title: Inhaled nitric oxide reduction in systolic pulmonary artery pressure is less in patients with decreased left ventricular ejection fraction.
abstract: OBJECTIVE
  To assess whether inhaled nitric oxide decreases pulmonary artery pressure in patients with depressed left ventricular ejection fraction.
  
  
  METHODS
  Randomized, blinded, crossover clinical trial.
  
  
  METHODS
  Tertiary care university referral hospital.
  
  
  METHODS
  Thirty-three patients with pulmonary hypertension and left ventricular dysfunction or valvular heart disease were recruited by convenience.
  
  
  METHODS
  Systolic pulmonary artery pressure was measured by Doppler echocardiography during randomized inhalation of either 20 ppm or 40 ppm nitric oxide in 30% oxygen as well as during control periods without nitric oxide.
  
  
  RESULTS
  Systolic pulmonary artery pressure was significantly (P < 0.05) decreased with 20 ppm nitric oxide (53.4 +/- 13.9 mmHg) and 40 ppm nitric oxide (53.1 +/- 14.4 mmHg) compared with either initial control (55.8 +/- 15.3 mmHg) or terminal control (56.3 +/- 15.2 mmHg) values. The regression equation for the change in systolic pulmonary artery pressure (y) as predicted by the left ventricular ejection fraction (x) alone for 20 ppm nitric oxide was y = 13.8x-2.9; R2adj = 0.30, P < 0.0001. For 40 ppm nitric oxide alone, the regression equation was y = 16.3x-3.3; R2adj = 0.25, P < 0.0001. Left ventricular ejection fraction was the most explanatory independent variable in the multivariate equation for nitric oxide-induced change in systolic pulmonary artery pressure (R2 = 0.61, P = 0.0000). The change in systolic pulmonary artery pressure was -5.1 +/- 5.2 versus 0.8 +/- 4.9 mmHg (P < 0.0000) in patients with left ventricular ejection fractions greater than 0.25, and 0.25 or less, respectively.
  
  
  CONCLUSIONS
  These data imply that in patients with left ventricular ejection fraction of 0.25 or less, nitric oxide may not decrease systolic pulmonary artery pressure. Nitric oxide inhalation may result in a paradoxical increase in systolic pulmonary artery pressure in patients with severely depressed left ventricular ejection fraction. This effect would significantly limit the therapeutic role of nitric oxide in patients with severe heart failure.
authors.affiliation: College of Medicine, Department of Medicine, University of Saskatchewan, Saskatoon. cujecb@duke.usask.ca
authors.forename: B
authors.initials: B
authors.lastname: Cujec
authors.forename: T
authors.initials: T
authors.lastname: Hurst
authors.forename: R
authors.initials: R
authors.lastname: McCuaig
authors.forename: D
authors.initials: D
authors.lastname: Antecol
authors.forename: I
authors.initials: I
authors.lastname: Mayers
authors.forename: D
authors.initials: D
authors.lastname: Johnson
mesh_terms: D000280:Administration, Inhalation; D000368:Aged; D018592:Cross-Over Studies; D015150:Echocardiography, Doppler; D005260:Female; D006349:Heart Valve Diseases / Q000503:physiopathology*; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D009569:Nitric Oxide / Q000008:administration & dosage*; D013318:Stroke Volume / Q000502:physiology; D014665:Vasodilator Agents / Q000008:administration & dosage*; D018487:Ventricular Dysfunction, Left / Q000503:physiopathology*
chemical_list: D014665:Vasodilator Agents; D009569:Nitric Oxide