Residual pulmonary vasoreactivity to inhaled nitric oxide in patients withsevere obstructive pulmonary hypertension and Eisenmenger syndrome

Objective-To determine whether inhaled NO (iNO) can reduce pulmonary vascul ar resistance in adults with congenital heart disease and obstructive pulmo nary hypertension or Eisenmenger syndrome. Design-23 patients received graded doses of iNO. Pulmonary and systemic hae modynamic variables and circulating cyclic guanosine monophosphate (cGMP) c oncentrations were measured at baseline and after 20 and 80 ppm iNO. Patien ts were considered responders when total pulmonary resistance was reduced b y at least 20%, and rebound was defined as a greater than 10% increase in t otal 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 resp onse to 80 ppm iNO it decreased in six patients (29%, 95% CI 10% to 38%). S ystemic blood pressure did not change. Withdrawal resulted in rebound in th ree 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. Patien ts with predominant right to left shunting did not respond. In all patients cGMP increased from (mean (SD)) 28 (13) mu mol/l at baseline to 55 (30) an d 78 (44) mu mol/l after 20 and 80 ppm iNO (p < 0.05 v baseline). Conclusions-NO inhalation is safe and is associated with a dose dependent i ncrease in circulating cGMP concentrations. Pulmonary vasodilatation in res ponse 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.