Sodium sulfide prevents water diffusion abnormality in the brain and improves long term outcome after cardiac arrest in mice

RESUSCITATION

卷:83

Article

Kida, Kotaro^1,2  Minamishima, Shizuka^1,2  Wang, Huifang^2,3  Ren, JiaQian^2,3  Yigitkanli, Kazim^2,3,4  Nozari, Ala^1,2  Mandeville, Joseph B.^2,3  Liu, Philip K.^2,3  Liu, Christina H.^2,3  Ichinose, Fumito^1,2 

[1] Massachusetts Gen Hosp, Dept Anaesthesia Crit Care & Pain Med, Boston, MA 02114 USA

[2] Harvard Univ, Sch Med, Boston, MA USA

[3] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA

[4] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA

关键词: Cardiac arrest;    Resuscitation;    Hydrogen sulfide;    Magnetic resonance imaging;    Matrix metalloproteinase 9;    Blood brain barrier;   

DOI  :  10.1016/j.resuscitation.2012.02.020

来源: Elsevier

【 摘 要 】

Aim of the study: Sudden cardiac arrest (CA) is one of the leading causes of death worldwide. Previously we demonstrated that administration of sodium sulfide (Na2S), a hydrogen sulfide (H2S) donor, markedly improved the neurological outcome and survival rate at 24 h after CA and cardiopulmonary resuscitation (CPR) in mice. In this study, we sought to elucidate the mechanism responsible for the neuroprotective effects of Na2S and its impact on the long-term survival after CA/CPR in mice. Methods: Adult male mice were subjected to potassium-induced CA for 7.5 min at 37 degrees C whereupon CPR was performed with chest compression and mechanical ventilation. Mice received Na2S (0.55 mg kg(-1) i.v.) or vehicle 1 min before CPR. Results: Mice that were subjected to CA/CPR and received vehicle exhibited a poor 10-day survival rate (4/12) and depressed neurological function. Cardiac arrest and CPR induced abnormal water diffusion in the vulnerable regions of the brain, as demonstrated by hyperintense diffusion-weighted imaging (DWI) 24 h after CA/CPR. Extent of hyperintense DWI was associated with matrix metalloproteinase 9 (MMP-9) activation, worse neurological outcomes, and poor survival rate at 10 days after CA/CPR. Administration of Na2S prevented the development of abnormal water diffusion and MMP-9 activation and markedly improved neurological function and long-term survival (9/12, P < 0.05 vs. Vehicle) after CA/CPR. Conclusion: These results suggest that administration of Na2S 1 min before CPR improves neurological function and survival rate at 10 days after CA/CPR by preventing water diffusion abnormality in the brain potentially via inhibiting MMP-9 activation early after resuscitation. (C) 2012 Elsevier Ireland Ltd. All rights reserved.

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