Neonatal heart transplantation

John, Mohan M.; Bailey, Leonard L.

doi:10.21037/acs.2018.01.05

Cited by 35 publications

(37 citation statements)

References 30 publications

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“…), the present findings must be validated in human cohorts. This could be performed in the context of human heart transplants, which will likely require a multi‐site effort, because it is rare, with ∼10 transplants performed in the US per year (John & Bailey, ).…”

Section: Discussionmentioning

confidence: 99%

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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Section: Discussionmentioning

confidence: 99%

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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show abstract

“…Albeit derived in one of the most appropriate animal species that shares similar temporal profiles of cardiovascular development to humans (Morrison et al 2018), the present findings must be validated in human cohorts. This could be performed in the context of human heart transplants, which will likely require a multi-site effort, because it is rare, with ß10 transplants performed in the US per year (John & Bailey, 2018).…”

Section: Study Limitationsmentioning

confidence: 99%

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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“…Others report that primary neonatal heart transplantation has a wait list mortality as great as 34%. 3 With operative mortality being reported around 10%, it is hard to champion primary heart transplantation as drastically superior when more than 40% of patients die before or shortly after transplantation. 4 Even if transplantation were clearly better, the problem of donor organ shortage persists.…”

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confidence: 99%