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An Artificial Placenta Protects Against Lung Injury and Promotes Continued Lung Development in Extremely Premature Lambs

Coughlin, Megan A.*; Werner, Nicole L.*; Church, Joseph T.*; Perkins, Elena M.*; Bryner, Benjamin S.*; Barks, John D.; Bentley, John K.; Hershenson, Marc B.†,‡; Rabah, Raja§; Bartlett, Robert H.*; Mychaliska, George B.*,¶

doi: 10.1097/MAT.0000000000000939

An artificial placenta (AP) utilizing extracorporeal life support (ECLS) could protect premature lungs from injury and promote continued development. Preterm lambs at estimated gestational age (EGA) 114–128 days (term = 145) were delivered by Caesarian section and managed in one of three groups: AP, mechanical ventilation (MV), or tissue control (TC). Artificial placenta lambs (114 days EGA, n = 3; 121 days, n = 5) underwent venovenous (VV)-ECLS with jugular drainage and umbilical vein reinfusion for 7 days, with a fluid-filled, occluded airway. Mechanical ventilation lambs (121 days, n = 5; 128 days, n = 5) underwent conventional MV until failure or maximum 48 hours. Tissue control lambs (114 days, n = 3; 121 days, n = 5; 128 days, n = 5) were sacrificed at delivery. At the conclusion of each experiment, lungs were procured and sectioned. Hematoxylin and eosin (H&E) slides were scored 0–4 in seven injury categories, which were summed for a total injury score. Slides were also immunostained for platelet-derived growth factor receptor (PDGFR)-α and α-actin; lung development was quantified by the area fraction of double-positive tips of secondary alveolar septa. Support duration of AP lambs was 163 ± 9 (mean ± SD) hours, 4 ± 3 for early MV lambs, and 40 ± 6 for late MV lambs. Total injury scores at 121 days were 1.7 ± 2.1 for AP vs. 5.5 ± 1.6 for MV (p = 0.02). Using immunofluorescence, double-positive tip area fraction at 121 days was 0.017 ± 0.011 in AP lungs compared with 0.003 ± 0.003 in MV lungs (p < 0.001) and 0.009 ± 0.005 in TC lungs. At 128 days, double-positive tip area fraction was 0.012 ± 0.007 in AP lungs compared with 0.004 ± 0.004 in MV lungs (p < 0.001) and 0.016 ± 0.009 in TC lungs. The AP is protective against lung injury and promotes lung development compared with mechanical ventilation in premature lambs.

From the *Extracorporeal Life Support Laboratory, Department of Surgery, Michigan Medicine, Ann Arbor, Michigan

Departments of Pediatrics and Communicable Diseases, Michigan Medicine, Ann Arbor, Michigan

Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, Michigan

§Department of Pathology, Michigan Medicine, Ann Arbor, Michigan

Department of Pediatric Surgery, Fetal Diagnosis and Treatment Center, C.S. Mott Children’s Hospital, Michigan Medicine, Ann Arbor, Michigan.

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Submitted for consideration March 2018; accepted for publication in revised form October 2018.

Disclosure: The authors have no conflicts of interest to report.

This study was supported by National Institutes of Health Grant # 1R01HD073475-01A1.

The authors Werner, Church, and Perkins contributed equally to the manuscript.

Correspondence: Megan A. Coughlin, Extracorporeal Life Support Laboratory, Department of Surgery, Michigan Medicine, Ann Arbor, MI. Email:

Copyright © 2019 by the American Society for Artificial Internal Organs