Ontogeny and control of the heart rate power spectrum in the last third of gestation in fetal sheep

Abstract

New Findings r What is the central question of this study? Can power spectral analysis of fetal heart rate variability provide a reliable, objective estimate of autonomic balance before birth? r What is the main finding and its importance? This study demonstrates that there is a substantial increase in fetal heart rate spectral power over late gestation in chronically instrumented fetal sheep, with changes between sleep states that are consistent with known patterns of autonomic activity. However, parasympathetic blockade with atropine and complete chemical sympathectomy did not support substantial, consistent differences in the frequencies of sympathetic and parasympathetic activity in late gestation, suggesting that this does not provide a reliable index of relative cardiac autonomic activity before birth. Power spectral analysis of fetal heart rate variability has been proposed to provide a non-invasive estimate of autonomic balance. However, there are few systematic data before birth. We therefore examined developmental changes in the frequency power spectrum at very low (0-0.04 Hz), low (0.04-0.15 Hz) and high frequencies (0.15-0.4 Hz), as well as the ratio of low-to high-frequency power (LF/HF), in chronically catheterized, healthy fetal sheep at 0.6 (n = 8), 0.7 (n = 7) and 0.8 gestational age (ga; n = 11). In a second study, 0.8 ga fetuses received either atropine (4.8 mg bolus, then 4.8 mg h −1 for 30 min, n = 6) or 6-hydroxydopamine (20 mg ml −1 at 2.5 ml h −1 for 3 h; n = 9). Data were analysed by sleep state, defined by low-voltage-high-frequency (LV) or high-voltage-low-frequency (HV) EEG. Total spectral power increased with gestational age (P < 0.05), while LF/HF decreased from 0.6 to 0.7 ga. At 0.8 ga, heart rate and LF/HF were significantly higher during HV than LV sleep (P < 0.05). Consistent with this, although total spectral power was not significantly greater during HV sleep, there was a significant interaction between sleep state and frequency band (P = 0.02). Both atropine (P = 0.05) and 6-hydroxydopamine (P < 0.05) were associated with an overall reduction in spectral power but no significant effect on the LF/HF ratio. This study does not support substantial, consistent differences between the frequencies of sympathetic and parasympathetic activity in late-gestation fetal sheep.

Sympathetic neural activation does not mediate heart rate variability during repeated brief umbilical cord occlusions in near‐term fetal sheep

“…These contrasting results may in part reflect evidence from near‐term fetal sheep that both the sympathetic and parasympathetic systems contribute to low frequency FHRV, probably preventing low frequency activity from being a reliable measure of sympathetic activity (Koome et al . ). Moreover, changes in normalised as opposed to absolute low frequency activity may be due to changes in total FHRV.…”

“…This probably partly explains why both sympathectomy and parasympathetic blockade in fetal sheep were associated with significant reductions in overall spectral power, without significantly changing the distribution of spectral power (Koome et al . ). Thus, although RMSSD appeared to provide a robust measure of parasympathetic‐mediated FHRV in the present study, this should not be taken to mean that it would provide a reliable, direct measure of parasympathetic activity under all situations.…”

“…Again, this is consistent with the proposal that there is considerable overlap between the frequency of sympathetic and parasympathetic activity before birth (Koome et al . ).…”

Early sinusoidal heart rate patterns and heart rate variability to assess hypoxia–ischaemia in near‐term fetal sheep

“…; Koome et al . ; Lear et al . ), and so changes in HRV may provide information on the timing and severity of HI injury.…”

Regularity of Fetal HRV Changes in an In:vivo Sheep Model of Labor

“…Such mechanisms are part of a complex interaction that involves several input signals such as chemoreceptor, baroreceptor and others. However, it is difficult to determine the exact interaction using standard heart rate variability analysis because of the high variability of its estimates [4]. In the context of heart rate variability analysis, signals' regularity has been quantified by means of many different entropy metrics.…”