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

Abstract

Fetal heart rate variability (FHRV) is a key 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 key mediator of intrapartum FHRV. 26 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 to 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 minutes after a deep intrapartum deceleration, and takes 5-10 minutes to recover. The parasympathetic system is therefore likely to be the key mediator of FHRV once frequent FHR decelerations are established during labor.

Transient effects of forebrain ischemia on fetal heart rate variability in fetal sheep

“…We did not perform any detrending in the present study, and therefore this may reflect the effects of bradycardia and subsequent transition to tachycardia on the mathematical calculation of FHRV. Nonetheless, these findings are also consistent with evidence that the early minutes of both systemic moderate hypoxia and severe asphyxia in fetal sheep is associated with increased FHRV (21,38,39). Thereafter, we observed limited effect of continuing ischemia on measures of FHRV, except for a progressive increase in SampEn, which is a measure of complexity of heart rate ( 40).…”

“…For example, it is broadly believed that the appearance of "normal" FHRV is an expression of an intact central nervous system, requiring essentially all components to be functioning, including the cerebral cortex, midbrain, and medulla as well as the autonomic efferent pathways (15). The contribution of both sympathetic and parasympathetic efferents to FHRV is well established (16)(17)(18)(19)(20)(21), and recently the presence of intrinsic sinoatrial nodal rhythms has been confirmed in the fetus (22). Although it is intuitive that higher centers in the forebrain influence autonomic outflow, and therefore make at least an indirect contribution to FHRV, this has never been systematically tested.…”

Physiological control of fetal heart rate variability during labour: implications and controversies

“…2014; Lear et al . 2016a, 2020a, e), with the intrinsic rhythms of the sinoatrial node (Dalton et al . 1983; Frasch et al .…”

“…This parasympathetic blockade study utilized a short series of three 1 min UCOs repeated every 5 min (Lear et al . 2020e), which is well‐tolerated by healthy fetal sheep. Our finding that the sympathetic contribution was suppressed even during this relatively low frequency of hypoxaemia strongly suggests that parasympathetic activity is the sole mediator of intrapartum FHRV once deep decelerations are present.…”

“…In our study, partial recovery of sympathetic‐mediated FHRV was observed approximately 4–5 min after 1 min UCOs and full recovery by 10 min after the final UCO (Lear et al . 2020e). This time course appears to be more consistent with the half‐life of circulating catecholamines of 2–4 min in fetal sheep (Paulick et al .…”