AEROSOLIZED PROSTACYCLIN AND ILOPROST IN SEVERE PULMONARY-HYPERTENSION

Objective: To compare the effects of aerosolization of prostacyclin an d its stable analog iloprost with those of nasal oxygen, inhaled nitri c oxide, and intravenous prostacyclin on hemodynamics and gas exchange in patients with severe pulmonary hypertension. Design: Open uncontro lled trial. Setting: Justus-Liebig-University, Giessen, Germany. Patie nts: 4 patients with primary pulmonary hypertension and 2 patients wit h severe pulmonary hypertension associated with calcinosis, the Raynau d phenomenon, esophageal dysfunction, sclerodactyly, and telangiectasi a (the CREST syndrome). All were classified as New York Heart Associat ion class III or class IV. Intervention: Short-term applications of O- 2, inhaled nitric oxide, intravenous prostacyclin, aerosolized prostac yclin, and aerosolized iloprost during repeated catheter investigation of the right side of the heart within a 1-month period. One patient h ad long-term therapy with inhaled iloprost. Results: Aerosolized prost acyclin 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 ar terial pressure was only slightly affected. The responses lasted for 1 0 to 30 minutes after inhalation was terminated. Aerosolized iloprost had an identical efficacy profile but was associated with a longer dur ation of the pulmonary vasodilatory effect (60 min to 120 min). In com parison, intravenous prostacyclin reduced pulmonary vascular resistanc e with corresponding efficacy but produced a more pronounced decline i n systemic artery pressure and no clinically significant decrease in p ulmonary artery pressure. Nitric oxide and O-2 were less potent pulmon ary vasodilators in these patients. In one patient, 1 year of therapy with aerosolized iloprost (100 mu g/d in six aerosol doses) resulted i n sustained efficacy of the inhaled vasodilator regimen and clinical i mprovement. Conclusion: Aerosolization of prostacyclin or its stable a nalog iloprost causes selective pulmonary vasodilatation, increases ca rdiac 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.