Inhaled nitric oxide versus aerosolized iloprost in secondary pulmonary hypertension in children with congenital heart disease - Vasodilator capacityand cellular mechanisms

Background-Inhaled nitric oxide (iNO) has been used to assess the vasodilat or capacity of the pulmonary vascular bed in children with congenital heart disease and elevated pulmonary vascular resistance. Inhaled iloprost is a pulmonary vasodilator for the long-term treatment of pulmonary hypertension (PHT). Because these 2 vasodilators act through different pathways (releas e of cGMP or cAMP, respectively), we compared the pulmonary vasodilator cap acity of each. Methods and Results-A total of 15 children with congenital heart disease an d PHT who had elevated pulmonary vascular resistance (preoperative, n = 10; immediately postoperative, n = 5) were first given 20 ppm of iNO for 10 mi nutes; then, after baseline values were reached again, they were given aero solized iloprost at 25 ng . kg(-1) . min(-1) for another 10 minutes. Finall y, iNO and iloprost were given simultaneously for 10 minutes. With iNO, the pulmonary vascular resistance and systemic vascular resistance ratio decre ased from 0.48 +/- 0.38 to 0.27 +/- 0.16 (P<0.001), Similarly, iloprost dec reased the ratio from 0.49+/-0.38 to 0.26+/-0.11 (P<0.05). The combination had no additional effect on the resistance ratio. Plasma cGMP increased fro m 17.6+/-11.9 to 34.7+/-21.4 nmol/L during iNO (P<0.01), and plasma cAMP in creased from 55.7+/-22.9 to 65.1+/-21.2 nmol/L during iloprost inhalation ( P<0.05). Conclusions-In children with PHT and congenital heart disease, both iNO and aerosolized iloprost are equally effective in selectively lowering pulmona ry vascular resistance through an increase in cGMP or cAMP, respectively. H owever, the combination of both vasodilators failed to prove more potent th an either substance alone. Aerosolized iloprost might be an alternative to iNO for early testing of vascular reactivity and for the postoperative trea tment of acute PHT.