title: Sodium sulfide prevents water diffusion abnormality in the brain and improves long term outcome after cardiac arrest in mice.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Anaesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02129, USA.
authors.forename: Kotaro
authors.initials: K
authors.lastname: Kida
authors.forename: Shizuka
authors.initials: S
authors.lastname: Minamishima
authors.forename: Huifang
authors.initials: H
authors.lastname: Wang
authors.forename: JiaQian
authors.initials: J
authors.lastname: Ren
authors.forename: Kazim
authors.initials: K
authors.lastname: Yigitkanli
authors.forename: Ala
authors.initials: A
authors.lastname: Nozari
authors.forename: Joseph B
authors.initials: JB
authors.lastname: Mandeville
authors.forename: Philip K
authors.initials: PK
authors.lastname: Liu
authors.forename: Christina H
authors.initials: CH
authors.lastname: Liu
authors.forename: Fumito
authors.initials: F
authors.lastname: Ichinose
mesh_terms: D000818:Animals; D001921:Brain / Q000503:physiopathology*; D016887:Cardiopulmonary Resuscitation; D004058:Diffusion; D006323:Heart Arrest / Q000401:mortality / Q000503:physiopathology* / Q000628:therapy*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D013440:Sulfides / Q000627:therapeutic use*; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D013440:Sulfides; C033479:sodium sulfide