Inhaled nitric oxide versus aerosolized iloprost in secondary pulmonary hypertension in children with congenital heart disease: vasodilator capacity and cellular mechanisms.
BACKGROUND
Inhaled nitric oxide (iNO) has been used to assess the vasodilator 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 (release of cGMP or cAMP, respectively), we compared the pulmonary vasodilator capacity of each.


RESULTS
A total of 15 children with congenital heart disease and PHT who had elevated pulmonary vascular resistance (preoperative, n=10; immediately postoperative, n=5) were first given 20 ppm of iNO for 10 minutes; then, after baseline values were reached again, they were given aerosolized iloprost at 25 ng. kg(-1). min(-1) for another 10 minutes. Finally, iNO and iloprost were given simultaneously for 10 minutes. With iNO, the pulmonary vascular resistance and systemic vascular resistance ratio decreased from 0.48+/-0.38 to 0.27+/-0.16 (P:<0.001). Similarly, iloprost decreased 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 from 17.6+/-11.9 to 34.7+/-21.4 nmol/L during iNO (P:<0.01), and plasma cAMP increased 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 pulmonary vascular resistance through an increase in cGMP or cAMP, respectively. However, the combination of both vasodilators failed to prove more potent than either substance alone. Aerosolized iloprost might be an alternative to iNO for early testing of vascular reactivity and for the postoperative treatment of acute PHT.
Rimensberger
P C
PC
Pediatric and Neonatal Critical Care Division, Hôpital des Enfants, University Hospital of Geneva, Switzerland.
Spahr-Schopfer
I
I
Berner
M
M
Jaeggi
E
E
Kalangos
A
A
Friedli
B
B
Beghetti
M
M
D000280:Administration, Inhalation; D000336:Aerosols; D000704:Analysis of Variance; D002648:Child; D002675:Child, Preschool; D000242:Cyclic AMP / Q000097:blood; D006152:Cyclic GMP / Q000097:blood; D006330:Heart Defects, Congenital / Q000150:complications*; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D016285:Iloprost / Q000008:administration & dosage*; D007223:Infant; D008168:Lung / Q000098:blood supply / Q000187:drug effects / Q000503:physiopathology; D009569:Nitric Oxide / Q000008:administration & dosage*; D011652:Pulmonary Circulation / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects; D014665:Vasodilator Agents / Q000008:administration & dosage*
D000336:Aerosols; D014665:Vasodilator Agents; D009569:Nitric Oxide; D000242:Cyclic AMP; D006152:Cyclic GMP; D016285:Iloprost