Journal article

Publication year: 2003

Pages: 342-347

Journal: European Respiratory Journal

Volume number: 22

Issue number: 2

ISSN: 0903-1936

eISSN: 1399-3003

Open access status: Green

DOI Link: https://doi.org/10.1183/09031936.03.00093802

Publisher: European Respiratory Society

Abstract: 

In this study, the impact of aerosolised prostacyclin (PGI(2)) 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-A(2)-mimetic U46619 provoked pulmonary hypertension, accompanied by progressive lung oedema formation and severe ventilation-perfusion mismatch with predominance of shunt flow (increasing from similar to2 to 58%, as assessed by the multiple inert gas elimination technique). Aerosolisation of PGI(2) (in total 1.05 mug.kg(-1)) pulmonary artery pressure (P-pa) and a limitation of maximum shunt flow to similar to37%. When nebulised PGI(2) was combined with subthreshold intravascular zardaverine, which did not affect pulmonary haemodynamics per se, the duration of the PGI(2) effect was increased. Aerosolisation of 3 mug.kg(-1) PGI(2) resulted in a transient decrease in Ppa and a reduction in shunt flow. In the presence of subthreshold zardaverine, the effects of this PGI(2) dose were only marginally increased. Aerosolisation of iloprost (in total 0.7 mug.kg(-1)) for 15 min caused a more sustained decrease in P-pa, some enhanced reduction of oedema formation as compared with PGI(2) and a decrease in shunt flow to similar to32%. Most impressively, when combined with subthreshold zardaverine, iloprost suppressed oedema formation to <15% and shunt flow to similar 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.

Harvard Citation style: Schermuly, R., Leuchte, H., Ghofrani, H., Weissmann, N., Rose, F., Kohstall, M., et al. (2003) Zardaverine and aerosolised iloprost in a model of acute respiratory failure, European Respiratory Journal, 22(2), pp. 342-347. https://doi.org/10.1183/09031936.03.00093802

APA Citation style: Schermuly, R., Leuchte, H., Ghofrani, H., Weissmann, N., Rose, F., Kohstall, M., Olschewski, H., Schudt, C., Grimminger, F., Seeger, W., & Walmrath, D. (2003). Zardaverine and aerosolised iloprost in a model of acute respiratory failure. European Respiratory Journal. 22(2), 342-347. https://doi.org/10.1183/09031936.03.00093802