Ex Utero Extracorporeal Support as a Model for Fetal Hypoxia and Brain Dysmaturity.

Autor: McGovern PE; The Center for Fetal Research, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania., Lawrence K; The Center for Fetal Research, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania., Baumgarten H; The Center for Fetal Research, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania., Rossidis AC; The Center for Fetal Research, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania., Mejaddam AY; The Center for Fetal Research, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania., Licht DJ; Division of Neurology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania., Grinspan J; Division of Neurology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania., Schupper A; The Center for Fetal Research, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania., Rychik J; Division of Cardiology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania., Didier RA; Department of Radiology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania., Vossough A; Department of Radiology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania., Spray TL; Division of Cardiothoracic Surgery, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania., Peranteau WH; The Center for Fetal Research, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania., Davey MG; The Center for Fetal Research, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania., Flake AW; The Center for Fetal Research, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania., Gaynor JW; Division of Cardiothoracic Surgery, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania. Electronic address: gaynor@email.chop.edu.
Jazyk: angličtina
Zdroj: The Annals of thoracic surgery [Ann Thorac Surg] 2020 Mar; Vol. 109 (3), pp. 810-819. Date of Electronic Publication: 2019 Sep 18.
DOI: 10.1016/j.athoracsur.2019.08.021
Abstrakt: Background: Congenital heart disease (CHD) is associated with abnormal fetal brain development, a phenomenon that may be related to decreased cerebral oxygen delivery in utero. We used an artificial womb model to test the hypothesis that decreasing fetal oxygen delivery would reproduce physiologic changes identified in fetuses with CHD.
Methods: Experimental (hypoxemic) fetal lambs (mean gestational age, 111 ± 3 days; n = 4) and control animals (112 days; n = 5) were maintained in the artificial womb for a mean of 22 ± 6 days. Oxygen delivery was reduced to 15.6 ± 1.0 mL/kg/min in the hypoxemia animals versus 21.6 ± 2.0 mL/kg/min in the control animals. Blood chemistry analysis and sonographic evaluation were performed daily. An additional control group (n = 7) was maintained in utero and harvested for analysis at gestational age 134 ± 4 days.
Results: Physiologic variables were monitored continuously, and no statistical differences between the groups were identified. Fetal oxygen delivery and arterial partial pressure of oxygen were remarkably lower in the experimental group longitudinally. Increased umbilical artery and decreased middle cerebral artery resistance resulted in a lower cerebral to umbilical resistance ratio, similar to the brain sparing effect observed in human fetuses with CHD. Experimental brains were smaller than control brains in relation to the calvarium on magnetic resonance.
Conclusions: Sustained hypoxemia in fetal sheep leads to altered cerebrovascular resistances and loss of brain mass, similar to human fetuses with CHD. This unique model provides opportunities to investigate the pathologic process underlying CHD-associated brain dysmaturity and to evaluate potential fetal neuroprotective therapies.
(Copyright © 2020 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE