• Kotaro Kida, Shizuka Minamishima, Huifang Wang, JiaQian Ren, Kazim Yigitkanli, Ala Nozari, Joseph B Mandeville, Philip K Liu, Christina H Liu, and Fumito Ichinose.
• Department of Anaesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02129, USA.
• Resuscitation. 2012 Oct 1;83(10):1292-7.

Aim Of The StudySudden cardiac arrest (CA) is one of the leading causes of death worldwide. Previously we demonstrated that administration of sodium sulfide (Na(2)S), a hydrogen sulfide (H(2)S) 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 Na(2)S and its impact on the long-term survival after CA/CPR in mice.MethodsAdult male mice were subjected to potassium-induced CA for 7.5 min at 37°C whereupon CPR was performed with chest compression and mechanical ventilation. Mice received Na(2)S (0.55 mgkg(-1) i.v.) or vehicle 1 min before CPR.ResultsMice 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 Na(2)S 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.ConclusionThese results suggest that administration of Na(2)S 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.Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

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