Effects of adrenomedullin inhalation on hemodynamics and exercise capacity in patients with idiopathic pulmonary arterial hypertension.
BACKGROUND
Adrenomedullin (AM) is a potent pulmonary vasodilator peptide. However, whether intratracheal delivery of aerosolized AM has beneficial effects in patients with idiopathic pulmonary arterial hypertension remains unknown. Accordingly, we investigated the effects of AM inhalation on pulmonary hemodynamics and exercise capacity in patients with idiopathic pulmonary arterial hypertension.


RESULTS
Acute hemodynamic responses to inhalation of aerosolized AM (10 microg/kg body wt) were examined in 11 patients with idiopathic pulmonary arterial hypertension during cardiac catheterization. Cardiopulmonary exercise testing was performed immediately after inhalation of aerosolized AM or placebo. The work rate was increased by 15 W/min until the symptom-limited maximum, with breath-by-breath gas analysis. Inhalation of AM produced a 13% decrease in mean pulmonary arterial pressure (54+/-3 to 47+/-3 mm Hg, P<0.05) and a 22% decrease in pulmonary vascular resistance (12.6+/-1.5 to 9.8+/-1.3 Wood units, P<0.05). However, neither systemic arterial pressure nor heart rate was altered. Inhalation of AM significantly increased peak oxygen consumption during exercise (peak o(2), 14.6+/-0.6 to 15.7+/-0.6 mL. kg(-1). min(-1), P<0.05) and the ratio of change in oxygen uptake to that in work rate (Deltao(2)/DeltaW ratio, 6.3+/-0.4 to 7.0+/-0.5 mL. min(-1). W(-1), P<0.05). These parameters remained unchanged during placebo inhalation.


CONCLUSIONS
Inhalation of AM may have beneficial effects on pulmonary hemodynamics and exercise capacity in patients with idiopathic pulmonary arterial hypertension.
Nagaya
Noritoshi
N
Department of Internal Medicine, National Cardiovascular Center, 5-7-1 Fujishirodai, Suita, Osaka 565-8565, Japan. nagayann@hsp.ncvc.go.jp
Kyotani
Shingo
S
Uematsu
Masaaki
M
Ueno
Kazuyuki
K
Oya
Hideo
H
Nakanishi
Norifumi
N
Shirai
Mikiyasu
M
Mori
Hidezo
H
Miyatake
Kunio
K
Kangawa
Kenji
K
D000280:Administration, Inhalation; D053607:Adrenomedullin; D000328:Adult; D017079:Exercise Tolerance / Q000187:drug effects*; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D006976:Hypertension, Pulmonary / Q000097:blood / Q000503:physiopathology*; D008168:Lung / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D010101:Oxygen Consumption / Q000187:drug effects; D010455:Peptides / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D011651:Pulmonary Artery / Q000187:drug effects / Q000503:physiopathology; D012123:Pulmonary Ventilation / Q000187:drug effects
D010455:Peptides; D053607:Adrenomedullin