries, and (3) increased cross-sectional area primarily in the anterior arteries. This study provides the first wide-ranging, quantitative, functional and structural data regarding intracranial arteries during hypoxia in humans, highlighting cerebral blood flow regulation of microcirculation and macrocirculation differs between anterior and posterior circulation.


Subject(s)
Anterior Cerebral Artery/diagnostic imaging , Cerebrovascular Circulation/physiology , Hypoxia, Brain/physiopathology , Posterior Cerebral Artery/diagnostic imaging , Vasodilation/physiology , Adult , Anterior Cerebral Artery/physiopathology , Carbon Dioxide/metabolism , Female , Healthy Volunteers , Humans , Hypoxia, Brain/diagnostic imaging , Hypoxia, Brain/metabolism , Magnetic Resonance Imaging , Male , Microcirculation/physiology , Oxygen/metabolism , Posterior Cerebral Artery/physiopathology
2.
Eur J Appl Physiol ; 117(2): 237-246, 2017 Feb.
Article in English | MEDLINE | ID: mdl-28013386

ABSTRACT

PURPOSE: Previous work has shown nitric oxide (NO) contributes to ~15% of the hyperemic response to dynamic exercise in healthy humans. This NO-mediated vasodilation occurs, in part, via increases in intracellular cyclic guanosine monophosphate (cGMP), which is catabolized by phosphodiesterase. We sought to examine the effect of phosphodiesterase-5 (PDE-5) inhibition on forearm blood flow (FBF) responses to dynamic handgrip exercise in healthy humans and the role of NO. We hypothesized exercise hyperemia would be augmented by sildenafil citrate (SDF, PDE-5 inhibitor). We further hypothesized any effect of SDF on exercise hyperemia would be abolished with intra-arterial infusion of the NO synthase (NOS) inhibitor L-NG-monomethyl arginine (L-NMMA). METHODS: FBF (Doppler ultrasound) was assessed at rest and during 5 min of dynamic forearm handgrip exercise at 15% of maximal voluntary contraction under control (saline) conditions and during 3 experimental protocols: (1) oral SDF (n = 10), (2) intra-arterial L-NMMA (n = 20), (3) SDF and L-NMMA (n = 10). FBF responses to intra-arterial sodium nitroprusside (NTP, NO donor) were also assessed. RESULTS: FBF increased with exercise (p < 0.01). Intra-arterial infusion of L-NMMA resulted in a reduction in exercise hyperemia (17 ± 1 to 15 ± 1 mL/dL/min, p < 0.01). Although the hyperemic response to NTP was augmented by SDF (area under the curve: 41 ± 7 vs 61 ± 11 AU, p < 0.01), there was no effect of SDF on exercise hyperemia (p = 0.33). CONCLUSIONS: Despite improving NTP-mediated vasodilation, oral SDF failed to augment exercise hyperemia in young, healthy adults. These observations reflect a minor contribution of NO and the cGMP pathway during exercise hyperemia in healthy young humans.


Subject(s)
Blood Pressure/drug effects , Exercise/physiology , Hand Strength/physiology , Nitric Oxide/metabolism , Nucleotides, Cyclic/metabolism , Vasodilation/drug effects , Adult , Blood Pressure/physiology , Enzyme Inhibitors/pharmacology , Female , Hemodynamics/drug effects , Hemodynamics/physiology , Humans , Hyperemia/physiopathology , Male , Nitroprusside/pharmacology , Phosphodiesterase 5 Inhibitors/pharmacology , Sildenafil Citrate/administration & dosage , Sildenafil Citrate/pharmacology , Vasodilation/physiology , Young Adult
3.
Magn Reson Imaging ; 34(4): 422-8, 2016 May.
Article in English | MEDLINE | ID: mdl-26708027

ABSTRACT

UNLABELLED: Non-invasive measurement of cerebral blood flow (CBF) in humans is fraught with technologic, anatomic, and accessibility issues, which has hindered multi-vessel hemodynamic analysis of the cranial vasculature. Recent developments in cardiovascular MRI have allowed for the measurement of cine velocity vector fields over large imaging volumes in a single acquisition with 4D flow MRI. The purpose of this study was to develop an imaging protocol to simultaneously measure pulsatile flow in the circle of Willis as well as the carotid and vertebrate arteries at rest and during increased CO2 (hypercapnia). METHODS: 8 healthy adults (3 women, 26±0.4years) completed this study. Heart rate (pulse oximetry), arterial oxygen saturation (pulse oximetry), blood pressure (MAP, sphygmomanometry), and end-tidal CO2 (capnograph) were measured at rest (baseline) and during hypercapnia. Hypercapnia was induced via breathing a mixed gas of 3% CO2 and 21% O2 (balance N2) in the MR magnet. CBF and vessel cross-sectional area were quantified in 11 arteries using a 4D flow MRI scan, lasting 5-6min with a radially undersampled acquisition and an isotropic spatial resolution of 0.7mm. RESULTS: Baseline total CBF was 665±54ml • min(-1). Hypercapnia increased total CBF 9±3% to 721±61ml • min(-1). Hypercapnic increases in CBF ranged from 7 to 36% by artery, with the largest increases in the left anterior cerebral artery. Increases in artery cross-sectional area were observed in basilar and vertebral arteries. CONCLUSION: 4D flow MRI methods are sensitive enough to detect non-uniform changes in CBF and cross-sectional area to a mild yet clinically relevant CO2 stimulus. 4D flow MRI is a non-invasive reliable tool providing high spatio-temporal resolution in clinically feasible scan times without contrast agent. This approach can be used to interrogate regional cerebrovascular control in health and disease.


Subject(s)
Cerebrovascular Circulation/physiology , Hypercapnia/diagnostic imaging , Magnetic Resonance Imaging , Adult , Carbon Dioxide/blood , Carotid Arteries/diagnostic imaging , Circle of Willis/diagnostic imaging , Female , Humans , Image Processing, Computer-Assisted , Male , Oximetry , Oxygen/blood , Pulsatile Flow , Rest , Vertebral Artery/diagnostic imaging
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