Longitudinal Impact on Rat Cardiac Tissue Transcriptomic Profiles Due to Acute Intratracheal Inhalation Exposures to Isoflurane

Details

• Personal Author:
  Chen L-C ; Cohen MD ; Costa M ; Horton L ; Kluz T ; Lee H-W ; Lu Y ; Park S-H ; Prophete C ; Shao Y ; Sisco M ; Sun H ; Zelikoff J
• Description:
  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. [Description provided by NIOSH]
• Subjects:
  Anesthesia Cardiovascular System Immune System Laboratories Occupational Health Respiratory System Safety
• Keywords:
  Anesthetics Cardiac Function Cell Signaling Exposure Assessment Gene Expression Gene Regulation Immune Reaction Inhalation Laboratory Animals
• ISSN:
  1932-6203
• Document Type:
  Text
• Funding:
  Grant ; Cooperative Agreement
• Genre:
  Journal Article
• Place as Subject:
  New York ; Ohio ; OSHA Region 2 ; OSHA Region 5
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  16
• Issue:
  10
• NIOSHTIC Number:
  nn:20064065
• Citation:
  PLoS One 2021 Oct; 16(10):e0257241
• Contact Point Address:
  Sung-Hyun Park, Department of Environmental Medicine, New York University Grossman School of Medicine, New York, NY, United States of America
• Email:
  SungHyun.Park@nyulangone.org
• CAS Registry Number:
  Isoflurane (CAS RN 266Trifluoromethane (CAS RN 75-46-7))
• Federal Fiscal Year:
  2022
• Performing Organization:
  New York University School of Medicine
• Peer Reviewed:
  True
• Start Date:
  20090701
• Source Full Name:
  PLoS One
• End Date:
  20140630
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:b11b6c3d129ba70866914f1f7a1c36d2cecc62bc2274d1fb4ff60f09f13690bc1c1068e5a20b713a222a35dfc3e1cc2c377349e572ff1a5558841867516000ed
• Download URL:
  https://stacks.cdc.gov/view/cdc/222591/cdc_222591_DS1.pdf
• File Type:
  [PDF - 4.97 MB ]