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

Fetal heart rate (FHR) variability (FHRV) and ST segment morphology are potential clinical indices of fetal well-being during labor. β-Adrenergic stimulation by circulating catecholamines has been hypothesized to contribute to both FHRV and ST segment morphology during labor, but this has not been tested during brief repeated fetal hypoxemia that is characteristic of labor. Near-term fetal sheep (0.85 gestation) received propranolol (β-adrenergic blockade; n = 10) or saline ( n = 7) 30 min before being exposed to three 2-min complete umbilical cord occlusions (UCOs) separated by 3-min reperfusions. T/QRS ratio was calculated throughout UCOs and reperfusion periods, and measures of FHRV (RMSSD, SDNN, and STV) were calculated between UCOs. During the baseline period, before the start of UCOs, propranolol was associated with reduced FHR, SDNN, and STV but did not affect RMSSD or T/QRS ratio. UCOs were associated with rapid FHR decelerations and increased T/QRS ratio; propranolol significantly reduced FHR during UCOs and was associated with a slower rise in T/QRS ratio during the first UCOs, without affecting the maximal rise or T/QRS ratio during the second and third UCO. Between UCOs propranolol reduced FHR and T/QRS ratio but did not affect any measure of FHRV. These data demonstrate that circulating catecholamines do not contribute to FHRV during labor-like hypoxemia. Furthermore, circulating catecholamines did not contribute to the major rise in T/QRS ratio during labor-like hypoxemia but may regulate T/QRS ratio between brief hypoxemia.

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Parasympathetic activity is the key regulator of heart rate variability between decelerations during brief repeated umbilical cord occlusions in fetal sheep

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00186.2020 ◽

2020 ◽

Vol 319 (5) ◽

pp. R541-R550

Author(s):

Christopher A. Lear ◽

Jenny A. Westgate ◽

Michi Kasai ◽

Michael J. Beacom ◽

Yoshiki Maeda ◽

...

Keyword(s):

Heart Rate ◽

Heart Rate Variability ◽

Umbilical Cord ◽

Well Being ◽

Atropine Sulfate ◽

Control Group ◽

Fetal Sheep ◽

Uterine Contractions ◽

Parasympathetic System ◽

Cervical Vagotomy

Fetal heart rate variability (FHRV) is a widely used index of intrapartum well being. Both arms of the autonomic system regulate FHRV under normoxic conditions in the antenatal period. However, autonomic control of FHRV during labor when the fetus is exposed to repeated, brief hypoxemia during uterine contractions is poorly understood. We have previously shown that the sympathetic nervous system (SNS) does not regulate FHRV during labor-like hypoxia. We therefore investigated the hypothesis that the parasympathetic system is the main mediator of intrapartum FHRV. Twenty-six chronically instrumented fetal sheep at 0.85 of gestation received either bilateral cervical vagotomy ( n = 7), atropine sulfate ( n = 7), or sham treatment (control, n = 12), followed by three 1-min complete umbilical cord occlusions (UCOs) separated by 4-min reperfusion periods. Parasympathetic blockade reduced three measures of FHRV before UCOs (all P < 0.01). Between UCOs, atropine and vagotomy were associated with marked tachycardia (both P < 0.005), suppressed measures of FHRV (all P < 0.01), and abolished FHRV on visual inspection compared with the control group. Tachycardia in the atropine and vagotomy groups resolved over the first 10 min after the final UCO, in association with evidence that the SNS contribution to FHRV progressively returned during this time. Our findings support that SNS control of FHRV is acutely suppressed for at least 4 min after a deep intrapartum deceleration and takes 5–10 min to recover. The parasympathetic system is therefore likely to be the key mediator of FHRV once frequent FHR decelerations are established during labor.

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Peripheral chemoreflex control of fetal heart rate decelerations overwhelms the baroreflex during brief umbilical cord occlusions in fetal sheep

The Journal of Physiology ◽

10.1113/jp279573 ◽

2020 ◽

Vol 598 (20) ◽

pp. 4523-4536 ◽

Cited By ~ 5

Author(s):

Christopher A. Lear ◽

Michi Kasai ◽

Lindsea C. Booth ◽

Paul P. Drury ◽

Joanne O. Davidson ◽

...

Keyword(s):

Heart Rate ◽

Umbilical Cord ◽

Fetal Heart Rate ◽

Fetal Heart ◽

Fetal Sheep ◽

Peripheral Chemoreflex

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Does heart rate variability reflect the systemic inflammatory response in a fetal sheep model of lipopolysaccharide-induced sepsis?

Physiological Measurement ◽

10.1088/0967-3334/36/10/2089 ◽

2015 ◽

Vol 36 (10) ◽

pp. 2089-2102 ◽

Cited By ~ 28

Author(s):

Lucien D Durosier ◽

Christophe L Herry ◽

Marina Cortes ◽

Mingju Cao ◽

Patrick Burns ◽

...

Keyword(s):

Heart Rate ◽

Heart Rate Variability ◽

Inflammatory Response ◽

Systemic Inflammatory Response ◽

Sheep Model ◽

Fetal Sheep

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A new analysis of heart rate variability in the assessment of fetal parasympathetic activity: An experimental study in a fetal sheep model

PLoS ONE ◽

10.1371/journal.pone.0180653 ◽

2017 ◽

Vol 12 (7) ◽

pp. e0180653 ◽

Cited By ~ 11

Author(s):

C. Garabedian ◽

C. Champion ◽

E. Servan-Schreiber ◽

L. Butruille ◽

E. Aubry ◽

...

Keyword(s):

Heart Rate ◽

Experimental Study ◽

Heart Rate Variability ◽

Parasympathetic Activity ◽

Sheep Model ◽

Fetal Sheep

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Validation of spontaneous assessment of baroreceptor reflex sensitivity and its relation to heart rate variability in the ovine fetus pre- and near-term

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y09-070 ◽

2009 ◽

Vol 87 (9) ◽

pp. 736-742 ◽

Cited By ~ 3

Author(s):

Martin G. Frasch ◽

Thomas Müller ◽

Mark Szynkaruk ◽

Matthias Schwab

Keyword(s):

Heart Rate ◽

Heart Rate Variability ◽

Reference Method ◽

Baroreceptor Reflex ◽

Vasoactive Drugs ◽

Sequence Method ◽

Baroreceptor Reflex Sensitivity ◽

Ovine Fetus ◽

Fetal Heart Rate Variability ◽

Near Term

Assessment of baroreceptor reflex sensitivity (BRS) in the ovine fetus provides insight into autonomic cardiovascular regulation. Currently, assessment of BRS relies on vasoactive drugs, but this approach is limited by feasibility issues and by the nonphysiologic nature of the stimulus. Thus we aimed to validate the method of spontaneous BRS assessment against the reference method of using vasoactive drugs in preterm (0.76 gestation, n = 16) and near-term (0.86 gestation, n = 16) chronically instrumented ovine fetuses. The BRS measures derived from the spontaneous and reference methods correlated at both gestational ages (R = 0.67 ± 0.03). The sequence method of spontaneous BRS measures also correlated both to the root mean square of standard deviations (RMSSD), which is a measure of fetal heart rate variability reflecting vagal modulation (R = 0.69 ± 0.03), and to fetal body weight (R = 0.65 ± 0.03), which is a surrogate for growth trajectory of each fetus. The methodology presented may aid in developing new models to study BRS and cardiovascular control in ovine fetus in the last trimester of pregnancy.

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Fetal arterial pressure and heart rate changes in surviving and non-surviving immature fetal sheep following brief repeated total umbilical cord occlusions

European Journal of Obstetrics & Gynecology and Reproductive Biology ◽

10.1016/s0301-2115(99)00098-6 ◽

1999 ◽

Vol 87 (2) ◽

pp. 151-157 ◽

Cited By ~ 7

Author(s):

Han Keunen ◽

Tom H.M. Hasaart

Keyword(s):

Heart Rate ◽

Arterial Pressure ◽

Umbilical Cord ◽

Fetal Sheep

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Biphasic changes in fetal heart rate variability in preterm fetal sheep developing hypotension after acute on chronic lipopolysaccharide exposure

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00110.2014 ◽

2014 ◽

Vol 307 (4) ◽

pp. R387-R395 ◽

Cited By ~ 8

Author(s):

Christopher A. Lear ◽

Joanne O. Davidson ◽

Lindsea C. Booth ◽

Guido Wassink ◽

Robert Galinsky ◽

...

Keyword(s):

Heart Rate ◽

Heart Rate Variability ◽

Fetal Heart Rate ◽

Low Dose ◽

Fetal Heart ◽

Transient Increase ◽

Electromyographic Activity ◽

Fetal Sheep ◽

Arterial Blood ◽

Fetal Heart Rate Variability

Perinatal exposure to infection is highly associated with adverse outcomes. Experimentally, acute, severe exposure to gram-negative bacterial lipopolysaccharide (LPS) is associated with increased fetal heart rate variability (FHRV). It is unknown whether FHRV is affected by subclinical infection with or without acute exacerbations. We therefore tested the hypothesis that FHRV would be associated with hypotension after acute on chronic exposure to LPS. Chronically instrumented fetal sheep at 0.7 gestation were exposed to a continuous low-dose LPS infusion ( n = 12, 100 ng/kg over 24 h, followed by 250 ng·kg−1·24 h−1 for a further 96 h) or the same volume of saline ( n = 10). Boluses of either 1 μg LPS or saline were given at 48, 72, and 96 h. Low-dose infusion was not associated with hemodynamic or FHRV changes. The first LPS bolus was associated with tachycardia and suppression of nuchal electromyographic activity in all fetuses. Seven of twelve fetuses developed hypotension (a fall in mean arterial blood pressure ≥5 mmHg). FHRV was transiently increased only at the onset of hypotension, in association with increased cytokine induction and electroencephalogram suppression. FHRV then fell before the nadir of hypotension, with transient suppression of short-term FHRV. After the second LPS bolus, the hypotension group showed a biphasic pattern of a transient increase in FHRV followed by more prolonged suppression. These findings suggest that infection-related hypotension in the preterm fetus mediates the transient increase in FHRV and that repeated exposure to LPS leads to progressive loss of FHRV.

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