Inhaled nitric oxide improves outcomes after successful cardiopulmonary resuscitation in mice

Shizuka Minamishima, Kotaro Kida, Kentaro Tokuda, Huifang Wang, Patrick Y. Sips, Shizuko Kosugi, Joseph B. Mandeville, Emmanuel S. Buys, Peter Brouckaert, Philip K. Liu, Christina H. Liu, Kenneth D. Bloch, Fumito Ichinose

Research output: Contribution to journalArticlepeer-review

83 Citations (Scopus)


Background-: Sudden cardiac arrest (CA) is a leading cause of death worldwide. Breathing nitric oxide (NO) reduces ischemia/reperfusion injury in animal models and in patients. The objective of this study was to learn whether inhaled NO improves outcomes after CA and cardiopulmonary resuscitation (CPR). Methods and Results-: Adult male mice were subjected to potassium-induced CA for 7.5 minutes whereupon CPR was performed with chest compression and mechanical ventilation. One hour after CPR, mice were extubated and breathed air alone or air supplemented with 40 ppm NO for 23 hours. Mice that were subjected to CA/CPR and breathed air exhibited a poor 10-day survival rate (4 of 13), depressed neurological and left ventricular function, and increased caspase-3 activation and inflammatory cytokine induction in the brain. Magnetic resonance imaging revealed brain regions with marked water diffusion abnormality 24 hours after CA/CPR in mice that breathed air. Breathing air supplemented with NO for 23 hours starting 1 hour after CPR attenuated neurological and left ventricular dysfunction 4 days after CA/CPR and markedly improved 10-day survival rate (11 of 13; P=0.003 versus mice breathing air). The protective effects of inhaled NO on the outcome after CA/CPR were associated with reduced water diffusion abnormality, caspase-3 activation, and cytokine induction in the brain and increased serum nitrate/nitrite levels. Deficiency of the α1 subunit of soluble guanylate cyclase, a primary target of NO, abrogated the ability of inhaled NO to improve outcomes after CA/CPR. Conclusions-: These results suggest that NO inhalation after CA and successful CPR improves outcome via soluble guanylate cyclase-dependent mechanisms.

Original languageEnglish
Pages (from-to)1645-1653
Number of pages9
Issue number15
Publication statusPublished - 2011 Oct 11
Externally publishedYes


  • cardiopulmonary resuscitation
  • heart arrest
  • magnetic resonance imaging
  • nitric oxide synthase
  • physiology

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)


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