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Proc Natl Acad Sci U S A. 2012 Jun 26;109(26):10181-6. doi: 10.1073/pnas.1204568109. Epub 2012 Jun 12.

Phase transitions in physiologic coupling.

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  • 1Harvard Medical School and Division of Sleep Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.


Integrated physiological systems, such as the cardiac and the respiratory system, exhibit complex dynamics that are further influenced by intrinsic feedback mechanisms controlling their interaction. To probe how the cardiac and the respiratory system adjust their rhythms, despite continuous fluctuations in their dynamics, we study the phase synchronization of heartbeat intervals and respiratory cycles. The nature of this interaction, its physiological and clinical relevance, and its relation to mechanisms of neural control is not well understood. We investigate whether and how cardiorespiratory phase synchronization (CRPS) responds to changes in physiological states and conditions. We find that the degree of CRPS in healthy subjects dramatically changes with sleep-stage transitions and exhibits a pronounced stratification pattern with a 400% increase from rapid eye movement sleep and wake, to light and deep sleep, indicating that sympatho-vagal balance strongly influences CRPS. For elderly subjects, we find that the overall degree of CRPS is reduced by approximately 40%, which has important clinical implications. However, the sleep-stage stratification pattern we uncover in CRPS does not break down with advanced age, and surprisingly, remains stable across subjects. Our results show that the difference in CRPS between sleep stages exceeds the difference between young and elderly, suggesting that sleep regulation has a significantly stronger effect on cardiorespiratory coupling than healthy aging. We demonstrate that CRPS and the traditionally studied respiratory sinus arrhythmia represent different aspects of the cardiorespiratory interaction, and that key physiologic variables, related to regulatory mechanisms of the cardiac and respiratory systems, which influence respiratory sinus arrhythmia, do not affect CRPS.

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