title: Theoretical and experimental comparison of constant inspired concentration and pulsed delivery in NO therapy.
abstract: OBJECTIVE
  Inhaled NO therapy of artificially ventilated patients has been established as being based on constant inspired concentration of NO. In this study a new volumetrically controlled pulsed NO delivery mode is compared with the established concentration-based concept.
  
  
  METHODS
  To evaluate the relationship between NO delivery parameters, alveolar NO fraction, and patient uptake, a mathematical lung model was created where NO delivery can be simulated in varying ventilator settings, delivery modes, and lung properties. This model and the efficacy of pulsed delivery in inducing pulmonary capillary vasodilatation were examined experimentally.
  
  
  METHODS
  Animal laboratory, Department of Medical Sciences, Clinical Physiology.
  
  
  METHODS
  The experimental study was performed with nine pigs of mixed breed weighing 25-35 kg.
  
  
  METHODS
  The pigs were anaesthetised and artificially ventilated. Pulmonary vasoconstriction was induced by hypoxia. NO was delivered periodically in the various delivery modes.
  
  
  RESULTS
  In simulation, in all delivery modes the NO uptake was found to be dependent on the ventilator settings and the volume of the dead space. Measured from pulmonary artery pressure, the pulsed delivery was as effective in reducing the induced pulmonary vasoconstriction as the constant inspired concentration delivery. The amount of NO that could reduce the vasoconstriction back to baseline was 105 nmol x min(-1). By delivering in the early part of the inspiration, ambient contamination by the exhaust gas is avoided. The expired NO values obtained in the simulation and the experiments were equal. Based on the simulation, the alveolar NO fraction and the NO uptake depend on the ventilator settings and the dead space in both volumetric- and concentration-based delivery.
  
  
  CONCLUSIONS
  With pulsed delivery, a therapeutic effect comparable to constant inspired concentration delivery is achieved, NO gas is used more effectively, and environmental exhausts are reduced. The theoretical model shows that the NO delivery does not predict alveolar NO fraction and the NO uptake. However, it still remains an open question if the online measurement of these parameters would provide useful information, having added value in predicting and controlling the efficacy of the NO treatment.
authors.affiliation: Department of Medical Sciences, Clinical Physiology, Uppsala University, Sweden.
authors.forename: E
authors.initials: E
authors.lastname: Heinonen
authors.forename: M
authors.initials: M
authors.lastname: Högman
authors.forename: P
authors.initials: P
authors.lastname: Meriläinen
mesh_terms: D000818:Animals; D003198:Computer Simulation; D016503:Drug Delivery Systems; D008955:Models, Cardiovascular; D009569:Nitric Oxide / Q000008:administration & dosage* / Q000378:metabolism; D011650:Pulmonary Alveoli / Q000187:drug effects; D011669:Pulmonary Wedge Pressure / Q000187:drug effects; D012044:Regression Analysis; D012121:Respiration, Artificial; D015656:Respiratory Mechanics / Q000187:drug effects; D012138:Respiratory Therapy / Q000295:instrumentation* / Q000379:methods; D013552:Swine; D014665:Vasodilator Agents / Q000008:administration & dosage* / Q000378:metabolism
chemical_list: D014665:Vasodilator Agents; D009569:Nitric Oxide