Residual pulmonary vasoreactivity to inhaled nitric oxide in patients with severe obstructive pulmonary hypertension and Eisenmenger syndrome.
OBJECTIVE
To determine whether inhaled NO (iNO) can reduce pulmonary vascular resistance in adults with congenital heart disease and obstructive pulmonary hypertension or Eisenmenger syndrome.


METHODS
23 patients received graded doses of iNO. Pulmonary and systemic haemodynamic variables and circulating cyclic guanosine monophosphate (cGMP) concentrations were measured at baseline and after 20 and 80 ppm iNO. Patients were considered responders when total pulmonary resistance was reduced by at least 20%, and rebound was defined as a greater than 10% increase in total pulmonary resistance upon withdrawal from iNO.


RESULTS
In response to 20 ppm iNO, total pulmonary resistance decreased in four patients (18%, 95% confidence interval (CI), 2% to 34%), while in response to 80 ppm iNO it decreased in six patients (29%, 95% CI 10% to 38%). Systemic blood pressure did not change. Withdrawal resulted in rebound in three patients (16%, 95% CI 0% to 32%) after cessation of 20 ppm iNO, and in six patients (35%, 95% CI 12% to 58%) after cessation of 80 ppm iNO. Patients with predominant right to left shunting did not respond. In all patients cGMP increased from (mean (SD)) 28 (13) micromol/l at baseline to 55 (30) and 78 (44) micromol/l after 20 and 80 ppm iNO (p < 0.05 v baseline).


CONCLUSIONS
NO inhalation is safe and is associated with a dose dependent increase in circulating cGMP concentrations. Pulmonary vasodilatation in response to iNO was observed in 29% of patients and was influenced by baseline pulmonary haemodynamics. Responsiveness to acute iNO may identify patients with advanced obstructive pulmonary hypertension and Eisenmenger syndrome who could benefit from sustained vasodilator treatment.
Budts
W
W
Department of Cardiology, University Hospital Gasthuisberg, Herestraat 49, B-3000 Leuven, Belgium. werner.budts@uz.kuleuven.ac.be
Van Pelt
N
N
Gillyns
H
H
Gewillig
M
M
Van De Werf
F
F
Janssens
S
S
D000280:Administration, Inhalation; D000328:Adult; D016001:Confidence Intervals; D006152:Cyclic GMP / Q000378:metabolism; D004541:Eisenmenger Complex / Q000150:complications / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000187:drug effects; D005260:Female; D006330:Heart Defects, Congenital / Q000150:complications / Q000503:physiopathology*; D006801:Humans; D006976:Hypertension, Pulmonary / Q000150:complications / Q000503:physiopathology*; D008297:Male; D009569:Nitric Oxide / Q000008:administration & dosage*; D014655:Vascular Resistance / Q000187:drug effects*; D014665:Vasodilator Agents / Q000008:administration & dosage*
D014665:Vasodilator Agents; D009569:Nitric Oxide; D006152:Cyclic GMP