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Relationship between cardiorespiratory phase coherence during hypoxia and genetic polymorphism in humans: Genetic predisposition to hypoxia induced periodic breathing

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<mark>Journal publication date</mark>15/01/2020
<mark>Journal</mark>The Journal of Physiology
Publication statusAccepted/In press
Original languageEnglish

Abstract

Periodic breathing (PB) occurs in most humans at high altitudes and is characterised by lowfrequency 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 minutes 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.