Phase Synchronization of Hemodynamic Variables at Rest and after Deep Breathing Measured during the Course of Pregnancy Manfred Georg Moertl 1,2. , Helmut Karl Lackner 3,4 * . , Ilona Papousek 5 , Andreas Roessler 3 , Helmut Hinghofer-Szalkay 3 , Uwe Lang 1 , Vassiliki Kolovetsiou-Kreiner 1 , Dietmar Schlembach 1,6. 1 Department of Obstetrics and Gynecology, Medical University of Graz, Graz, Austria, 2 Department of Obstetrics and Gynecology, Clinical Center, Klagenfurt, Austria, 3 Department of Physiology, Medical University of Graz, Graz, Austria, 4 Department of Medical Engineering, Graz University of Technology, Graz, Austria, 5 Department of Psychology, Biological Psychology Unit, Karl-Franzens University, Graz, Austria, 6 Department of Obstetrics and Gynecology, Friedrich Schiller University, University Clinics Jena, Jena, Germany Abstract Background: The autonomic nervous system plays a central role in the functioning of systems critical for the homeostasis maintenance. However, its role in the cardiovascular adaptation to pregnancy-related demands is poorly understood. We explored the maternal cardiovascular systems throughout pregnancy to quantify pregnancy-related autonomic nervous system adaptations. Methodology: Continuous monitoring of heart rate (R-R interval; derived from the 3-lead electrocardiography), blood pressure, and thoracic impedance was carried out in thirty-six women at six time-points throughout pregnancy. In order to quantify in addition to the longitudinal effects on baseline levels throughout gestation the immediate adaptive heart rate and blood pressure changes at each time point, a simple reflex test, deep breathing, was applied. Consequently, heart rate variability and blood pressure variability in the low (LF) and high (HF) frequency range, respiration and baroreceptor sensitivity were analyzed in resting conditions and after deep breathing. The adjustment of the rhythms of the R-R interval, blood pressure and respiration partitioned for the sympathetic and the parasympathetic branch of the autonomic nervous system were quantified by the phase synchronization index c, which has been adopted from the analysis of weakly coupled chaotic oscillators. Results: Heart rate and LF/HF ratio increased throughout pregnancy and these effects were accompanied by a continuous loss of baroreceptor sensitivity. The increases in heart rate and LF/HF ratio levels were associated with an increasing decline in the ability to flexibly respond to additional demands (i.e., diminished adaptive responses to deep breathing). The phase synchronization index c showed that the observed effects could be explained by a decreased coupling of respiration and the cardiovascular system (HF components of heart rate and blood pressure). Conclusions/Significance: The findings suggest that during the course of pregnancy the individual systems become increasingly independent to meet the increasing demands placed on the maternal cardiovascular and respiratory system. Citation: Moertl MG, Lackner HK, Papousek I, Roessler A, Hinghofer-Szalkay H, et al. (2013) Phase Synchronization of Hemodynamic Variables at Rest and after Deep Breathing Measured during the Course of Pregnancy. PLoS ONE 8(4): e60675. doi:10.1371/journal.pone.0060675 Editor: Michael Bader, Max-Delbru ¨ ck Center for Molecular Medicine (MDC), Germany Received November 28, 2012; Accepted March 1, 2013; Published April 5, 2013 Copyright: ß 2013 Moertl et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: The authors did not receive any financial support, but the Task Force MonitorH has been provided by CNSystems Medizintechnik AG, Graz, Austria. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The Task Force MonitorH has been provided by CNSystems Medizintechnik AG. This does not alter the authors’ adherence to all the PLOS ONE policies on sharing data and materials. * E-mail: helmut.lackner@pro.medunigraz.at . These authors contributed equally to this work. Introduction During pregnancy the maternal cardiovascular system (CVS) undergoes profound changes important to assure a normal pregnancy outcome [1–4]. The capacity of cardiovascular regulation to operate effectively under varying conditions depends on the integrity of parasympathetic and sympathetic systems and neurohormonal mechanisms. However the role of the autonomic nervous system (ANS) in the cardiovascular adaptation to pregnancy-related demands is poorly understood [5–7]. The analysis of heart rate variability (HRV), blood pressure variability (BPV), and baroreflex sensitivity (BRS) has become a powerful tool for the assessment of autonomic control [8–10]. In the field of gynecology, these techniques are particularly suitable for pregnant women because virtually non-invasive devices allow studying the profound changes of maternal heart rate (R-R interval), blood pressure (BP) and respiration (RESP) during pregnancy [11–15]. Various mathematical methods have been used with the objective to appropriately describe the cardiovas- cular changes and their mechanisms during gestation [16–23]. PLOS ONE | www.plosone.org 1 April 2013 | Volume 8 | Issue 4 | e60675