Neuroprotective effects of amiodarone in a mouse model of ischemic stroke

BMC Anesthesiology

Research Article

Takashi Matsukawa¹  Masakazu Kotoda¹  Sohei Hishiyama¹  Kazuha Mitsui¹  Tadahiko Ishiyama² 

[1] Department of Anesthesiology, Faculty of Medicine, University of Yamanashi, 1110 Shimokato, 409-3898, Chuo, Yamanashi, Japan;Surgical Center, University of Yamanashi Hospital, University of Yamanashi, 1110 Shimokato, 409-3898, Chuo, Yamanashi, Japan;

关键词: Amiodarone;    Pre-treatment;    Stroke;    Neuroprotection;   

DOI  :  10.1186/s12871-017-0459-3

 received in 2017-06-19, accepted in 2017-11-27,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundIon channels play a crucial role in the development of ischemic brain injury. Recent studies have reported that the blockade of various types of ion channels improves outcomes in experimental stroke models. Amiodarone, one of the most effective drugs for life-threatening arrhythmia, works as a multiple channel blocker and its characteristics cover all four Vaughan-Williams classes. Although it is known that amiodarone indirectly contributes to preventing ischemic stroke by maintaining sinus rhythm in patients with atrial fibrillation, the direct neuroprotective effect of amiodarone has not been clarified. The purpose of this study was to investigate the direct effect of amiodarone on ischemic stroke in mice.MethodsFocal cerebral ischemia was induced via distal permanent middle cerebral artery occlusion (MCAO) in adult male mice. The amiodarone pre-treatment group received 50 mg/kg of amiodarone 1 h before MCAO; the amiodarone post-treatment groups received 50 mg/kg of amiodarone immediately after MCAO; the control group received vehicle only. In addition, the sodium channel opener veratrine and selective beta-adrenergic agonist isoprotelenol were used to elucidate the targeted pathway. Heart rate and blood pressure were monitored perioperatively. Infarct volume analysis was conducted 48 h after MCAO. The body asymmetry test and the corner test were used for neurological evaluation.ResultsAmiodarone pre-treatment and post-treatment reduced the heart rate but did not affect the blood pressure. No mice showed arrhythmia. Compared with the control group, the amiodarone pre-treatment group had smaller infarct volumes (8.9 ± 2.1% hemisphere [mean ± SD] vs. 11.2 ± 1.4%; P < 0.05) and improved functional outcomes: lower asymmetric body swing rates (52 ± 17% vs. 65 ± 18%; P < 0.05) and fewer left turns (7.1 ± 1.2 vs. 8.3 ± 1.2; P < 0.05). In contrast, amiodarone post-treatment did not improve the outcomes after MCAO. The neuroprotective effect of amiodarone pre-treatment was abolished by co-administration of veratrine but not by isoproterenol.ConclusionsAmiodarone pre-treatment attenuated ischemic brain injury and improved functional outcomes without affecting heart rhythm and blood pressure. The present results showed that amiodarone pre-treatment has neuroprotective effects, at least in part, via blocking the sodium channels.

【 授权许可】

CC BY   
© The Author(s). 2017