Time scales of autonomic information flow in near-term fetal sheep

M G Frasch,B Frank,T Müller,M Last

doi:10.3389/fphys.2012.00378

Abstract

Autonomic information flow (AIF) characterizes fetal heart rate (FHR) variability (fHRV) in the time scale dependent complexity domain and discriminates sleep states [high voltage/low frequency (HV/LF) and low voltage/high frequency (LV/HF) electrocortical activity (ECoG)]. However, the physiologic relationship of AIF time scales to the underlying sympathetic and vagal rhythms is not known. Understanding this relationship will enhance the benefits derived from using fHRV to monitor fetal health non-invasively. We analyzed AIF measured as Kullback–Leibler entropy (KLE) in fetal sheep in late gestation as function of vagal and sympathetic modulation of fHRV, using atropine and propranolol, respectively (n = 6), and also analyzed changes in fHRV during sleep states (n = 12). Atropine blockade resulted in complexity decrease at 2.5 Hz compared to baseline HV/LF and LV/HF states and at 1.6 Hz compared to LV/HF. Propranolol blockade resulted in complexity increase in the 0.8–1 Hz range compared to LV/HF and in no changes when compared to HV/LF. During LV/HF state activity, fHRV complexity was lower at 2.5 Hz and higher at 0.15–0.19 Hz than during HV/LF. Our findings show that in mature fetuses near term vagal activity contributes to fHRV complexity on a wider range of time scales than sympathetic activity. Related to sleep, during LV/HF we found lower complexity at short-term time scale where complexity is also decreased due to vagal blockade. We conclude that vagal and sympathetic modulations of fHRV show sleep state-dependent and time scale-dependent complexity patterns captured by AIF analysis of fHRV. Specifically, we observed a vagally mediated and sleep state-dependent change in these patterns at a time scale around 2.5 Hz (0.2 s). A paradigm of state-dependent non-linear sympathovagal modulation of fHRV is discussed.

Highlights

Autonomic vagal and sympathetic activities in sheep and human fetuses vary with behavioral states and with the health of the fetus
high voltage/low frequency (HV/LF) AND low voltage/high frequency (LV/HF) ELECTROCORTICAL STATE ACTIVITY In 1.8 min long data-sets used to compare effects of atropine/propranolol blockades on fHRV complexity vs. HV/LF and LV/HF sleep states no differences between the sleep states were found
We found that fHRV complexity in LV/HF vs. HV/LF state in 11 out of 12 fetuses was lower at the time scale of 0.2 s (2.5 Hz) and in 10 out of 12 fetuses higher at the time scale 2.7–3.3 s (Frank et al, 2006a,b) (0.15–0.19 Hz) (Figures 3 and 4)

Summary

Introduction

Autonomic vagal and sympathetic activities in sheep and human fetuses vary with behavioral states and with the health of the fetus This has been shown non-invasively in human fetuses and in ovine models of human fetal development by analysis of the fetal heart rate (FHR) variability (fHRV) (Karin et al, 1993; Groome et al, 1994; Metsala et al, 1995; Kimura et al, 1996; Van Leeuwen et al, 2003; Frank et al, 2006a,b; Schneider et al, 2008, 2009; Frasch et al, 2009a,b; Hoyer et al, 2009; Lange et al, 2009; van Laar et al, 2011). Due to the fundamentally nonlinear structure of HRV additional methods are required in order to capture the non-linear fHRV properties, overcoming the methodical limitation of the linear HRV analysis (Groome et al, 1999; Frasch et al, 2009a,b; Hoyer et al, 2011)

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