title: Inhaled nitric oxide improves outcomes after successful cardiopulmonary resuscitation in mice.
abstract: 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).
  
  
  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.
authors.affiliation: Anesthesia Center for Critical Care Research of the Department of Anesthesia, Critical Care, and Pain Medicine, Ghent University, Ghent, Belgium.
authors.forename: Shizuka
authors.initials: S
authors.lastname: Minamishima
authors.forename: Kotaro
authors.initials: K
authors.lastname: Kida
authors.forename: Kentaro
authors.initials: K
authors.lastname: Tokuda
authors.forename: Huifang
authors.initials: H
authors.lastname: Wang
authors.forename: Patrick Y
authors.initials: PY
authors.lastname: Sips
authors.forename: Shizuko
authors.initials: S
authors.lastname: Kosugi
authors.forename: Joseph B
authors.initials: JB
authors.lastname: Mandeville
authors.forename: Emmanuel S
authors.initials: ES
authors.lastname: Buys
authors.forename: Peter
authors.initials: P
authors.lastname: Brouckaert
authors.forename: Philip K
authors.initials: PK
authors.lastname: Liu
authors.forename: Christina H
authors.initials: CH
authors.lastname: Liu
authors.forename: Kenneth D
authors.initials: KD
authors.lastname: Bloch
authors.forename: Fumito
authors.initials: F
authors.lastname: Ichinose
mesh_terms: D000280:Administration, Inhalation; D000388:Air; D000818:Animals; D017209:Apoptosis; D001794:Blood Pressure; D001921:Brain / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D016887:Cardiopulmonary Resuscitation; D053148:Caspase 3 / Q000378:metabolism; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D004058:Diffusion; D004789:Enzyme Activation / Q000187:drug effects; D006162:Guanylate Cyclase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D006323:Heart Arrest / Q000401:mortality / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009420:Nervous System / Q000503:physiopathology; D009566:Nitrates / Q000097:blood; D009569:Nitric Oxide / Q000008:administration & dosage*; D009573:Nitrites / Q000097:blood; D012119:Respiration; D012995:Solubility; D015996:Survival Rate; D013997:Time Factors; D016277:Ventricular Function, Left; D016278:Ventricular Function, Right; D014867:Water / Q000378:metabolism
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D009566:Nitrates; D009573:Nitrites; D014867:Water; D009569:Nitric Oxide; D053148:Caspase 3; D006162:Guanylate Cyclase