HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Permissions Request Permissions Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (7) Citing Articles via Google Scholar Google Scholar Articles by Schermuly, R.T. Articles by Walmrath, D. Search for Related Content PubMed PubMed Citation Articles by Schermuly, R.T. Articles by Walmrath, D.

Zardaverine and aerosolised iloprost in a model of acute respiratoryfailure

¹ Dept of Internal Medicine, Justus-Liebig-University, Giessen, and ² Altana Pharma, Constance, Germany

CORRESPONDENCE: R.T. Schermuly, Zentrum fürInnere Medizin, Justus-Liebig-Universität Giessen, Klinikstrasse 36, 35392 Giessen, Germany. Fax: 49 6419942419. E-mail: ralph.schermuly@innere.med.uni-giessen.de

Keywords: iloprost, multiple inert gas elimination technique, phosphodiesterase, prostacyclin, rabbit, zardaverine

Received: October 14, 2002
Accepted March 24, 2003

In this study, the impact of aerosolised prostacyclin (PGI₂) and iloprost in the absence or presence of subthreshold intravascular doses of the dual-selective phosphodiesterase-3/4 inhibitor zardaverine was investigated in an experimental model of acute respiratory failure.

In perfused rabbit lungs, continuous infusion of the thromboxane-A₂-mimetic U46619 provoked pulmonary hypertension, accompanied by progressive lung oedema formation and severe ventilation-perfusion mismatch with predominance of shunt flow (increasing from 2 to 58%, as assessed by the multiple inert gas elimination technique). Aerosolisation of PGI₂ (in total 1.05 µg·kg^–1) for 15 min caused a decrease in pulmonary artery pressure (P_pa) and a limitation of maximum shunt flow to 37%. When nebulised PGI₂ was combined with subthreshold intravascular zardaverine, which did not affect pulmonary haemodynamics per se, the duration of the PGI₂ effect was increased. Aerosolisation of 3 µg·kg^–1 PGI₂ resulted in a transient decrease in Ppa and a reduction in shunt flow. In the presence of subthreshold zardaverine, the effects of this PGI₂ dose were only marginally increased. Aerosolisation of iloprost (in total 0.7 µg·kg^–1) for 15 min caused a more sustained decrease in P_pa, some enhanced reduction of oedema formation as compared with PGI₂ and a decrease in shunt flow to 32%. Most impressively, when combined with subthreshold zardaverine, iloprost suppressed oedema formation to <15% and shunt flow to 8%.

In conclusion, combined use of aerosolised iloprost and subthreshold systemic phosphodiesterase-3/4 inhibitor may result in selective intrapulmonary vasodilation, a reduction in oedema formation and an improvement in ventilation-perfusion matching in acute respiratory failure.

This article has been cited by other articles:

				H. H. Leuchte, T. Meis, M. El-Nounou, J. Michalek, and J. Behr Inhalation of endothelin receptor blockers in pulmonary hypertension Am J Physiol Lung Cell Mol Physiol, April 1, 2008; 294(4): L772 - L777. [Abstract] [Full Text] [PDF]

				R. Dembinski, W. Brackhahn, D. Henzler, A. Rott, R. Bensberg, R. Kuhlen, and R. Rossaint Cardiopulmonary effects of iloprost in experimental acute lung injury Eur. Respir. J., January 1, 2005; 25(1): 81 - 87. [Abstract] [Full Text] [PDF]