title: Inhaled nitric oxide improves transpulmonary blood flow and clinical outcomes after prolonged cardiac arrest: a large animal study.
abstract: BACKGROUND
  The probability to achieve a return of spontaneous circulation (ROSC) after cardiac arrest can be improved by optimizing circulation during cardiopulomonary resuscitation using a percutaneous left ventricular assist device (iCPR). Inhaled nitric oxide may facilitate transpulmonary blood flow during iCPR and may therefore improve organ perfusion and outcome.
  
  
  METHODS
  Ventricular fibrillation was electrically induced in 20 anesthetized male pigs. Animals were left untreated for 10 minutes before iCPR was attempted. Subjects received either 20 ppm of inhaled nitric oxide (iNO, n = 10) or 0 ppm iNO (Control, n = 10), simultaneously started with iCPR until 5 hours following ROSC. Animals were weaned from the respirator and followed up for five days using overall performance categories (OPC) and a spatial memory task. On day six, all animals were anesthetized again, and brains were harvested for neurohistopathologic evaluation.
  
  
  RESULTS
  All animals in both groups achieved ROSC. Administration of iNO markedly increased iCPR flow during CPR (iNO: 1.81 ± 0.30 vs
  
  
  METHODS
  1.64 ± 0.51 L/min, p < 0.001), leading to significantly higher coronary perfusion pressure (CPP) during the 6 minutes of CPR (25 ± 13 vs 16 ± 6 mmHg, p = 0.002). iNO-treated animals showed significantly lower S-100 serum levels thirty minutes post ROSC (0.26 ± 0.09 vs 0.38 ± 0.15 ng/mL, p = 0.048), as well as lower blood glucose levels 120-360 minutes following ROSC. Lower S-100 serum levels were reflected by superior clinical outcome of iNO-treated animals as estimated with OPC (3 ± 2 vs. 5 ± 1, p = 0.036 on days 3 to 5). Three out of ten iNO-treated, but none of the CONTROL animals were able to successfully participate in the spatial memory task. Neurohistopathological examination of vulnerable cerebral structures revealed a trend towards less cerebral lesions in neocortex, archicortex, and striatum in iNO-treated animals compared to CONTROLs.
  
  
  CONCLUSIONS
  In pigs resuscitated with mechanically-assisted CPR from prolonged cardiac arrest, the administration of 20 ppm iNO during and following iCPR improved transpulmonary blood flow, leading to improved clinical neurological outcomes.
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. aebeling@ukaachen.de.
authors.forename: Andreas
authors.initials: A
authors.lastname: Ebeling
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: 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: 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: Abiomed Europe GmbH, Neuenhofer Weg 3, D-52074, Aachen, Germany. cnix@abiomed.com.
authors.forename: Christoph
authors.initials: C
authors.lastname: Nix
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
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
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D006323:Heart Arrest / Q000188:drug therapy* / Q000503:physiopathology; D006353:Heart-Assist Devices; D008297:Male; D009569:Nitric Oxide / Q000008:administration & dosage / Q000627:therapeutic use*; D011652:Pulmonary Circulation / Q000187:drug effects* / Q000502:physiology; D065852:Spatial Memory; D013552:Swine; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D014665:Vasodilator Agents; D009569:Nitric Oxide