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

• Published in: Resuscitation 2012-10, Vol.83 (10), p.1292-1297
• Main Authors: Kida, Kotaro, Minamishima, Shizuka, Wang, Huifang, Ren, JiaQian, Yigitkanli, Kazim, Nozari, Ala, Mandeville, Joseph B, Liu, Philip K, Liu, Christina H, Ichinose, Fumito
• Format: Article
• Language: English
• Subjects: Animals; Blood brain barrier; Brain - physiopathology; Cardiac arrest; Cardiopulmonary Resuscitation; Diffusion; Emergency; Heart Arrest - mortality; Heart Arrest - physiopathology; Heart Arrest - therapy; Hydrogen sulfide; Magnetic resonance imaging; Male; Matrix metalloproteinase 9; Mice; Mice, Inbred C57BL; Resuscitation; Sulfides - therapeutic use; Survival Rate; Treatment Outcome
• ISSN: 0300-9572; 1873-1570
• DOI: 10.1016/j.resuscitation.2012.02.020

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 (Na2 S), a hydrogen sulfide (H2 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 Na2 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 Na2 S (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 Na2 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 Na2 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.