title: Hypoxic pulmonary vasoconstriction in nonventilated lung areas contributes to differences in hemodynamic and gas exchange responses to inhalation of nitric oxide.
abstract: BACKGROUND
  Enhancement of hypoxic pulmonary vasoconstriction (HPV) in nonventilated lung areas by almitrine increases the respiratory response to inhaled nitric oxide (NO) in patients with acute respiratory distress syndrome (ARDS). Therefore the authors hypothesized that inhibition of HPV in nonventilated lung areas decreases the respiratory effects of NO.
  
  
  METHODS
  Eleven patients with severe ARDS treated by venovenous extracorporeal lung assist were studied. Patients' lungs were ventilated at a fraction of inspired oxygen (F[I(O2)]) of 1.0. By varying extracorporeal blood flow, mixed venous oxygen tension (P[O2]; partial oxygen pressure in mixed venous blood [PV(O2)]) was adjusted randomly to four levels (means, 47, 54, 64 and 84 mmHg). Extracorporeal gas flow was adjusted to prevent changes in mixed venous carbon dioxide tension [PV(CO2)]). Hemodynamic and gas exchange variables were measured at each level before, during, and after 15 ppm NO.
  
  
  RESULTS
  Increasing PV(O2) from 47 to 84 mmHg resulted in a progressive decrease in lung perfusion pressure (PAP-PAWP; P < 0.05) and pulmnonary vascular resistance index (PVRI; P < 0.05) and in an increase in intrapulmonary shunt (Q[S]/Q[T]; P < 0.05). PV(CO2) and cardiac index did not change. Whereas the NO-induced reduction in PAP-PAWP was smaller at high PV(O2), NO-induced decrease in Q(S)/Q(T) was independent of baseline PV(O2). In response to NO, arterial P(O2) increased more and arterial oxygen saturation increased less at high compared with low PV(O2).
  
  
  CONCLUSIONS
  In patients with ARDS, HPV in nonventilated lung areas modifies the hemodynamic and respiratory response to NO. The stronger the HPV in nonventilated lung areas the more pronounced is the NO-induced decrease in PAP-PAWP. In contrast, the NO-induced decrease in Q(S)/Q(T) is independent of PV(O2) over a wide range of PV(O2) levels. The effect of NO on the arterial oxygen tension varies with the level of PV(O2) by virtue of its location on the oxygen dissociation curve.
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, University of Freiburg, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Benzing
authors.forename: G
authors.initials: G
authors.lastname: Mols
authors.forename: T
authors.initials: T
authors.lastname: Brieschal
authors.forename: K
authors.initials: K
authors.lastname: Geiger
mesh_terms: D000280:Administration, Inhalation; D000328:Adult; D015199:Extracorporeal Membrane Oxygenation; D005260:Female; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D000860:Hypoxia / Q000503:physiopathology*; D008168:Lung / Q000098:blood supply / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000008:administration & dosage*; D010100:Oxygen / Q000008:administration & dosage / Q000097:blood / Q000502:physiology; D010477:Perfusion; D011652:Pulmonary Circulation / Q000187:drug effects*; D011659:Pulmonary Gas Exchange / Q000187:drug effects*; D012128:Respiratory Distress Syndrome / Q000503:physiopathology* / Q000628:therapy*; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*
chemical_list: D009569:Nitric Oxide; D010100:Oxygen