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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.

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