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(Circulation. 2004;109:351-356.)
© 2004 American Heart Association, Inc.

Clinical Investigation and Reports

Effects of Adrenomedullin Inhalation on Hemodynamics and Exercise Capacity in Patients With Idiopathic Pulmonary Arterial Hypertension

Noritoshi Nagaya, MD; Shingo Kyotani, MD; Masaaki Uematsu, MD; Kazuyuki Ueno, PhD; Hideo Oya, MD; Norifumi Nakanishi, MD; Mikiyasu Shirai, MD; Hidezo Mori, MD; Kunio Miyatake, MD; Kenji Kangawa, PhD

From the Department of Internal Medicine, National Cardiovascular Center, Osaka (N. Nagaya, S.K., H.O., N. Nakanishi, K.M.); the Cardiovascular Division, Kansai Rosai Hospital, Hyogo (M.U.); the Department of Pharmacy, National Cardiovascular Center, Osaka (K.U.); the Department of Cardiac Physiology, National Cardiovascular Center Research Institute, Osaka (M.S., H.M.); and the Department of Biochemistry, National Cardiovascular Center Research Institute, Osaka (K.K.), Japan.

Correspondence to Noritoshi Nagaya, MD, Department of Internal Medicine, National Cardiovascular Center, 5-7-1 Fujishirodai, Suita, Osaka 565-8565, Japan. E-mail nagayann{at}hsp.ncvc.go.jp

Received February 3, 2003; de novo received July 28, 2003; revision received October 15, 2003; accepted October 19, 2003.

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.

Methods and Results— Acute hemodynamic responses to inhalation of aerosolized AM (10 µg/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 O₂, 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 (O₂/W 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.

Key Words: peptides • hypertension, pulmonary • respiration • exercise • hemodynamics

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