Global and Transient Effects of Intermittent Hypoxia on Heart Rate Variability Markers: Evaluation Using an Obstructive Sleep Apnea Model

Daniel Romero,Raimon Jane

doi:10.1109/access.2021.3053310

Abstract

Intermittent hypoxia (IH) produces autonomic dysfunction that promotes the development of arrhythmia and hypertension in patients with obstructive sleep apnea (OSA). This paper investigated different heart rate variability (HRV) indices in the context of IH using a rat model for OSA. Linear and non-linear HRV parameters were assessed from ultra-short (15-s segments) and short-term (5 min) analyses of heartbeat time-series. Transient changes observed from pre-apnea segments to hypoxia episodes were evaluated, besides the relative and global impact of IH, as a function of its severity. Results showed an overall increase in ultra-short HRV markers as immediate response to hypoxia: standard deviation of normal RR intervals, SDNN = 1.2 ms (IQR: 1.1-2.1) vs 1.4 ms (IQR: 1.2-2.2), p = 0.015; root mean square of the successive differences, RMSSD = 1.7 ms (IQR: 1.5-2.2) vs 1.9 ms (IQR: 1.6-2.4), p = 0.031. The power in the very low frequency (VLF) band also showed a significant increase: 0.09 ms <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> (IQR: 0.05-0.20) vs 0.16 ms <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> (IQR: 0.12-0.23), p = 0.016, probably associated with the potentiation of the carotid body chemo-sensory response to hypoxia. Moreover, a clear link between severity of IH and short-term HRV measures was found in VLF and LF power, besides their progressive increase seen throughout the experiment after each apnea sequence. However, only those markers quantifying fragmentation levels in RR series were significantly affected when the experiment ended, as compared to baseline measures: percentage of inflection points, PIP = 49% (IQR: 45-51) vs 53% (IQR: 47-53), p = 0.031; percentage of short (geq 3 RR intervals) accelerated/decelerated segments, PSS = 75% (IQR: 51-81) vs 87% (IQR: 51-90), p = 0.046. These findings suggest a significant deterioration of cardiac rhythm with a more erratic behavior beyond the normal sinus arrhythmia, that may lead to a future cardiac condition.

Highlights

Obstructive sleep apnea (OSA) is a chronic health condition characterized by repeated apnea episodes during patients’s sleep, resulting in sustained exposure to intermittent hypoxiaThe associate editor coordinating the review of this manuscript and approving it for publication was Wei Wang .(IH), large negative intrathoracic pressure, and arousals
The overall behavior of the markers presented indicates a transient increase in heart rate variability (HRV) before and during apnea episodes, reflected in greater SDNN (1.2 (IQR: 1.1-2.1) vs 1.4 (IQR: 1.2-2.2) ms, p = 0.0156) and RMSSD (1.7 (IQR: 1.5-2.2) vs 1.9 (IQR: 1.6-2.4) ms, p = 0.0312) values, as well as a slight increase in the average cardiac period given by the mean RR values, (IQR: 156-166) vs (IQR: 157-167) ms, p = 0.0156
In this study, we evaluated a set of HRV markers, including temporal and frequency domain parameters, as well as measures to estimate the level of fragmentation in heartbeat time series

Summary

Introduction

Obstructive sleep apnea (OSA) is a chronic health condition characterized by repeated apnea episodes during patients’s sleep, resulting in sustained exposure to intermittent hypoxia. (IH), large negative intrathoracic pressure, and arousals. This chronic condition has been extensively associated with several cardiovascular consequences, such as systemic hypertension, heart failure, coronary artery disease, arrhythmias and stroke [1]–[4]. The underlying mechanisms linking IH to cardiovascular diseases in OSA patients remain unclear, it has been suggested that an elevated sympathetic tone of the autonomic nervous system (ANS) [5], oxidative. Jané: Global and Transient Effects of Intermittent Hypoxia on HRV Markers stress and endothelial dysfunction [2], [6], inflammation, and atherosclerosis [3], [7] may be contributing factors

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