Aerosolized prostacyclin and iloprost in severe pulmonary hypertension.
OBJECTIVE
To compare the effects of aerosolization of prostacyclin and its stable analog iloprost with those of nasal oxygen, inhaled nitric oxide, and intravenous prostacyclin on hemodynamics and gas exchange in patients with severe pulmonary hypertension.


METHODS
Open uncontrolled trial.


METHODS
Justus-Liebig-University, Giessen Germany.


METHODS
4 patients with primary pulmonary hypertension and 2 patients with severe pulmonary hypertension associated with calcinosis, the Raynaud phenomenon, esophageal dysfunction, sclerodactyly, and telangiectasia (the CREST syndrome). All were classified as New York Heart Association class III or class IV.


METHODS
Short-term applications of O2, inhaled nitric oxide, intravenous prostacyclin, aerosolized prostacyclin, and aerosolized iloprost during repeated catheter investigation of the right side of the heart within a 1-month period. One patient had long-term therapy with inhaled iloprost.


RESULTS
Aerosolized prostacyclin decreased pulmonary artery pressure in 6 patients from (mean +/- SE) 62.3 +/- 4.1 mm Hg to 50.8 +/- 5.5 mm Hg and reduced pulmonary vascular resistance from 1721 +/- 253 dyne/s cm-5 to 1019 +/- 203 dyne/s cm-5, and it increased cardiac output from 2.75 +/- 0.21 L/min to 4.11 +/- 0.54 L/min, mixed venous oxygen saturation from 51.1% +/- 3/4% to 66.3% +/- 4.1% and arterial oxygen saturation from 90.6% +/- 2.7% to 93.8% +/- 23% (P<0.05 for all changes). Mean systemic arterial pressure was only slightly affected. The responses lasted for 10 to 30 minutes after inhalation was terminated. Aerosolized iloprost had an identical efficacy profile but was associated with a longer duration of the pulmonary vasodilatory effect (60 min to 120 min). In comparison, intravenous prostacyclin reduced pulmonary vascular resistance with corresponding efficacy but produced a more pronounced decline in systemic artery pressure and no clinically significant decrease in pulmonary artery pressure. Nitric oxide and O2 were less potent pulmonary vasodilators in these patients. In one patient, 1 year of therapy with aerosolized iloprost (100 microgram/d in six aerosol doses) resulted in sustained efficacy of the inhaled vasodilator regimen and clinical improvement.


CONCLUSIONS
Aerosolization of prostacyclin or its stable analog iloprost causes selective pulmonary vasodilatation, increases cardiac output, and improves venous and arterial oxygenation in patients with severe pulmonary hypertension. Thus, it may offer a new strategy for treatment of this disease.
Olschewski
H
H
Department of Medicine, Justus-Liebig-University, Giessen, Germany.
Walmrath
D
D
Schermuly
R
R
Ghofrani
A
A
Grimminger
F
F
Seeger
W
W
D000328:Adult; D000336:Aerosols; D000959:Antihypertensive Agents / Q000008:administration & dosage*; D011464:Epoprostenol / Q000008:administration & dosage*; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D006976:Hypertension, Pulmonary / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D016285:Iloprost / Q000008:administration & dosage*; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000627:therapeutic use; D010102:Oxygen Inhalation Therapy; D014665:Vasodilator Agents / Q000008:administration & dosage*
D000336:Aerosols; D000959:Antihypertensive Agents; D014665:Vasodilator Agents; D009569:Nitric Oxide; D011464:Epoprostenol; D016285:Iloprost