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(Circulation. 2001;103:544.)
© 2001 American Heart Association, Inc.

Clinical Investigation and Reports

Inhaled Nitric Oxide Versus Aerosolized Iloprost in Secondary Pulmonary Hypertension in Children With Congenital Heart Disease

Vasodilator Capacity and Cellular Mechanisms

Peter C. Rimensberger, MD; Isabelle Spahr-Schopfer, MD; Michel Berner, MD; Edgar Jaeggi, MD; Afksendiyos Kalangos, PhD, MD; Beat Friedli, MD; Maurice Beghetti, MD

From the Pediatric and Neonatal Critical Care Division (P.C.R., M. Berner) and the Pediatric Cardiology Unit (E.J., B.F., M. Beghetti), Hôpital des Enfants, and the Department of Pediatrics, the Pediatric Anesthesiology Unit, Department of Anesthesiology (I.S.-S.), and the Clinic for Cardiovascular Surgery (A.K.), University Hospital of Geneva, Switzerland.

Correspondence to Maurice Beghetti, MD, Pediatric Cardiology Unit, Hôpital des Enfants, Department of Pediatrics, University Hospital of Geneva, 6 Rue Willy-Donze, CH-1211 Geneva 14, Switzerland. E-mail Maurice.Beghetti{at}hcuge.ch

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.

Methods and 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.

Key Words: hypertension, pulmonary • heart defects, congenital • vasodilatation • nitric oxide • prostaglandins

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