Relationship between cardiorespiratory phase coherence during hypoxia and genetic polymorphism in humans.

Details

Serval ID
serval:BIB_83A465B1998F
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Relationship between cardiorespiratory phase coherence during hypoxia and genetic polymorphism in humans.
Journal
The Journal of physiology
Author(s)
Lancaster G., Debevec T., Millet G.P., Poussel M., Willis S.J., Mramor M., Goričar K., Osredkar D., Dolžan V., Stefanovska A.
ISSN
1469-7793 (Electronic)
ISSN-L
0022-3751
Publication state
Published
Issued date
05/2020
Peer-reviewed
Oui
Volume
598
Number
10
Pages
2001-2019
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
High altitude-induced hypoxia in humans evokes a pattern of breathing known as periodic breathing (PB), in which the regular oscillations corresponding to rhythmic expiration and inspiration are modulated by slow periodic oscillations. The phase coherence between instantaneous heart rate and respiration is shown to increase significantly at the frequency of periodic breathing during acute and sustained normobaric and hypobaric hypoxia. It is also shown that polymorphism in specific genes, NOTCH4 and CAT, is significantly correlated with this coherence, and thus with the incidence of PB. Differences in phase shifts between blood flow signals and respiratory and PB oscillations clearly demonstrate contrasting origins of the mechanisms underlying normal respiration and PB. These novel findings provide a better understanding of both the genetic and the physiological mechanisms responsible for respiratory control during hypoxia at altitude, by linking genetic factors with cardiovascular dynamics, as evaluated by phase coherence.
Periodic breathing (PB) occurs in most humans at high altitudes and is characterised by low-frequency periodic alternation between hyperventilation and apnoea. In hypoxia-induced PB the dynamics and coherence between heart rate and respiration and their relationship to underlying genetic factors is still poorly understood. The aim of this study was to investigate, through novel usage of time-frequency analysis methods, the dynamics of hypoxia-induced PB in healthy individuals genotyped for a selection of antioxidative and neurodevelopmental genes. Breathing, ECG and microvascular blood flow were simultaneously monitored for 30 min in 22 healthy males. The same measurements were repeated under normoxic and hypoxic (normobaric (NH) and hypobaric (HH)) conditions, at real and simulated altitudes of up to 3800 m. Wavelet phase coherence and phase difference around the frequency of breathing (approximately 0.3 Hz) and around the frequency of PB (approximately 0.06 Hz) were evaluated. Subjects were genotyped for common functional polymorphisms in antioxidative and neurodevelopmental genes. During hypoxia, PB resulted in increased cardiorespiratory coherence at the PB frequency. This coherence was significantly higher in subjects with NOTCH4 polymorphism, and significantly lower in those with CAT polymorphism (HH only). Study of the phase shifts clearly indicates that the physiological mechanism of PB is different from that of the normal respiratory cycle. The results illustrate the power of time-evolving oscillatory analysis content in obtaining important insight into high altitude physiology. In particular, it provides further evidence for a genetic predisposition to PB and may partly explain the heterogeneity in the hypoxic response.
Keywords
Altitude, Altitude Sickness, Humans, Hypoxia/genetics, Polymorphism, Genetic, Respiration, CAT, NOTCH4, cardiovascular dynamics, heart rate variability, hypoxia, periodic breathing, wavelet analysis
Pubmed
Web of science
Open Access
Yes
Create date
22/02/2021 14:15
Last modification date
24/02/2022 7:34
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