title: An animal model of response and nonresponse to inhaled nitric oxide in endotoxin-induced lung injury.
abstract: OBJECTIVE
  Oxygenation may be improved in 40 to 60% of ARDS patients by inhalation of nitric oxide (NO). We have studied the response to inhaled NO in porcine acute lung injury 4 h and 6 h after onset of a 2-h endotoxin infusion (30 microg/kg/h), hypothesizing that a responder may change to a nonresponder over time and with progression of lung injury.
  
  
  METHODS
  Animal study.
  
  
  METHODS
  Experimental laboratory in a university hospital.
  
  
  METHODS
  We studied eight pigs under general anesthesia (mean weight, 26.2 kg) receiving mechanical ventilation adjusted to normocapnia, with a fraction of inspired oxygen (FIO(2)) of 0.5 to 1.0. Blood gases, endotoxin concentration, and central hemodynamics were measured hourly, and ventilation-perfusion (/) relationships were assessed by multiple inert gas elimination technique before and after inhalation of NO. NO was delivered at 40 ppm for 10 min at 4 h and 6 h of endotoxin exposure.
  
  
  RESULTS
  Seven of eight pigs were responders to NO at 4 h, defined as a > or = 20% increase in oxygenation index (PaO(2)/FIO(2)) [223 +/- 43 to 330 +/- 56 mm Hg; p = 0.001]. The same pigs exhibited a > or = 20% fall in mean pulmonary artery pressure (39.4 +/- 2.2 to 30.0 +/- 2.1 mm Hg; p < 0.001). The response correlated to the perfusion to "normal /" regions (r = - 0.82) and negatively to shunt and dead space ventilation (r = 0.76 and r = 0.87, respectively). At 6 h, seven of eight pigs were nonresponders, despite unaltered hemodynamics and gas exchange. Correlations at 4 h between physiologic variables and response to NO were abolished. The logarithmic SDs of the perfusion distribution, a measure of the degree of / mismatch, increased significantly from 4 to 6 h (p = 0.04).
  
  
  CONCLUSIONS
  Response to inhaled NO is abolished over time in endotoxin-induced ARDS pig lungs. The response seems to be related to the degree of / mismatch, which may indicate an important role of hypoxic pulmonary vasoconstriction.
authors.affiliation: Department of Clinical Physiology, University Hospital, Uppsala, Sweden.
authors.forename: H
authors.initials: H
authors.lastname: Maurenbrecher
authors.forename: M
authors.initials: M
authors.lastname: Lamy
authors.forename: G
authors.initials: G
authors.lastname: Deby-Dupont
authors.forename: P
authors.initials: P
authors.lastname: Frascarolo
authors.forename: G
authors.initials: G
authors.lastname: Hedenstierna
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D004195:Disease Models, Animal; D004731:Endotoxins; D006439:Hemodynamics / Q000502:physiology; D007262:Infusions, Intravenous; D008168:Lung / Q000503:physiopathology; D008171:Lung Diseases / Q000139:chemically induced*; D009569:Nitric Oxide / Q000008:administration & dosage*; D012128:Respiratory Distress Syndrome / Q000503:physiopathology*; D013552:Swine
chemical_list: D004731:Endotoxins; D009569:Nitric Oxide