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Author Notes:

Correspondence to: Xiaodong Zhang, Ph.D, Yerkes Imaging Center, Yerkes National Primate Research Center, Emory University, Address: 954 Gatewood Rd NE, Atlanta, GA 30329, Fax: (404) 712-9807, Phone: (404) 712-9874, xzhang8@emory.edu.

The authors are grateful to Sudeep Patel, Ruth Connelly, and Doty Kempt (DVM) for assistance in data acquisition and animal handling.

The authors have no conflict of interest to claim.


Research Funding:

The project was funded by the National Center for Research Resources (P51RR000165) and is currently supported by the Office of Research Infrastructure Programs (OD P51OD011132).


  • Anesthesia
  • CBF
  • Default mode network (DMN)
  • Dosage effect
  • Functional MRI
  • Non-human primate
  • Pseudo continuous arterial-spin-labeling (pCASL)
  • Anesthetics, Inhalation
  • Animals
  • Brain
  • Cerebrovascular Circulation
  • Female
  • Isoflurane
  • Macaca mulatta

Evaluation of prolonged administration of isoflurane on cerebral blood flow and default mode network in macaque monkeys anesthetized with different maintenance doses


Journal Title:

Neuroscience Letters


Volume 662


, Pages 402-408

Type of Work:

Article | Post-print: After Peer Review


Object Isoflurane is a commonly used volatile anesthetic agent in clinical anesthesia and biomedical research. Prior study suggested the cerebral blood flow (CBF) and default mode network (DMN) could be changed after prolonged administration of isoflurane. The normal maintenance doses of isoflurane may vary from light (∼0.75%) to deep (∼1.5 or 2%) anesthesia. However, it is not clear how the duration effects are affected by the altered doses. The present study is aimed to examine if the duration effects are affected when isoflurane concentration is altered within normal maintenance doses. Materials and methods Adult rhesus monkeys (n = 5, 8–12 years old, 8–10 kg) were anesthetized and maintained at isoflurane levels 0.89 ± 0.03%, 1.05 ± 0.12%, or 1.19 ± 0.08%. CBF and DMN of monkeys were examined using arterial spin-labeling perfusion and resting state functional MRI techniques. Results the functional connectivity (FC) in the dominant DMN (posterior cingulate cortex (PCC) to anterior cingulated cortex (ACC) or media prefrontal cortex (MPFC)) decreased substantially and similarly during 4-h administration of isoflurane at any given maintenance dosage. CBF changes varied with isoflurane dosage. At the low dose (∼0.89%), CBF decreased in most brain regions. In contrast, no obvious changes was seen in those regions (except for the subcortex) when higher doses of isoflurane were applied. Conclusion FC in DMN was reduced substantially during prolonged administration of isoflurane. The FC reduction was not varying significantly with maintenance doses of isoflurane but the duration effect on CBF was dose-dependent. Such duration effects of isoflurane administration on DMN and CBF should be considered in the interpretation of the outcome in related neuroimaging studies of anesthetized subjects.

Copyright information:

© 2017 Elsevier B.V.

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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