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Isoflurane tolerance against focal cerebral ischemia is attenuated by adenosine A₁ receptor antagonists

[La tolérance à l’isoflurane contre l’ischémie cérébrale focale est diminuée par les antagonistes des récepteurs de l’adénosine A₁]

From the Department of Anesthesiology, Xijing Hospital, Fourth Military Medical University, Xi’an, Shaanxi, China

Address correspondence to: Dr. Lize Xiong, Department of Anesthesiology, Xijing Hospital, Xi’an, Shaanxi Province 710032, China. Phone: +86-29-84775337; Fax: +86-29-83244986; E-mail: lxiong{at}fmmu.edu.cn

Purpose: To investigate the role of the adenosine A₁ receptor in the rapid tolerance to cerebral ischemia induced by isoflurane preconditioning.

Methods: Seventy-five rats were randomly assigned into five groups (n = 15 each): Control, 8-cyclopentyl-1,3-dipropulxanthine (DPCPX), Isoflurane, DPCPX+Isoflurane and Vehicle+Isoflurane groups. All animals underwent right middle cerebral artery occlusion (MCAO) for two hours. Isoflurane preconditioning was conducted one hour before MCAO in Isoflurane, DPCPX+Isoflurane and Vehicle+Isoflurane groups by exposing the animals to 1.5% isoflurane in 98% oxygen for one hour. In the Control and DPCPX groups, animals were exposed to 98% oxygen one hour before MCAO for one hour. A selective adenosine A₁ receptor antagonist, DPCPX, was administered (0.1 mg·kg^–1) 15 min before isoflurane/oxygen exposure in the DPCPX and DPCPX+Isoflurane groups to evaluate the effect of adenosine A₁ receptor antagonist on isoflurane preconditioning. Dimethyl sulfoxide, the solvent of DPCPX, was administered (1 mL·kg^–1) 15 min before isoflurane exposure in the Vehicle+Isoflurane group. Neurological deficit scores and brain infarct volumes were evaluated 24 hr after reperfusion.

Results: Animals in the Isoflurane and Vehicle+Isoflurane groups developed lower neurological deficit scores and smaller brain infarct volumes than the Control group (P < 0.01). Animals in the DPCPX+Isoflurane group developed higher neurological deficit scores and larger brain infarct volumes than the Isoflurane and Vehicle+Isoflurane groups (P < 0.01).

Conclusion: The present study demonstrates that preconditioning with isoflurane reduces focal cerebral ischemic injury in rats, and the adenosine A₁ receptor antagonist (DPCPX) attenuates the neuroprotection induced by isoflurane preconditioning.

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