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

Abstract

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 (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. METHODS Adult 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. 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 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. CONCLUSION These 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.

DOI: 10.1016/j.resuscitation.2012.02.020
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@article{Kida2012SodiumSP, title={Sodium sulfide prevents water diffusion abnormality in the brain and improves long term outcome after cardiac arrest in mice.}, author={Kotaro Kida and Shizuka Minamishima and Huifang Wang and Jiaqian Ren and Kazim Yiğitkanli and Ala Nozari and Joseph B. Mandeville and Philip K. Liu and Christina Liu and Fumito Ichinose}, journal={Resuscitation}, year={2012}, volume={83 10}, pages={1292-7} }