Longitudinal impact on rat cardiac tissue transcriptomic profiles due to acute intratracheal inhalation exposures to isoflurane.


Journal

PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081

Informations de publication

Date de publication:
2021
Historique:
received: 26 03 2021
accepted: 26 08 2021
entrez: 14 10 2021
pubmed: 15 10 2021
medline: 25 11 2021
Statut: epublish

Résumé

Isoflurane (ISO) is a widely used inhalation anesthetic in experiments with rodents and humans during surgery. Though ISO has not been reported to impart long-lasting side effects, it is unknown if ISO can influence gene regulation in certain tissues, including the heart. Such changes could have important implications for use of this anesthetic in patients susceptible to heart failure/other cardiac abnormalities. To test if ISO could alter gene regulation/expression in heart tissues, and if such changes were reversible, prolonged, or late onset with time, SHR (spontaneously hypertensive) rats were exposed by intratracheal inhalation to a 97.5% air/2.5% ISO mixture on two consecutive days (2 hr/d). Control rats breathed filtered air only. On Days 1, 30, 240, and 360 post-exposure, rat hearts were collected and total RNA was extracted from the left ventricle for global gene expression analysis. The data revealed differentially-expressed genes (DEG) in response to ISO (compared to naïve control) at all post-exposure timepoints. The data showed acute ISO exposures led to DEG associated with wounding, local immune function, inflammation, and circadian rhythm regulation at Days 1 and 30; these effects dissipated by Day 240. There were other significantly-increased DEG induced by ISO at Day 360; these included changes in expression of genes associated with cell signaling, differentiation, and migration, extracellular matrix organization, cell-substrate adhesion, heart development, and blood pressure regulation. Examination of consistent DEG at Days 240 and 360 indicated late onset DEG reflecting potential long-lasting effects from ISO; these included DEG associated with oxidative phosphorylation, ribosome, angiogenesis, mitochondrial translation elongation, and focal adhesion. Together, the data show acute repeated ISO exposures could impart variable effects on gene expression/regulation in the heart. While some alterations self-resolved, others appeared to be long-lasting or late onset. Whether such changes occur in all rat models or in humans remains to be investigated.

Identifiants

pubmed: 34648499
doi: 10.1371/journal.pone.0257241
pii: PONE-D-21-09743
pmc: PMC8516213
doi:

Substances chimiques

Anesthetics, Inhalation 0
Isoflurane CYS9AKD70P

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, U.S. Gov't, Non-P.H.S.

Langues

eng

Sous-ensembles de citation

IM

Pagination

e0257241

Subventions

Organisme : NIOSH CDC HHS
ID : R01 OH010921
Pays : United States
Organisme : NIOSH CDC HHS
ID : U01 OH012056
Pays : United States
Organisme : NIEHS NIH HHS
ID : P30 ES000260
Pays : United States
Organisme : NIOSH CDC HHS
ID : R01 OH008280
Pays : United States

Déclaration de conflit d'intérêts

The authors have declared that no competing interests exist.

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Auteurs

Sung-Hyun Park (SH)

Department of Environmental Medicine, New York University Grossman School of Medicine, New York, NY, United States of America.

Yuting Lu (Y)

Departments of Population Health & Environmental Medicine, New York University Grossman School of Medicine, New York, NY, United States of America.

Yongzhao Shao (Y)

Departments of Population Health & Environmental Medicine, New York University Grossman School of Medicine, New York, NY, United States of America.

Colette Prophete (C)

Department of Environmental Medicine, New York University Grossman School of Medicine, New York, NY, United States of America.

Lori Horton (L)

Department of Environmental Medicine, New York University Grossman School of Medicine, New York, NY, United States of America.

Maureen Sisco (M)

Department of Environmental Medicine, New York University Grossman School of Medicine, New York, NY, United States of America.

Hyun-Wook Lee (HW)

Department of Environmental Medicine, New York University Grossman School of Medicine, New York, NY, United States of America.

Thomas Kluz (T)

Department of Environmental Medicine, New York University Grossman School of Medicine, New York, NY, United States of America.

Hong Sun (H)

Department of Environmental Medicine, New York University Grossman School of Medicine, New York, NY, United States of America.

Max Costa (M)

Department of Environmental Medicine, New York University Grossman School of Medicine, New York, NY, United States of America.

Judith Zelikoff (J)

Department of Environmental Medicine, New York University Grossman School of Medicine, New York, NY, United States of America.

Lung-Chi Chen (LC)

Department of Environmental Medicine, New York University Grossman School of Medicine, New York, NY, United States of America.

Mitchell D Cohen (MD)

Department of Environmental Medicine, New York University Grossman School of Medicine, New York, NY, United States of America.

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