Hydrogen sulfide improves survival after cardiac arrest and cardiopulmonary resuscitation via a nitric oxide synthase 3-dependent mechanism in mice

Shizuka Minamishima, Masahiko Bougaki, Patrick Y. Sips, Jia De Yu, Yoji Andrew Minamishima, John W. Elrod, David J. Lefer, Kenneth D. Bloch, Fumito Ichinose

Research output: Contribution to journalArticle

149 Citations (Scopus)

Abstract

Sudden cardiac arrest (CA) is one of the leading causes of death worldwide. We sought to evaluate the impact of hydrogen sulfide (H 2S) on the outcome after CA and cardiopulmonary resuscitation (CPR) in mouse. Methods and Results-Mice were subjected to 8 minutes of normothermic CA and resuscitated with chest compression and mechanical ventilation. Seven minutes after the onset of CA (1 minute before CPR), mice received sodium sulfide (Na 2S) (0.55 mg/kg IV) or vehicle 1 minute before CPR. There was no difference in the rate of return of spontaneous circulation, CPR time to return of spontaneous circulation, and left ventricular function at return of spontaneous circulation between groups. Administration Of Na 2S 1 minute before CPR markedly improved survival rate at 24 hours after CPR (15/15) compared with vehicle (10/26; P=0.000l versus Na 2S). Administration Of Na 2S prevented CA/CPR-induced oxidative stress and ameliorated left ventricular and neurological dysfunction 24 hours after CPR. Delayed administration Of Na 2S at 10 minutes after CPR did not improve outcomes after CA/CPR. Cardioprotective effects of Na2S were confirmed in isolated-perfused mouse hearts subjected to global ischemia and reperfusion. Cardiomyocyte-specific overexpression of cystathionine γ-lyase (an enzyme that produces H 2S) markedly improved outcomes of CA/CPR. Na 2S increased phosphorylation of nitric oxide synthase 3 in left ventricle and brain cortex, increased serum nitrite/nitrate levels, and attenuated CA-induced mitochondrial injury and cell death. Nitric oxide synthase 3 deficiency abrogated the protective effects of Na 2S on the outcome of CA/CPR. Conclusions-These results suggest that administration of Na 2S at the time of CPR improves outcome after CA possibly via a nitric oxide synthase 3-dependent signaling pathway.

Original languageEnglish
Pages (from-to)888-896
Number of pages9
JournalCirculation
Volume120
Issue number10
DOIs
Publication statusPublished - 2009 Nov 17
Externally publishedYes

Keywords

  • Apoptosis
  • Cardiopulmonary resuscitation
  • Heart arrest
  • Myocardial contraction
  • Nitric oxide synthase
  • Physiology

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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    Minamishima, S., Bougaki, M., Sips, P. Y., De Yu, J., Minamishima, Y. A., Elrod, J. W., Lefer, D. J., Bloch, K. D., & Ichinose, F. (2009). Hydrogen sulfide improves survival after cardiac arrest and cardiopulmonary resuscitation via a nitric oxide synthase 3-dependent mechanism in mice. Circulation, 120(10), 888-896. https://doi.org/10.1161/CIRCULATIONAHA.108.833491