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

Abstract

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.

Impact of Chronic Fetal Hypoxia and Inflammation on Cardiac Pacemaker Cell Development

“…[3,34,35] Our recent data suggest that fetal intrinsic beat-to-beat HRV is present in the healthy fetus near-term and shows a memory of previous exposure to chronic hypoxia. [36] The two-clock coupling mechanism discussed in section 1 [10] may provide at least a partial explanation for this memory to chronic hypoxic conditions which, in addition to lowering energy availability, is known to program sympathetic hyperactivity in the offspring. [36][37][38]…”

“…[36] The two-clock coupling mechanism discussed in section 1 [10] may provide at least a partial explanation for this memory to chronic hypoxic conditions which, in addition to lowering energy availability, is known to program sympathetic hyperactivity in the offspring. [36][37][38]…”

“…We have recently discovered that iHRV originates in fetal life and that chronic fetal hypoxia significantly alters it. [36] Interestingly, iHRV and its memory of chronic fetal hypoxia are characterized by nonlinear properties reflecting its recurrent state and chaotic behavior;…”

“…This opens a multitude of questions regarding the clinical application, which we list below in the hope that they will inspire future investigations: a) Are there suitable HRV properties likely to capture iHRV in vivo? In [36] we report such putative HRV measures representing recurrent states, chaotic and fractal dynamics. We invite the interested reader to explore this study and test the identified measurable d) The HRV code has been proposed as an overarching concept incorporating the various multi-scale contributions of inter-organ communication reflected in HRV.…”

#29 Heart rate variability monitoring identifies asymptomatic toddlers exposed to Zika virus during pregnancy

“…. The discriminating HRV measure Grid Count (gcount) is shown in hypoxic versus normoxic (both in-vivo and ex-vivo) near-term ovine fetuses (presented elsewhere 15,16 ) and ZIKV-exposed versus control human cohorts. The rationale for this juxtaposition is the purported chronic hypoxic effect of ZIKV exposure on fetal development.…”