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      Heart rate variability in patients being treated for dengue viral infection: new insights from mathematical correction of heart rate


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          Introduction: Severe dengue hemorrhagic fever (DHF) is a viral infection that acts to increase permeability of capillaries, resulting in internal hemorrhage. Linear frequency domain Fourier spectral analysis represents the most published noninvasive tool for diagnosing and assessing health status via calculated heart rate variability (HRV). As such, HRV may be useful in assessing clinical status in DHF patients, but is prone to erroneous results and conclusions due to the influence of the average HR during the time period of HRV assessment (defined as the “prevailing” HR). We tested the hypothesis that alterations in HRV calculated with linear frequency analysis would be minimal when mathematically corrected for prevailing HR following dengue viral infection.

          Methods: Male ( N = 16) and female ( N = 11) patients between the ages of 6 months and 15 years of age (10 ± 6 SD years) were tracked through the progression of the dengue viral infection with treatment following the abatement of a fever (defervescence). Electrocardiographic recordings were collected and analyzed for HRV.

          Results: High frequency (HF), low frequency (LF), and LF/HF ratio were unaffected by correction for prevailing HR.

          Conclusion: HRV corrected for changes in HR did not alter the interpretation of our data. Therefore, we conclude that cardiac parasympathetic activity (based on HF frequency) is responsible for the majority of the HR reduction following defervescence in patients with dengue viral infection.

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          Most cited references27

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          Observations related to pathogenesis of dengue hemorrhagic fever. IV. Relation of disease severity to antibody response and virus recovered.

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            Sympathovagal balance: a critical appraisal.

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              The effect of heart rate on the heart rate variability response to autonomic interventions

              Heart rate variability (HRV), the beat-to-beat variation in either heart rate (HR) or heart period (R-R interval), has become a popular clinical and investigational tool to quantify cardiac autonomic regulation. However, it is not widely appreciated that, due to the inverse curvilinear relationship between HR and R-R interval, HR per se can profoundly influence HRV. It is, therefore, critical to correct HRV for the prevailing HR particularly, as HR changes in response to autonomic neural activation or inhibition. The present study evaluated the effects of HR on the HRV response to autonomic interventions that either increased (submaximal exercise, n = 25 or baroreceptor reflex activation, n = 20) or reduced (pharmacological blockade: β-adrenergic receptor, muscarinic receptor antagonists alone and in combination, n = 25, or bilateral cervical vagotomy, n = 9) autonomic neural activity in a canine model. Both total (RR interval standard deviation, RRSD) and the high frequency (HF) variability (HF, 0.24–1.04 Hz) were determined before and in response to an autonomic intervention. All interventions that reduced or abolished cardiac parasympathetic regulation provoked large reductions in HRV even after HR correction [division by mean RRsec or (mean RRsec)2 for RRSD and HF, respectively] while interventions that reduced HR yielded mixed results. β-adrenergic receptor blockade reduced HRV (RRSD but not HF) while both RRSD and HF increased in response to increases in arterial blood (baroreceptor reflex activation) even after HR correction. These data suggest that the physiological basis for HRV is revealed after correction for prevailing HR and, further, that cardiac parasympathetic activity is responsible for a major portion of the HRV in the dog.

                Author and article information

                Front Physiol
                Front Physiol
                Front. Physiol.
                Frontiers in Physiology
                Frontiers Media S.A.
                25 February 2014
                : 5
                : 46
                U.S. Army Institute of Surgical Research Fort Sam Houston, TX, USA
                Author notes

                Edited by: Jerzy Sacha, Regional Medical Center in Opole, Poland

                Reviewed by: George E. Billman, The Ohio State University, USA; Jerzy Sacha, Regional Medical Center, Poland

                *Correspondence: Robert Carter III, Research Division, US Army Institute of Surgical Research, 3698 Chambers Pass, JBSA Fort Sam Houston, TX 78234, USA e-mail: robert.carter422.mil@ 123456mail.mil

                This article was submitted to Clinical and Translational Physiology, a section of the journal Frontiers in Physiology.

                Copyright © 2014 Carter, Hinojosa-Laborde and Convertino.

                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) or licensor 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.

                : 20 December 2013
                : 24 January 2014
                Page count
                Figures: 0, Tables: 2, Equations: 0, References: 32, Pages: 4, Words: 3957
                Original Research Article

                Anatomy & Physiology
                dengue hemorrhagic fever,heart rate variability,high power frequency,parasympathetic nervous system,autonomic balance


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