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      Effect of Hyperventilation on Periodic Repolarization Dynamics

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          Abstract

          Heart and lung functions are closely connected, and the interaction is mediated by the autonomic nervous system. Hyperventilation has been demonstrated to especially activate its sympathetic branch. However, there is still a lack of methods to assess autonomic activity within this cardiorespiratory coupling. Periodic repolarization dynamics (PRD) is an ECG-based biomarker mirroring the effect of efferent cardiac sympathetic activity on the ventricular myocardium. Its calculation is based on beat-to-beat variations of the T wave vector ( dT°). In the present study, we investigated the effects of a standardized hyperventilation maneuver on changes of PRD and its underlying dT° signal in 11 healthy subjects. In response to hyperventilation, dT° revealed a characteristic pattern and normalized dT° values increased significantly compared to baseline [0.063 (IQR 0.032) vs. 0.376 (IQR 0.093), p < 0.001] and recovery [0.082 (IQR 0.029) vs. 0.376 (IQR 0.093), p < 0.001]. During recovery, dT° remained on a higher level compared to baseline ( p = 0.019). When calculating PRD, we found significantly increased PRD values after hyperventilation compared to baseline [3.30 (IQR 2.29) deg 2 vs. 2.76 (IQR 1.43) deg 2, p = 0.018]. Linear regression analysis revealed that the increase in PRD level was independent of heart rate ( p = 0.63). Our pilot data provide further insights in the effect of hyperventilation on sympathetic activity associated repolarization instability.

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          Most cited references24

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          Respiratory sinus arrhythmia: why does the heartbeat synchronize with respiratory rhythm?

          Respiratory sinus arrhythmia (RSA) is heart rate variability in synchrony with respiration, by which the R-R interval on an ECG is shortened during inspiration and prolonged during expiration. Although RSA has been used as an index of cardiac vagal function, it is also a physiologic phenomenon reflecting respiratory-circulatory interactions universally observed among vertebrates. Previous studies have shown that the efficiency of pulmonary gas exchange is improved by RSA, suggesting that RSA may play an active physiologic role. The matched timing of alveolar ventilation and its perfusion with RSA within each respiratory cycle could save energy expenditure by suppressing unnecessary heartbeats during expiration and ineffective ventilation during the ebb of perfusion. Furthermore, evidence has accumulated of a possible dissociation between RSA and vagal control of that heart rate, suggesting differential controls between the respiratory modulation of cardiac vagal outflow and cardiac vagal tone. RSA or heart rate variability in synchrony with respiration is a biological phenomenon, which may have a positive influence on gas exchange at the level of the lung via efficient ventilation/perfusion matching.
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            Hypocapnia.

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              Sympathetic nerve discharge is coupled to muscle cell pH during exercise in humans.

              We used phosphorus nuclear magnetic resonance spectroscopy (31P-NMR) to probe the cellular events in contracting muscle that initiate the reflex stimulation of sympathetic outflow during exercise. In conscious humans, we performed 31P-NMR on exercising forearm muscle and simultaneously recorded muscle sympathetic nerve activity (MSNA) with microelectrodes in the peroneal nerve to determine if the activation of MSNA is coupled to muscle pH, an index of glycolysis, or to the concentrations (II) of inorganic phosphate (Pi) and adenosine diphosphate (ADP) which are modulators of mitochondrial respiration. During both static and rhythmic handgrip, the onset of sympathetic activation in resting muscle coincided with the development of cellular acidification in active muscle. Furthermore, increases in MSNA were correlated closely with decreases in intracellular pH but dissociated from changes in phosphocreatine [( PCr]), [Pi], and [ADP]. The principal new conclusion is that activation of muscle sympathetic outflow during exercise in humans is coupled to the cellular accumulation of protons in contracting muscle.
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                Author and article information

                Contributors
                Journal
                Front Physiol
                Front. Physiol.
                Frontiers in Physiology
                Frontiers Media S.A.
                1664-042X
                18 September 2020
                2020
                : 11
                : 542183
                Affiliations
                [1] 1Medizinische Klinik und Poliklinik I, University Hospital Munich, Ludwig-Maximilians University Munich (LMU) , Munich, Germany
                [2] 2DZHK (German Centre for Cardiovascular Research), Partner Site Munich, Munich Heart Alliance (MHA) , Munich, Germany
                [3] 3Walter Brendel Centre of Experimental Medicine, Ludwig-Maximilians University Munich (LMU) , Munich, Germany
                [4] 4University Hospital for Internal Medicine III, Medical University Innsbruck , Innsbruck, Austria
                Author notes

                Edited by: Tijana Bojić, University of Belgrade, Serbia

                Reviewed by: Michele Orini, University College London, United Kingdom; Evan L. Matthews, Montclair State University, United States

                *Correspondence: Stefan Brunner, stefan.brunner@ 123456med.uni-muenchen.de

                These authors have contributed equally to this work

                This article was submitted to Autonomic Neuroscience, a section of the journal Frontiers in Physiology

                Article
                10.3389/fphys.2020.542183
                7530251
                f3cee811-1fc1-40d3-aa0e-5834746d46bf
                Copyright © 2020 Schüttler, von Stülpnagel, Rizas, Bauer, Brunner and Hamm.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 11 March 2020
                : 27 August 2020
                Page count
                Figures: 3, Tables: 0, Equations: 0, References: 26, Pages: 5, Words: 3680
                Funding
                Funded by: Clinician Scientist Program In Vascular Medicine
                Award ID: MA 2186/14-1
                Categories
                Physiology
                Brief Research Report

                Anatomy & Physiology
                hyperventilation,autonomic function,sympathetic nervous system,repolarization instability,t wave vector,periodic repolarization dynamics

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