Premature Lambs Exhibit Normal Mitochondrial Respiration after Long-Term Extrauterine Support.


Journal

Fetal diagnosis and therapy
ISSN: 1421-9964
Titre abrégé: Fetal Diagn Ther
Pays: Switzerland
ID NLM: 9107463

Informations de publication

Date de publication:
2019
Historique:
received: 28 09 2018
accepted: 13 12 2018
pubmed: 13 3 2019
medline: 9 4 2020
entrez: 13 3 2019
Statut: ppublish

Résumé

In an effort to mitigate the major morbidities and mortality associated with extreme prematurity, we have developed an EXTrauterine Environment for Neonatal Development (EXTEND) designed to provide physiologic support of extremely premature infants. We have previously shown that long-term, physiologic support of premature fetal lambs is possible with EXTEND, but in this study, we sought to demonstrate bioenergetic equipoise at the tissue level. Four premature fetal lambs were delivered by hysterotomy at gestational ages (GA) of 105-107 days (term ∼145 days), cannulated via the umbilical vessels, and transitioned to support on EXTEND for 3-4 weeks. Five control fetuses were age-matched to the GA of experimental fetuses at the time of study end (128-134 days GA) and immediately sacrificed after hysterotomy. Mitochondria were isolated from the heart, liver, kidney, and skeletal muscle of fetuses at the time of sacrifice, and oxygen consumption rates (OCRs) were measured. There were no differences in basal mitochondrial OCR between EXTEND and control fetuses for heart, kidney, or skeletal muscle. For liver, the basal OCR was higher in EXTEND fetuses compared to controls. There were no differences in physiologic maximal OCR or reserve capacity for any tissue analyzed. Fetal lambs supported by EXTEND demonstrate physiologic mitochondrial function as evidenced by adequate basal and physiologic maximal cellular respiration as well as preserved reserve capacity.

Sections du résumé

BACKGROUND BACKGROUND
In an effort to mitigate the major morbidities and mortality associated with extreme prematurity, we have developed an EXTrauterine Environment for Neonatal Development (EXTEND) designed to provide physiologic support of extremely premature infants.
OBJECTIVES OBJECTIVE
We have previously shown that long-term, physiologic support of premature fetal lambs is possible with EXTEND, but in this study, we sought to demonstrate bioenergetic equipoise at the tissue level.
METHODS METHODS
Four premature fetal lambs were delivered by hysterotomy at gestational ages (GA) of 105-107 days (term ∼145 days), cannulated via the umbilical vessels, and transitioned to support on EXTEND for 3-4 weeks. Five control fetuses were age-matched to the GA of experimental fetuses at the time of study end (128-134 days GA) and immediately sacrificed after hysterotomy. Mitochondria were isolated from the heart, liver, kidney, and skeletal muscle of fetuses at the time of sacrifice, and oxygen consumption rates (OCRs) were measured.
RESULTS RESULTS
There were no differences in basal mitochondrial OCR between EXTEND and control fetuses for heart, kidney, or skeletal muscle. For liver, the basal OCR was higher in EXTEND fetuses compared to controls. There were no differences in physiologic maximal OCR or reserve capacity for any tissue analyzed.
CONCLUSIONS CONCLUSIONS
Fetal lambs supported by EXTEND demonstrate physiologic mitochondrial function as evidenced by adequate basal and physiologic maximal cellular respiration as well as preserved reserve capacity.

Identifiants

pubmed: 30861524
pii: 000496232
doi: 10.1159/000496232
doi:

Substances chimiques

Biomarkers 0
8-Hydroxy-2'-Deoxyguanosine 88847-89-6
Bilirubin RFM9X3LJ49

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

306-312

Informations de copyright

© 2019 S. Karger AG, Basel.

Auteurs

Avery C Rossidis (AC)

Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA, avery.rossidis@uphs.upenn.edu.

Alessia Angelin (A)

Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.

Kendall M Lawrence (KM)

Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.

Heron D Baumgarten (HD)

Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.

Aimee G Kim (AG)

Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.

Ali Y Mejaddam (AY)

Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.

Barbara E Coons (BE)

Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.

Heather A Hartman (HA)

Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.

Grace Hwang (G)

Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.

Stylianos Monos (S)

Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.

William H Peranteau (WH)

Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.

Marcus G Davey (MG)

Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.

Deborah Murdock (D)

Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.

Douglas C Wallace (DC)

Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.

Alan W Flake (AW)

Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
Department of Surgery, Children's Hospital of Philadelphia, Abramson Research Center, Philadelphia, Pennsylvania, USA.

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Classifications MeSH