Joseph T Church1, Megan A Coughlin2, Elena M Perkins2, Hayley R Hoffman2, John D Barks3, Raja Rabah4, J Kelley Bentley5, Marc B Hershenson5, Robert H Bartlett2, George B Mychaliska6. 1. Extracorporeal Life Support Laboratory, Department of Surgery, Michigan Medicine, B560 MSRB II/SPC 5686, 1150 W. Medical Center Dr., Ann Arbor, MI, USA. Electronic address: jchurc@med.umich.edu. 2. Extracorporeal Life Support Laboratory, Department of Surgery, Michigan Medicine, B560 MSRB II/SPC 5686, 1150 W. Medical Center Dr., Ann Arbor, MI, USA. 3. Departments of Pediatrics and Communicable Diseases, Michigan Medicine, 1540 E. Medical Center Dr., Ann Arbor, MI, USA. 4. Department of Pathology, Michigan Medicine, 1500 E. Medical Center Dr., Ann Arbor, MI, USA. 5. Departments of Pediatrics and Communicable Diseases, Michigan Medicine, 1540 E. Medical Center Dr., Ann Arbor, MI, USA; Department of Molecular and Integrative Physiology, University of Michigan Medical School, 1301 Catherine St., Ann Arbor, MI. 6. Extracorporeal Life Support Laboratory, Department of Surgery, Michigan Medicine, B560 MSRB II/SPC 5686, 1150 W. Medical Center Dr., Ann Arbor, MI, USA; Fetal Diagnosis and Treatment Center, C.S. Mott Children's Hospital, Michigan Medicine, 1540 E. Medical Center Dr., Ann Arbor, MI.
Abstract
PURPOSE: An artificial placenta (AP) utilizing extracorporeal life support (ECLS) could avoid the harm of mechanical ventilation (MV) while allowing the lungs to develop. METHODS: AP lambs (n = 5) were delivered at 118 days gestational age (GA; term = 145 days) and placed on venovenous ECLS (VV-ECLS) with jugular drainage and umbilical vein reinfusion. Lungs remained fluid-filled. After 10 days, lambs were ventilated. MV control lambs were delivered at 118 ("early MV"; n = 5) or 128 days ("late MV"; n = 5), and ventilated. Compliance and oxygenation index (OI) were calculated. After sacrifice, lungs were procured and H&E-stained slides scored for lung injury. Slides were also immunostained for PDGFR-α and α-actin; alveolar development was quantified by the area fraction of alveolar septal tips staining double-positive for both markers. RESULTS: Compliance of AP lambs was 2.79 ± 0.81 Cdyn compared to 0.83 ± 0.19 and 3.04 ± 0.99 for early and late MV, respectively. OI in AP lambs was lower than early MV lambs (6.20 ± 2.10 vs. 36.8 ± 16.8) and lung injury lower as well (1.8 ± 1.6 vs. 6.0 ± 1.2). Double-positive area fractions were higher in AP lambs (0.012 ± 0.003) than early (0.003 ± 0.0005) and late (0.004 ± 0.002) MV controls. CONCLUSIONS: Lung development continues and lungs are protected from injury during AP support relative to mechanical ventilation. LEVEL OF EVIDENCE: n/a (basic/translational science).
PURPOSE: An artificial placenta (AP) utilizing extracorporeal life support (ECLS) could avoid the harm of mechanical ventilation (MV) while allowing the lungs to develop. METHODS: AP lambs (n = 5) were delivered at 118 days gestational age (GA; term = 145 days) and placed on venovenous ECLS (VV-ECLS) with jugular drainage and umbilical vein reinfusion. Lungs remained fluid-filled. After 10 days, lambs were ventilated. MV control lambs were delivered at 118 ("early MV"; n = 5) or 128 days ("late MV"; n = 5), and ventilated. Compliance and oxygenation index (OI) were calculated. After sacrifice, lungs were procured and H&E-stained slides scored for lung injury. Slides were also immunostained for PDGFR-α and α-actin; alveolar development was quantified by the area fraction of alveolar septal tips staining double-positive for both markers. RESULTS: Compliance of AP lambs was 2.79 ± 0.81 Cdyn compared to 0.83 ± 0.19 and 3.04 ± 0.99 for early and late MV, respectively. OI in AP lambs was lower than early MV lambs (6.20 ± 2.10 vs. 36.8 ± 16.8) and lung injury lower as well (1.8 ± 1.6 vs. 6.0 ± 1.2). Double-positive area fractions were higher in AP lambs (0.012 ± 0.003) than early (0.003 ± 0.0005) and late (0.004 ± 0.002) MV controls. CONCLUSIONS: Lung development continues and lungs are protected from injury during AP support relative to mechanical ventilation. LEVEL OF EVIDENCE: n/a (basic/translational science).
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