Zardaverine and aerosolised iloprost in a model of acute respiratory failure.
Article Details
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Schermuly RT, Leuchte H, Ghofrani HA, Weissmann N, Rose F, Kohstall M, Olschewski H, Schudt C, Grimminger F, Seeger W, Walmrath D
Zardaverine and aerosolised iloprost in a model of acute respiratory failure.
Eur Respir J. 2003 Aug;22(2):342-7.
- PubMed ID
- 12952271 [ View in PubMed]
- Abstract
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 approximately 2 to 58%, as assessed by the multiple inert gas elimination technique). Aerosolisation of PGI2 (in total 1.05 microg x kg(-1) for 15 min caused a decrease in pulmonary artery pressure (Ppa) and a limitation of maximum shunt flow to approximately 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 microg x 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 microg x kg(-1)) for 15 min caused a more sustained decrease in Ppa, some enhanced reduction of oedema formation as compared with PGI2 and a decrease in shunt flow to approximately 32%. Most impressively, when combined with subthreshold zardaverine, iloprost suppressed oedema formation to <15% and shunt flow to approximately 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.
DrugBank Data that Cites this Article
- Drug Targets
Drug Target Kind Organism Pharmacological Action Actions Iloprost cAMP-specific 3',5'-cyclic phosphodiesterase 4A Protein Humans UnknownInducerDetails Iloprost cAMP-specific 3',5'-cyclic phosphodiesterase 4B Protein Humans UnknownInducerDetails Iloprost cAMP-specific 3',5'-cyclic phosphodiesterase 4C Protein Humans UnknownInducerDetails Iloprost cAMP-specific 3',5'-cyclic phosphodiesterase 4D Protein Humans UnknownInducerDetails