Beyond the Baroreflex: A New Measure of Autonomic Regulation Based on the Time-Frequency Assessment of Variability, Phase Coherence and Couplings

Philip T Clemson; Jeffrey B Hoag; William H Cooke; Dwain L Eckberg; Aneta Stefanovska

doi:10.3389/fnetp.2022.891604

Beyond the Baroreflex: A New Measure of Autonomic Regulation Based on the Time-Frequency Assessment of Variability, Phase Coherence and Couplings

Front Netw Physiol. 2022 Jun 6:2:891604. doi: 10.3389/fnetp.2022.891604. eCollection 2022.

Authors

Philip T Clemson^{1

2}, Jeffrey B Hoag³, William H Cooke⁴, Dwain L Eckberg^{5

6}, Aneta Stefanovska²

Affiliations

¹ Department of Electrical Engineering and Electronics, University of Liverpool, Liverpool, United Kingdom.
² Physics Department, Lancaster University, Lancaster, United Kingdom.
³ Jane and Leonard Korman Respiratory Institute, Thomas Jefferson University, Philadelphia, PA, United States.
⁴ Kinesiology and Integrative Physiology Department, Michigan Technological University, Houghton, MI, United States.
⁵ Departments of Medicine and Physiology, Virginia Commonwealth University School of Medicine, Richmond, VA, United States.
⁶ Department of Veterans Affairs Medical Center, Richmond, VA, United States.

Abstract

For decades the role of autonomic regulation and the baroreflex in the generation of the respiratory sinus arrhythmia (RSA) - modulation of heart rate by the frequency of breathing - has been under dispute. We hypothesized that by using autonomic blockers we can reveal which oscillations and their interactions are suppressed, elucidating their involvement in RSA as well as in cardiovascular regulation more generally. R-R intervals, end tidal CO₂, finger arterial pressure, and muscle sympathetic nerve activity (MSNA) were measured simultaneously in 7 subjects during saline, atropine and propranolol infusion. The measurements were repeated during spontaneous and fixed-frequency breathing, and apnea. The power spectra, phase coherence and couplings were calculated to characterise the variability and interactions within the cardiovascular system. Atropine reduced R-R interval variability (p < 0.05) in all three breathing conditions, reduced MSNA power during apnea and removed much of the significant coherence and couplings. Propranolol had smaller effect on the power of oscillations and did not change the number of significant interactions. Most notably, atropine reduced R-R interval power in the 0.145-0.6 Hz interval during apnea, which supports the hypothesis that the RSA is modulated by a mechanism other than the baroreflex. Atropine also reduced or made negative the phase shift between the systolic and diastolic pressure, indicating the cessation of baroreflex-dependent blood pressure variability. This result suggests that coherent respiratory oscillations in the blood pressure can be used for the non-invasive assessment of autonomic regulation.

Keywords: atropine; baroreflex; phase shift; propranolol; wavelet phase coherence.

Grants and funding

The research was supported by the Engineering and Physical Sciences Research Council (Grants No. EP/M006298/1 and No EP/100999X1), Action Medical Research (Grant No. GN 1963), the Slovenian Research Agency (Program No. P20232), the Innovative Training Network COSMOS program (funded by the EU Horizon 2020 research and innovation program under the Marie Sklodowska-Curie Grant Agreement No. 642563), and by a Royal Society International Short Visit Grant.