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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; 22(2):342-347 Doi: 10.1183/09031936.03.00093802 [OPEN ACCESS]
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Co-authors Med Uni Graz: Olschewski Horst
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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.
Find related publications in this database (using NLM MeSH Indexing): 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid -; Administration, Inhalation -; Animals -; Antihypertensive Agents - administration and dosage; Disease Models, Animal - administration and dosage; Dose-Response Relationship, Drug - administration and dosage; Drug Therapy, Combination - administration and dosage; Epoprostenol - administration and dosage; Female - administration and dosage; Iloprost - administration and dosage; Infusions, Intravenous - administration and dosage; Male - administration and dosage; Phosphodiesterase Inhibitors - administration and dosage; Pyridazines - administration and dosage; Rabbits - administration and dosage; Respiratory Distress Syndrome, Adult - chemically induced; Vasodilator Agents - administration and dosage
Find related publications in this database (Keywords): iloprost; multiple inert gas elimination technique; phosphodiesterase; prostacyclin; rabbit; zardaverine