{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T05:39:29Z","timestamp":1791351569392,"version":"4.3.1"},"reference-count":70,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2020,2,26]],"date-time":"2020-02-26T00:00:00Z","timestamp":1582675200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000266","name":"Engineering and Physical Sciences Research Council","doi-asserted-by":"publisher","award":["EP\/M006298\/1"],"award-info":[{"award-number":["EP\/M006298\/1"]}],"id":[{"id":"10.13039\/501100000266","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004329","name":"Javna Agencija za Raziskovalno Dejavnost RS","doi-asserted-by":"publisher","award":["P20232"],"award-info":[{"award-number":["P20232"]}],"id":[{"id":"10.13039\/501100004329","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004329","name":"Javna Agencija za Raziskovalno Dejavnost RS","doi-asserted-by":"publisher","award":["J3\u20107536"],"award-info":[{"award-number":["J3\u20107536"]}],"id":[{"id":"10.13039\/501100004329","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2020,5]]},"abstract":"<jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>High altitude\u2010induced 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.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>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.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>It is also shown that polymorphism in specific genes, <jats:italic>NOTCH4<\/jats:italic> and <jats:italic>CAT<\/jats:italic>, is significantly correlated with this coherence, and thus with the incidence of PB.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>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.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>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.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec><jats:sec><jats:title>Abstract<\/jats:title><jats:p>Periodic breathing (PB) occurs in most humans at high altitudes and is characterised by low\u2010frequency periodic alternation between hyperventilation and apnoea. In hypoxia\u2010induced 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\u2013frequency analysis methods, the dynamics of hypoxia\u2010induced PB in healthy individuals genotyped for a selection of antioxidative and neurodevelopmental genes. Breathing, ECG and microvascular blood flow were simultaneously monitored for 30\u00a0min 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\u00a0m. Wavelet phase coherence and phase difference around the frequency of breathing (approximately 0.3\u00a0Hz) and around the frequency of PB (approximately 0.06\u00a0Hz) 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 <jats:italic>NOTCH4<\/jats:italic> polymorphism, and significantly lower in those with <jats:italic>CAT<\/jats:italic> 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\u2010evolving 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.<\/jats:p><\/jats:sec>","DOI":"10.1113\/jp278829","type":"journal-article","created":{"date-parts":[[2020,1,20]],"date-time":"2020-01-20T10:59:29Z","timestamp":1579517969000},"page":"2001-2019","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Relationship between cardiorespiratory phase coherence during hypoxia and genetic polymorphism in humans"],"prefix":"10.1113","volume":"598","author":[{"given":"Gemma","family":"Lancaster","sequence":"first","affiliation":[{"name":"Department of Physics Lancaster University  Lancaster UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7053-3978","authenticated-orcid":false,"given":"Tadej","family":"Debevec","sequence":"additional","affiliation":[{"name":"Faculty of Sport University of 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