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      Neurovascular coupling and cerebral autoregulation in atrial fibrillation

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          Abstract

          The risk of cognitive decline and stroke is increased by atrial fibrillation (AF). We sought to determine whether neurovascular coupling and cerebral autoregulation are blunted in people with AF in comparison with age-matched, patients with hypertension and healthy controls. Neurovascular coupling was assessed using five cycles of visual stimulation for 30 s followed by 30 s with both eyes-closed. Cerebral autoregulation was examined using a sit–stand test, and a repeated squat-to-stand (0.1 Hz) manoeuvre with transfer function analysis of mean arterial pressure (MAP; input) and middle cerebral artery mean blood flow velocity (MCA V m; output) relationships at 0.1 Hz. Visual stimulation increased posterior cerebral artery conductance, but the magnitude of the response was blunted in patients with AF (18 [8] %; mean [SD]) and hypertension (17 [8] %), in comparison with healthy controls (26 [9] %) ( P < 0.05). In contrast, transmission of MAP to MCA V m was greater in AF patients compared to hypertension and healthy controls, indicating diminished cerebral autoregulation. We have shown for the first time that AF patients have impaired neurovascular coupling responses to visual stimulation and diminished cerebral autoregulation. Such deficits in cerebrovascular regulation may contribute to the increased risk of cerebral dysfunction in people with AF.

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          Neurovascular coupling in the normal brain and in hypertension, stroke, and Alzheimer disease.

          The brain is critically dependent on a continuous supply of blood to function. Therefore, the cerebral vasculature is endowed with neurovascular control mechanisms that assure that the blood supply of the brain is commensurate to the energy needs of its cellular constituents. The regulation of cerebral blood flow (CBF) during brain activity involves the coordinated interaction of neurons, glia, and vascular cells. Thus, whereas neurons and glia generate the signals initiating the vasodilation, endothelial cells, pericytes, and smooth muscle cells act in concert to transduce these signals into carefully orchestrated vascular changes that lead to CBF increases focused to the activated area and temporally linked to the period of activation. Neurovascular coupling is disrupted in pathological conditions, such as hypertension, Alzheimer disease, and ischemic stroke. Consequently, CBF is no longer matched to the metabolic requirements of the tissue. This cerebrovascular dysregulation is mediated in large part by the deleterious action of reactive oxygen species on cerebral blood vessels. A major source of cerebral vascular radicals in models of hypertension and Alzheimer disease is the enzyme NADPH oxidase. These findings, collectively, highlight the importance of neurovascular coupling to the health of the normal brain and suggest a therapeutic target for improving brain function in pathologies associated with cerebrovascular dysfunction.
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            Integrative regulation of human brain blood flow.

            Herein, we review mechanisms regulating cerebral blood flow (CBF), with specific focus on humans. We revisit important concepts from the older literature and describe the interaction of various mechanisms of cerebrovascular control. We amalgamate this broad scope of information into a brief review, rather than detailing any one mechanism or area of research. The relationship between regulatory mechanisms is emphasized, but the following three broad categories of control are explicated: (1) the effect of blood gases and neuronal metabolism on CBF; (2) buffering of CBF with changes in blood pressure, termed cerebral autoregulation; and (3) the role of the autonomic nervous system in CBF regulation. With respect to these control mechanisms, we provide evidence against several canonized paradigms of CBF control. Specifically, we corroborate the following four key theses: (1) that cerebral autoregulation does not maintain constant perfusion through a mean arterial pressure range of 60-150 mmHg; (2) that there is important stimulatory synergism and regulatory interdependence of arterial blood gases and blood pressure on CBF regulation; (3) that cerebral autoregulation and cerebrovascular sensitivity to changes in arterial blood gases are not modulated solely at the pial arterioles; and (4) that neurogenic control of the cerebral vasculature is an important player in autoregulatory function and, crucially, acts to buffer surges in perfusion pressure. Finally, we summarize the state of our knowledge with respect to these areas, outline important gaps in the literature and suggest avenues for future research.
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              Nitric oxide is responsible for flow-dependent dilatation of human peripheral conduit arteries in vivo.

              Experimental evidence suggests that flow-dependent dilatation of conduit arteries is mediated by nitric oxide (NO) and/or prostacyclin. The present study was designed to assess whether NO or prostacyclin also contributes to flow-dependent dilatation of conduit arteries in humans. Radial artery internal diameter (ID) was measured continuously in 16 healthy volunteers (age, 24 +/- 1 years) with a transcutaneous A-mode echo-tracking system coupled to a Doppler device for the measurement of radial blood flow. In 8 subjects, a catheter was inserted into the brachial artery for measurement of arterial pressure and infusion of the NO synthase inhibitor NG-monomethyl-L-arginine (L-NMMA; 8 mumol/min for 7 minutes; infusion rate, 0.8 mL/min). Flow-dependent dilatation was evaluated before and after L-NMMA or aspirin as the response of the radial artery to an acute increase in flow (reactive hyperemia after a 3-minute cuff wrist occlusion). Under control conditions, release of the occlusion induced a marked increase in radial blood flow (from 24 +/- 3 to 73 +/- 11 mL/min; P < .01) followed by a delayed increase in radial diameter (flow-mediated dilatation; from 2.67 +/- 0.10 to 2.77 +/- 0.12 mm; P < .01) without any change in heart rate or arterial pressure. L-NMMA decreased basal forearm blood flow (from 24 +/- 3 to 13 +/- 3 mL/min; P < .05) without affecting basal radial artery diameter, heart rate, or arterial pressure, whereas aspirin (1 g PO) was without any hemodynamic effect. In the presence of L-NMMA, the peak flow response during hyperemia was not affected (76 +/- 12 mL/min), but the duration of the hyperemic response was markedly reduced, and the flow-dependent dilatation of the radial artery was abolished and converted to a vasoconstriction (from 2.62 +/- 0.11 to 2.55 +/- 0.11 mm; P < .01). In contrast, aspirin did not affect the hyperemic response nor the flow-dependent dilatation of the radial artery. The present investigation demonstrates that NO, but not prostacyclin, is essential for flow-mediated dilatation of large human arteries. Hence, this response can be used as a test for the L-arginine/NO pathway in clinical studies.
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                Author and article information

                Journal
                J Cereb Blood Flow Metab
                J. Cereb. Blood Flow Metab
                JCB
                spjcb
                Journal of Cerebral Blood Flow & Metabolism
                SAGE Publications (Sage UK: London, England )
                0271-678X
                1559-7016
                19 August 2019
                August 2020
                19 August 2019
                : 40
                : 8
                : 1647-1657
                Affiliations
                [1 ]School of Sport, Exercise & Rehabilitation Sciences, College of Life & Environmental Sciences, University of Birmingham, Birmingham, UK
                [2 ]Liverpool Centre for Cardiovascular Science, Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, UK
                [3 ]Medical School, University Center of Volta Redonda, Volta Redonda, Brazil
                [4 ]Centre for Human Brain Health, College of Life & Environmental Sciences, University of Birmingham, Birmingham, UK
                [5 ]Department of Internal Medicine, University of Amsterdam, Amsterdam, The Netherlands
                [6 ]Laboratory for Clinical Cardiovascular Physiology, AMC Center for Heart Failure Research, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
                [7 ]MRC/Arthritis Research UK Centre for Musculoskeletal Ageing Research, School of Life Sciences, University of Nottingham Medical School, Queen's Medical Centre, Nottingham, UK
                [8 ]Departments of Physiology, Pharmacology & Clinical Neurosciences, Libin Cardiovascular Institute, Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Alberta, Canada
                [9 ]Department of Physiology, Faculty of Medical & Health Sciences, University of Auckland, Auckland, New Zealand
                Author notes
                [*]James P Fisher, Department of Physiology, Faculty of Medical & Health Sciences, University of Auckland, Park Road, Grafton, Auckland 1142, New Zealand. Email: jp.fisher@ 123456auckland.ac.nz
                Author information
                https://orcid.org/0000-0002-0670-8339
                Article
                10.1177_0271678X19870770
                10.1177/0271678X19870770
                7370373
                31426699
                192d52a8-1444-4fa6-8f86-452401d24a0a
                © The Author(s) 2019

                This article is distributed under the terms of the Creative Commons Attribution 4.0 License ( http://www.creativecommons.org/licenses/by/4.0/) which permits any use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages ( https://us.sagepub.com/en-us/nam/open-access-at-sage).

                History
                : 22 April 2019
                : 15 July 2019
                : 24 July 2019
                Categories
                Original Articles
                Custom metadata
                ts2

                Neurosciences
                aging,atrial fibrillation,brain,cerebral circulation,hypertension
                Neurosciences
                aging, atrial fibrillation, brain, cerebral circulation, hypertension

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