Published Online
on January 12, 2004

A more recent version of this article appeared on January 27, 2004

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Submitted on February 3, 2003
Revised on October 15, 2003
Accepted on October 19, 2003

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, and 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.

^* To whom correspondence should be addressed. E-mail: nagayann{at}hsp.ncvc.go.jp.

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 VO₂, 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 (VO₂/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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