title: Combined effects of NO inhalation and intravenous PGF2 alpha on pulmonary circulation and gas exchange in an ovine ARDS model.
abstract: OBJECTIVE
  Inhalation of nitric oxide (NO) selectively dilates pulmonary vessels in well-ventilated regions. Prostaglandin F2 alpha (PGF2 alpha) is a vasoconstrictor and is reported to enhance hypoxic pulmonary vasoconstriction. The objective of this study was to examine whether the combination of intravenous PGF2 alpha and inhaled NO in ARDS lungs has a beneficial effect on oxygenation.
  
  
  METHODS
  We investigated the effect of intravenous PGF2 alpha infusion (0.05-10.0 micrograms/kg per min) with and without NO inhalation (60 ppm) on the hemodynamics and gas exchange in an ovine ARDS model, examining the pulmonary artery pressure versus the flow plot by varying cardiac output.
  
  
  RESULTS
  After lung lavage, NO inhalation reduced the mean pulmonary arterial pressure (MPAP) by decreasing the zero-flow pressure intercept from 10.6 +/- 3.8 (mean +/- SD) to 8.5 +/- 3.8 mmHg (p < 0.05) with no significant change in slope. NO inhalation improved PaO2 from 56 +/- 12 to 84 +/- 38 mmHg (p < 0.005) and reduced pulmonary shunt from 65 +/- 5 to 53 +/- 8% (Qs/Qt) (p < 0.001). The dose-dependent effects of PGF2 alpha infusion were: (1) increased MPAP attributed to an increased slope in pulmonary artery pressure-flow plot; (2) decreased cardiac index; (3) decreased Qs/Qt with unchanged PaO2. The dose-dependent decrease in Qs/Qt after PGF2 alpha infusion was attributed to the decreased cardiac output.
  
  
  CONCLUSIONS
  It is suggested that inhalation of NO reduced the critical vascular pressure near alveoli without affecting upstream vessels, while infused PGF2 alpha constricted the larger upstream pulmonary artery vessels without appreciably affecting the critical pressure. Inhalation of NO into well-ventilated lung areas shifted perfusion to well-oxygenated areas, and there was no supplemental shift in blood flow by adding an infusion of PGF2 alpha.
authors.affiliation: Department of Anesthesia, Harvard Medical School at Massachusetts General Hospital, Boston 02114, USA.
authors.forename: H
authors.initials: H
authors.lastname: Kobayashi
authors.forename: N
authors.initials: N
authors.lastname: Tanaka
authors.forename: M
authors.initials: M
authors.lastname: Winkler
authors.forename: W M
authors.initials: WM
authors.lastname: Zapol
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D001784:Blood Gas Analysis; D015237:Dinoprost / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D007262:Infusions, Intravenous; D009569:Nitric Oxide / Q000627:therapeutic use*; D011652:Pulmonary Circulation / Q000187:drug effects*; D011659:Pulmonary Gas Exchange / Q000187:drug effects*; D012128:Respiratory Distress Syndrome / Q000188:drug therapy* / Q000503:physiopathology; D012756:Sheep
chemical_list: D009569:Nitric Oxide; D015237:Dinoprost