Pulmonary flow reserve in children with idiopathic pulmonary arterial hypertension: implications for diagnosis and therapy.
OBJECTIVE
Endothelial dysfunction is likely to contribute to the pathogenesis of idiopathic Pulmonary Arterial Hypertension (iPAH). We hypothesize that there are different patterns of endothelial cell function, which we studied in 17 children with iPAH.


RESULTS
Pulmonary flow reserve was determined by acetylcholine infusion into segmental pulmonary arteries utilizing quantitative angiography and intra-arterial Doppler flow wire. Depending on the reactivity of the pulmonary to systemic arterial pressure ratio to short-term oxygen and intravenous epoprostenol or aerosolized iloprost responders and nonresponders were classified. In 7 responders to oxygen-prostanoid administration the pressure ratio decreased from 0.9 +/- 0.2 to 0.31 +/- 0.11 (p = 0.01), the mean pulmonary flow reserve showed an excessive increase to 3.6 +/- 2.0 (p = 0.01) after infusion of acetylcholine. In 10 non-responders the pressure ratios remained unchanged during oxygen-prostanoid testing. 4 of 5 patients without any effect to acetylcholine died despite long-term epoprostenol treatment. The other 5 nonresponders to oxygen-prostanoid showed an impaired but significant increase of the pulmonary flow reserve of 1.6 +/- 1.1 (p = 0.01). 2 of these patients did not only improve clinically, but regained vascular reactivity by additional therapy with sildenafil.


CONCLUSIONS
Endothelial reactivity in iPAH is either extensive, impaired or absent. Acetylcholine infusion casts a light on the pathogenesis and has implications for therapy.
Zimmermann
R
R
Paediatric Heart Center, Justus-Liebig University, Feulgenstrasse 12, D-35385 Giessen, Germany.
Kreuder
J
J
Michel-Behnke
I
I
Voelkel
Norbert F
NF
Schranz
Dietmar
D
D000109:Acetylcholine / Q000627:therapeutic use; D000293:Adolescent; D001794:Blood Pressure / Q000502:physiology; D002648:Child; D002675:Child, Preschool; D042783:Endothelial Cells / Q000378:metabolism; D011464:Epoprostenol / Q000627:therapeutic use; D006439:Hemodynamics; D006801:Humans; D006976:Hypertension, Pulmonary / Q000175:diagnosis* / Q000628:therapy*; D016285:Iloprost / Q000627:therapeutic use; D007223:Infant; D008168:Lung / Q000098:blood supply*; D010879:Piperazines; D011687:Purines; D012039:Regional Blood Flow; D000068677:Sildenafil Citrate; D013450:Sulfones; D014665:Vasodilator Agents / Q000627:therapeutic use*
D010879:Piperazines; D011687:Purines; D013450:Sulfones; D014665:Vasodilator Agents; D000068677:Sildenafil Citrate; D011464:Epoprostenol; D016285:Iloprost; D000109:Acetylcholine