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Measuring Peripheral Chemoreflex Hypersensitivity in Heart Failure

Heart failure with reduced ejection fraction (HFrEF) induces chronic sympathetic activation. This disturbance is a consequence of both compensatory reflex disinhibition in response to lower cardiac output and patient-specific activation of one or more excitatory stimuli. The result is the net adrene...

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Autores principales: Keir, Daniel A., Duffin, James, Floras, John S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7802759/
https://www.ncbi.nlm.nih.gov/pubmed/33447244
http://dx.doi.org/10.3389/fphys.2020.595486
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author Keir, Daniel A.
Duffin, James
Floras, John S.
author_facet Keir, Daniel A.
Duffin, James
Floras, John S.
author_sort Keir, Daniel A.
collection PubMed
description Heart failure with reduced ejection fraction (HFrEF) induces chronic sympathetic activation. This disturbance is a consequence of both compensatory reflex disinhibition in response to lower cardiac output and patient-specific activation of one or more excitatory stimuli. The result is the net adrenergic output that exceeds homeostatic need, which compromises cardiac, renal, and vascular function and foreshortens lifespan. One such sympatho-excitatory mechanism, evident in ~40–45% of those with HFrEF, is the augmentation of carotid (peripheral) chemoreflex ventilatory and sympathetic responsiveness to reductions in arterial oxygen tension and acidosis. Recognition of the contribution of increased chemoreflex gain to the pathophysiology of HFrEF and to patients’ prognosis has focused attention on targeting the carotid body to attenuate sympathetic drive, alleviate heart failure symptoms, and prolong life. The current challenge is to identify those patients most likely to benefit from such interventions. Two assumptions underlying contemporary test protocols are that the ventilatory response to acute hypoxic exposure quantifies accurately peripheral chemoreflex sensitivity and that the unmeasured sympathetic response mirrors the determined ventilatory response. This Perspective questions both assumptions, illustrates the limitations of conventional transient hypoxic tests for assessing peripheral chemoreflex sensitivity and demonstrates how a modified rebreathing test capable of comprehensively quantifying both the ventilatory and sympathoneural efferent responses to peripheral chemoreflex perturbation, including their sensitivities and recruitment thresholds, can better identify individuals most likely to benefit from carotid body intervention.
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spelling pubmed-78027592021-01-13 Measuring Peripheral Chemoreflex Hypersensitivity in Heart Failure Keir, Daniel A. Duffin, James Floras, John S. Front Physiol Physiology Heart failure with reduced ejection fraction (HFrEF) induces chronic sympathetic activation. This disturbance is a consequence of both compensatory reflex disinhibition in response to lower cardiac output and patient-specific activation of one or more excitatory stimuli. The result is the net adrenergic output that exceeds homeostatic need, which compromises cardiac, renal, and vascular function and foreshortens lifespan. One such sympatho-excitatory mechanism, evident in ~40–45% of those with HFrEF, is the augmentation of carotid (peripheral) chemoreflex ventilatory and sympathetic responsiveness to reductions in arterial oxygen tension and acidosis. Recognition of the contribution of increased chemoreflex gain to the pathophysiology of HFrEF and to patients’ prognosis has focused attention on targeting the carotid body to attenuate sympathetic drive, alleviate heart failure symptoms, and prolong life. The current challenge is to identify those patients most likely to benefit from such interventions. Two assumptions underlying contemporary test protocols are that the ventilatory response to acute hypoxic exposure quantifies accurately peripheral chemoreflex sensitivity and that the unmeasured sympathetic response mirrors the determined ventilatory response. This Perspective questions both assumptions, illustrates the limitations of conventional transient hypoxic tests for assessing peripheral chemoreflex sensitivity and demonstrates how a modified rebreathing test capable of comprehensively quantifying both the ventilatory and sympathoneural efferent responses to peripheral chemoreflex perturbation, including their sensitivities and recruitment thresholds, can better identify individuals most likely to benefit from carotid body intervention. Frontiers Media S.A. 2020-12-29 /pmc/articles/PMC7802759/ /pubmed/33447244 http://dx.doi.org/10.3389/fphys.2020.595486 Text en Copyright © 2020 Keir, Duffin and Floras. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Physiology
Keir, Daniel A.
Duffin, James
Floras, John S.
Measuring Peripheral Chemoreflex Hypersensitivity in Heart Failure
title Measuring Peripheral Chemoreflex Hypersensitivity in Heart Failure
title_full Measuring Peripheral Chemoreflex Hypersensitivity in Heart Failure
title_fullStr Measuring Peripheral Chemoreflex Hypersensitivity in Heart Failure
title_full_unstemmed Measuring Peripheral Chemoreflex Hypersensitivity in Heart Failure
title_short Measuring Peripheral Chemoreflex Hypersensitivity in Heart Failure
title_sort measuring peripheral chemoreflex hypersensitivity in heart failure
topic Physiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7802759/
https://www.ncbi.nlm.nih.gov/pubmed/33447244
http://dx.doi.org/10.3389/fphys.2020.595486
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