Zardaverine and aerosolised iloprost in a model of acute respiratory failure.

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.

• Authors: R T Schermuly, H Leuchte, H A Ghofrani, N Weissmann, F Rose, M Kohstall, H Olschewski, C Schudt, F Grimminger, W Seeger, D Walmrath
• Journal: The European respiratory journal (Eur Respir J) Vol. 22 Issue 2 Pg. 342-7 (Aug 2003) ISSN: 0903-1936 [Print] England
• PMID: 12952271 (Publication Type: Journal Article)

Chemical References

• Antihypertensive Agents
• Phosphodiesterase Inhibitors
• Pyridazines
• Vasodilator Agents
• 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid
• Epoprostenol
• Iloprost
• zardaverine

Topics

• 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid
• Administration, Inhalation
• Animals
• Antihypertensive Agents (administration & dosage)
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Drug Therapy, Combination
• Epoprostenol (administration & dosage)
• Female
• Iloprost (administration & dosage)
• Infusions, Intravenous
• Male
• Phosphodiesterase Inhibitors (administration & dosage)
• Pyridazines (administration & dosage)
• Rabbits
• Respiratory Distress Syndrome (chemically induced, drug therapy)
• Vasodilator Agents (administration & dosage)