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

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 (similar to 0.75%) to deep (similar to 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 (similar to 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.