Altered autonomic control of heart rate variability in the chronically hypoxic fetus

Shaw, CJ; Allison, Beth J.; Itani, Nozomi; Botting, Kimberley J.; Niu, Youguo; Lees, C.; Giussani, Dino A.

doi:10.1113/jp275659

Cited by 32 publications

(38 citation statements)

References 48 publications

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“…Interestingly, in the ex vivo measurements, the values for fetal heart rate were not significantly different. Basal heart rate may influence the degree of HRV, but, at least based on our ex vivo observations, that was not a confounding factor in the present study (Monfredi et al 2014;Shaw et al 2018).…”

Section: Study Limitationsmentioning

confidence: 63%

“…Briefly, chronically catheterized ewes carrying male singleton fetuses were exposed to normoxia (n = 6) or hypoxia (10% inspired O 2 , n = 9) for the last third of gestation (105-138 days of gestation (dG); term ß145 dG) in bespoke isobaric chambers (Brain et al 2015;Allison et al 2016;Shaw et al 2018) (Figs 1 and 2). At 138 dG, isolated hearts were studied under a Langendorff preparation using established techniques (Fletcher et al 2005;Niu et al 2013Niu et al , 2018 (Fig.…”

Section: Surgical Preparationmentioning

confidence: 99%

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First evidence that intrinsic fetal heart rate variability exists and is affected by hypoxic pregnancy

Frasch

Herry

Niu

et al. 2018

Preprint

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Heart rate variability (HRV) is an important indicator of health and disease, yet its physiological origins are poorly understood. The contribution of intrinsic and extrinsic sources to HRV is not known. In a near-term fetal sheep model, we aimed to identify fetal HRV measures reflecting intrinsic contributions to HRV. Ex vivo Langendorff preparation was used to record intrinsic HRV in animals who were normoxic or hypoxic in vivo. We identify the intrinsic HRV in isolated hearts from fetal sheep in late gestation and how it is affected by chronic fetal hypoxia. Significance StatementHeart rate variability (HRV) is an important indicator of health and disease, yet its physiological origins are poorly understood. Both, the heart, intrinsically, and extrinsic systems, such as the brain, are hypothesized to contribute to HRV. In a near-term fetal sheep model of human development, we identified fetal HRV components reflecting intrinsic contributions to HRV. In addition, we show that these intrinsic HRV components carry memory of chronic oxygen deprivation the fetus experienced during the last third of gestation.peer-reviewed) is the author/funder. All rights reserved. No reuse allowed without permission.The copyright holder for this preprint (which was not . http://dx.doi.org/10.1101/242107 doi: bioRxiv preprint first posted online Jan. 22, 2018; 3 IntroductionFetal heart rate (FHR) monitoring is widely used clinically during labour, although its ability to identify fetuses at risk of severe metabolic acidosis is poor.(1) It is established that normal FHR variability (fHRV) represents a complex, nonlinear integration of the sympathetic and parasympathetic nervous system activities. Fetal body and breathing movements, baroreflex and circadian processes also influence HRV.(2,3,4-6) There is also some evidence that intrinsic pacemaker rhythms of the sino-atrial node affect HRV in critically ill adults. (7) However, whether intrinsic HRV (iHRV) exists in the fetal period and whether this is affected by chronic fetal hypoxia has never been tested. Here, we show iHRV in isolated hearts from fetal sheep in late gestation. We also show that chronic fetal hypoxia has significant effects on iHRV.

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Section: Study Limitationsmentioning

confidence: 63%

Section: Surgical Preparationmentioning

confidence: 99%

First evidence that intrinsic fetal heart rate variability exists and is affected by hypoxic pregnancy

Frasch

Herry

Niu

et al. 2018

Preprint

Self Cite

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“…; Shaw et al . ) (Figs and ). At 138 dG, isolated hearts were studied under a Langendorff preparation using established techniques (Fletcher et al .…”

Section: Methodsmentioning

confidence: 84%

First evidence that intrinsic fetal heart rate variability exists and is affected by hypoxic pregnancy

Frasch

Herry

Niu

et al. 2020

The Journal of Physiology

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Key points We introduce a technique to test whether intrinsic fetal heart rate variability (iFHRV) exists and we show the utility of the technique by testing the hypothesis that iFHRV is affected by chronic fetal hypoxia, one of the most common adverse outcomes of human pregnancy complicated by fetal growth restriction. Using an established late gestation ovine model of fetal development under chronic hypoxic conditions, we identify iFHRV in isolated fetal hearts and show that it is markedly affected by hypoxic pregnancy. Therefore, the isolated fetal heart has intrinsic variability and carries a memory of adverse intrauterine conditions experienced during the last third of pregnancy. Abstract Fetal heart rate variability (FHRV) emerges from influences of the autonomic nervous system, fetal body and breathing movements, and from baroreflex and circadian processes. We tested whether intrinsic heart rate variability (iHRV), devoid of any external influences, exists in the fetal period and whether it is affected by chronic fetal hypoxia. Chronically catheterized ewes carrying male singleton fetuses were exposed to normoxia (n = 6) or hypoxia (10% inspired O2, n = 9) for the last third of gestation (105–138 days of gestation (dG); term ∼145 dG) in isobaric chambers. At 138 dG, isolated hearts were studied using a Langendorff preparation. We calculated basal intrinsic FHRV (iFHRV) indices reflecting iFHRV's variability, predictability, temporal symmetry, fractality and chaotic behaviour, from the systolic peaks within 15 min segments in each heart. Significance was assumed at P < 0.05. Hearts of fetuses isolated from hypoxic pregnancy showed approximately 4‐fold increases in the Grid transformation as well as the AND similarity index (sgridAND) and a 4‐fold reduction in the scale‐dependent Lyapunov exponent slope. We also detected a 2‐fold reduction in the Recurrence quantification analysis, percentage of laminarity (pL) and recurrences, maximum and average diagonal line (dlmax, dlmean) and the Multiscale time irreversibility asymmetry index. The iHRV measures dlmax, dlmean, pL and sgridAND correlated with left ventricular end‐diastolic pressure across both groups (average R2 = 0.38 ± 0.03). This is the first evidence that iHRV originates in fetal life and that chronic fetal hypoxia significantly alters it. Isolated fetal hearts from hypoxic pregnancy exhibit a time scale‐dependent higher complexity in iFHRV.

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“…Frequency domain measures of FHRV were calculated by using a power spectrum density estimate, using fast Fourier transformation. The frequency band boundaries used in this study were: very low frequency (VLF), 0-0.04 Hz; low frequency (LF), 0.04-0.15 Hz; and high frequency (HF), 0.15-0.4 Hz Shaw et al 2018). The power of each frequency band was calculated as the natural logarithm of the amplitude.…”

Section: Discussionmentioning

confidence: 99%

“…; Shaw et al . ). The power of each frequency band was calculated as the natural logarithm of the amplitude.…”

Section: Methodsmentioning

confidence: 97%

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

Kasai

Lear

Davidson

et al. 2019

The Journal of Physiology

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Key points •Therapeutic hypothermia needs to be started as early as possible in the first 6 h after acute injury caused by hypoxia–ischaemia (HI), but the severity and timing of HI are often unclear. In this study we evaluated whether measures of heart rate variability (HRV) might provide early biomarkers of HI. •The duration but not magnitude of suppression of HRV power and conversely increased sample entropy of the heart rate were associated with severity of HI, such that changes in the first 3 h did not discriminate between groups. •Relative changes in HRV power bands showed different patterns between groups and therefore may have the potential to evaluate the severity of HI. •Aberrant fetal heart rate patterns and increased arginine vasopressin levels in the first hour after moderate and severe HI were correlated with loss of EEG power after 3 days’ recovery, suggesting potential utility as early biomarkers of outcome. Abstract Therapeutic hypothermia is partially neuroprotective after acute injury caused by hypoxia–ischaemia (HI), likely because the timing and severity of HI are often unclear, making timely recruitment for treatment challenging. We evaluated the utility of changes in heart rate variability (HRV) after HI as biomarkers of the timing and severity of acute HI. Chronically instrumented fetal sheep at 0.85 gestational age were exposed to different durations of umbilical cord occlusion to produce mild (n = 6), moderate (n = 8) or severe HI (n = 8) or to sham occlusion (n = 5). Heart rate (HR) and HRV indices were assessed until 72 h after HI. All HI groups showed suppressed very low frequency HRV power and elevated sample entropy for the first 3 h; more prolonged changes were associated with greater severity of HI. Analysis of relative changes in spectral power showed that the moderate and severe groups showed a shift towards higher HRV frequencies, which was most marked after severe HI. This shift was associated with abnormal rhythmic HR patterns including sinusoidal patterns in the first hour after HI, and with elevated plasma levels of arginine vasopressin, which were correlated with subsequent loss of EEG power by day 3. In conclusion, absolute changes in HRV power in the first 3 h after acute HI were not significantly related to the severity of HI. The intriguing relative shift in spectral power towards higher frequencies likely reflects greater autonomic dysfunction after severe HI. However, sinusoidal HR patterns and elevated vasopressin levels may have utility as biomarkers of severe HI.

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Altered autonomic control of heart rate variability in the chronically hypoxic fetus

Cited by 32 publications

References 48 publications

First evidence that intrinsic fetal heart rate variability exists and is affected by hypoxic pregnancy

First evidence that intrinsic fetal heart rate variability exists and is affected by hypoxic pregnancy

First evidence that intrinsic fetal heart rate variability exists and is affected by hypoxic pregnancy

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

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