Impaired peripheral endothelial function in severe idiopathic pulmonary hypertension correlates with the pulmonary vascular response to inhaled iloprost.
BACKGROUND
Pulmonary endothelial function is known to be impaired in subjects with idiopathic pulmonary arterial hypertension (IPAH), but peripheral endothelial dysfunction and its predictive value for pulmonary vasoreactivity have not been previously investigated.


METHODS
Measurements of peripheral endothelium-dependent and endothelium-independent vasoreactivity using flow-mediated dilation (FMD) and nitroglycerin-mediated dilation of the brachial artery were performed in 18 patients with severe IPAH (15 women; mean age 50 years [95% confidence interval 46-55 years], mean pulmonary artery pressure [PAP] 51 mm Hg [43-59 mm Hg], pulmonary vascular resistance [PVR] 1239 dyn s cm(-5) [861-1618 dyn s cm(-5)] at baseline) and in 36 age- and sex-matched controls. In patients with IPAH, acute pulmonary vasoreactivity was measured as pulmonary vascular response to inhaled iloprost (PVRII) during pulmonary catheterization.


RESULTS
Compared to controls, patients with IPAH demonstrated impaired peripheral endothelial function (FMD, 0.19 [0.07-0.31] vs 0.38 [0.30-0.44] mm among controls; P =.002). No such impairment was observed for nitroglycerin-mediated dilation (0.34 [0.23-0.46] vs 0.36 [0.20-0.51] mm among controls; P = .679). Among patients with IPAH, iloprost lowered mean PAP by 8.2 mm Hg (2.0-14.5 mm Hg) (P = .001) and PVR by 395 dyn s cm(-5) (109-680 dyn s cm(-5)) (P < .001). Subsequent analysis of the association between peripheral endothelial function and PVRII disclosed a correlation of FMD with the percent decrease in mean PAP (r = .65, P = .003) and PVR (r = 0.67, P = .002), in which patients with IPAH with the greatest PVRII also exhibited the highest FMD values.


CONCLUSIONS
Idiopathic pulmonary arterial hypertension is associated with peripheral endothelial dysfunction. Peripheral endothelium-dependent vasoreactivity correlates with the PVRII. It remains to be established if FMD has the potential as a clinical tool for noninvasive estimation of pulmonary vasoreactivity in IPAH.
Wolff
Birger
B
Department of Cardiology, Franz-Volhard-Klinik Berlin, Charitè Campus Buch, HELIOS Kliniken Berlin, Berlin, Germany. birger.wolff@helios-kliniken.de
Lodziewski
Sven
S
Bollmann
Tom
T
Opitz
Christian F
CF
Ewert
Ralf
R
D000280:Administration, Inhalation; D000328:Adult; D001916:Brachial Artery / Q000187:drug effects / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000503:physiopathology*; D016285:Iloprost / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D005996:Nitroglycerin / Q000494:pharmacology; D011652:Pulmonary Circulation / Q000187:drug effects*; D014655:Vascular Resistance / Q000187:drug effects*; D014664:Vasodilation / Q000187:drug effects*
D005996:Nitroglycerin; D016285:Iloprost