J Anesth Perioper Med. 2017;4(5):205-212. https://doi.org/10.24015/ebcmed.japm.2017.0011

Hyperpolarization-Activated Cyclic Nucleotide-Gated Channel Blocker ZD7288 Prevents Sevoflurane-Induced Hyperactivity in A Novel Mice Behavioral Model

Peng Liang1,2*, Xu-Bin Huang4*, Feng-Shan Li1, Han Huang1,3, Jing-Xuan Qiu2, Da-Qing Liao1, Jin Liu1,2, and Cheng Zhou1,5

From 1Lab of Anesthesia & Critical Care Medicine, Translational Neuroscience Center, West China Hospital of Sichuan University, Chengdu, China; 2Department of Anesthesiology, West China Hospital of Sichuan University, Chengdu, China; 3Department of Anesthesiology, West China Second Hospital of Sichuan University, Sichuan, China; 4Department of Forensic Medicine, Jinjiang District Branch of Chengdu City Public Security Bureau, Sichuan, China; 5Department of Anesthesiology, Weill Medical College of Cornell University, New York, USA.

*The authors contributed equally to this study.

Correspondence to Dr. Cheng Zhou at zhouc@163.com or zhouc1985@gmail.com.

EBCMED ID: ebcmed.japm.2017.0011 DOI: 10.24015/ebcmed.japm.2017.0011


Besides effect of general anesthesia, sevoflurane also induces hyperactivity during induction and recovery, especially in young children. Lack of satisfied animal model impedes the investigation of causes of the hyperactivity as well as its prevention. Hyperpolarization-activated cyclic nucleotide-gated (HCN) channel blocker might produce sedative effect. This study developed a novel mice model of hyperactive behaviors and further explored effects of HCN channel blocker on sevofluraneinduced hyperactivity.

C57BL/6 mice were used in the present study. Maximal speed, mean speed, total movement distance and resting percentage of mice were quantitatively measured by behavioral tracking software. Age-dependence of this model was also analyzed. HCN channel blocker ZD7288 at doses of 6.25 and 12.5 μg/kg were intraperitoneal injected to prevent sevoflurane-induced hyperactivity.

In the behavioral model, sevoflurane could induce significant hyperactivity in mice under 1% sevoflurane inhalation and in recovery period, characterized as increased movement speed and total distance. The sevoflurane- induced hyperactivity was more significant in young mice than adult (P<0.01). Pre- administration of ZD7288 could significantly prevent sevoflurane-induced hyperactivity.

The mice behavioral model developed in this study could characterize sevoflurane-induced hyperactivity in induction and recovery period as well as age-dependence. In addition, by this animal model, HCN channel blocker ZD7288 could prevent sevoflurane-induced hyperactivity. Thus, HCN channel might be the underlying therapeutic target for sevoflurane-induced agitation in general anesthesia.

Article Type
Original Article

Declaration of Interests
All authors have no other potential conflicts of interest for this study to declare.

This study was supported by a grant from the National Natural Science Foundation of China: (NSFC, No.81371511 and No.31171013).

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