title: Brief inhalation of nitric oxide increases resuscitation success and improves 7-day-survival after cardiac arrest in rats: a randomized controlled animal study.
abstract: BACKGROUND
  Inhaled nitric oxide (iNO) improves outcomes when given post systemic ischemia/reperfusion injury. iNO given during cardiopulmonary resuscitation (CPR) may therefore improve return of spontaneous circulation (ROSC) rates and functional outcome after cardiac arrest (CA).
  
  
  METHODS
  Thirty male Sprague-Dawley rats were subjected to 10 minutes of CA and at least 3 minutes of CPR. Animals were randomized to receive either 0 (n = 10, Control), 20 (n = 10, 20 ppm), or 40 (n = 10, 40 ppm) ppm iNO during CPR until 30 minutes after ROSC. A neurological deficit score was assessed daily for seven days following the experiment. On day 7, brains, hearts, and blood were sampled for histological and biochemical evaluation.
  
  
  RESULTS
  During CPR, 20 ppm iNO significantly increased diastolic arterial pressure (
  
  
  METHODS
  57 ± 5.04 mmHg; 20 ppm: 71.57 ± 57.3 mmHg, p < 0.046) and decreased time to ROSC (CONTROL: 842 ± 21 s; 20 ppm: 792 ± 5 s, (p = 0.02)). Thirty minutes following ROSC, 20 ppm iNO resulted in an increase in mean arterial pressure (
  
  
  METHODS
  83 ± 4 mmHg; 20 ppm: 98 ± 4 mmHg, p = 0.035), a less pronounced rise in lactate and inflammatory cytokine levels, and attenuated cardiac damage. Inhalation of NO at 20 ppm improved neurological outcomes in rats 2 to 7 days after CA and CPR. This translated into increases in 7 day survival (
  
  
  METHODS
  4; 20 ppm: 10; 40 ppm 6, (p ≤ 0.05 20 ppm vs CONTROL and 40 ppm).
  
  
  CONCLUSIONS
  Our study revealed that breathing NO during CPR markedly improved resuscitation success, 7-day neurological outcomes and survival in a rat model of VF-induced cardiac arrest and CPR. These results support the beneficial effects of NO inhalation after cardiac arrest and CPR.
authors.affiliation: Department of Anesthesiology, University Hospital RWTH Aachen, Pauwelsstr. 30, 52074, Aachen, Germany. abruecken@ukaachen.de.
authors.forename: Anne
authors.initials: A
authors.lastname: Brücken
authors.affiliation: Department of Anesthesiology, University Hospital RWTH Aachen, Pauwelsstr. 30, 52074, Aachen, Germany. mderwall@ukaachen.de.
authors.forename: Matthias
authors.initials: M
authors.lastname: Derwall
authors.affiliation: Department of Anesthesiology, University Hospital RWTH Aachen, Pauwelsstr. 30, 52074, Aachen, Germany. cbleilevens@ukaachen.de.
authors.forename: Christian
authors.initials: C
authors.lastname: Bleilevens
authors.affiliation: Department of Anesthesiology, University Hospital RWTH Aachen, Pauwelsstr. 30, 52074, Aachen, Germany. cstoppe@ukaachen.de.
authors.forename: Christian
authors.initials: C
authors.lastname: Stoppe
authors.affiliation: Department of Thoracic, Cardiac and Vascular Surgery, University Hospital RWTH Aachen, Pauwelsstr. 30, 52074, Aachen, Germany. agoetzenich@ukaachen.de.
authors.forename: Andreas
authors.initials: A
authors.lastname: Götzenich
authors.affiliation: Institute of Pathology, University Hospital RWTH Aachen, Pauwelsstr. 30, 52074, Aachen, Germany. ngaisa@ukaachen.de.
authors.forename: Nadine T
authors.initials: NT
authors.lastname: Gaisa
authors.affiliation: Institute for Neuropathology, University Hospital RWTH Aachen, Pauwelsstr. 30, 52074, Aachen, Germany. jweis@ukaachen.de.
authors.forename: Joachim
authors.initials: J
authors.lastname: Weis
authors.affiliation: Institute for Neuropathology, University Hospital RWTH Aachen, Pauwelsstr. 30, 52074, Aachen, Germany. knolte@ukaachen.de.
authors.forename: Kay Wilhelm
authors.initials: KW
authors.lastname: Nolte
authors.affiliation: Department of Anesthesiology, University Hospital RWTH Aachen, Pauwelsstr. 30, 52074, Aachen, Germany. rrossaint@ukaachen.de.
authors.forename: Rolf
authors.initials: R
authors.lastname: Rossaint
authors.affiliation: Anesthesia Center for Critical Care Research, Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, 55 Fruit Street, Boston, MA, 02114, USA. fichinose@mgh.harvard.edu.
authors.forename: Fumito
authors.initials: F
authors.lastname: Ichinose
authors.affiliation: Department of Anesthesiology, St. Vincenz Hospital Limburg, Auf dem Schafsberg, 65549, Limburg, Germany. m.fries@st-vincenz.de.
authors.forename: Michael
authors.initials: M
authors.lastname: Fries
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D001921:Brain / Q000473:pathology; D016887:Cardiopulmonary Resuscitation / Q000379:methods*; D004195:Disease Models, Animal; D006323:Heart Arrest / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D008297:Male; D009206:Myocardium / Q000473:pathology; D009569:Nitric Oxide / Q000008:administration & dosage / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016896:Treatment Outcome; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D014665:Vasodilator Agents; D009569:Nitric Oxide