{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,25]],"date-time":"2025-02-25T05:11:50Z","timestamp":1740460310477,"version":"3.37.3"},"reference-count":30,"publisher":"European Respiratory Society (ERS)","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Eur Respir J"],"accepted":{"date-parts":[[2003,3,24]]},"published-print":{"date-parts":[[2003,8]]},"abstract":"<jats:p>In this study, the impact of aerosolised prostacyclin (PGI<jats:sub>2<\/jats:sub>) 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.<\/jats:p><jats:p>In perfused rabbit lungs, continuous infusion of the thromboxane\u2010A<jats:sub>2<\/jats:sub>\u2010mimetic U46619 provoked pulmonary hypertension, accompanied by progressive lung oedema formation and severe ventilation-perfusion mismatch with predominance of shunt flow (increasing from \u223c2 to 58%, as assessed by the multiple inert gas elimination technique). Aerosolisation of PGI<jats:sub>2<\/jats:sub>(in total 1.05\u2005\u00b5g\u00b7kg<jats:sup>\u22121<\/jats:sup>) for 15\u2005min caused a decrease in pulmonary artery pressure (<jats:italic>P<\/jats:italic><jats:sub>pa<\/jats:sub>) and a limitation of maximum shunt flow to \u223c37%. When nebulised PGI<jats:sub>2<\/jats:sub>was combined with subthreshold intravascular zardaverine, which did not affect pulmonary haemodynamics<jats:italic>per se<\/jats:italic>, the duration of the PGI<jats:sub>2<\/jats:sub>effect was increased. Aerosolisation of 3\u2005\u00b5g\u00b7kg<jats:sup>\u22121<\/jats:sup>PGI<jats:sub>2<\/jats:sub>resulted in a transient decrease in<jats:italic>P<\/jats:italic>pa and a reduction in shunt flow. In the presence of subthreshold zardaverine, the effects of this PGI<jats:sub>2<\/jats:sub>dose were only marginally increased. Aerosolisation of iloprost (in total 0.7\u2005\u00b5g\u00b7kg<jats:sup>\u22121<\/jats:sup>) for 15\u2005min caused a more sustained decrease in<jats:italic>P<\/jats:italic><jats:sub>pa<\/jats:sub>, some enhanced reduction of oedema formation as compared with PGI<jats:sub>2<\/jats:sub>and a decrease in shunt flow to \u223c32%. Most impressively, when combined with subthreshold zardaverine, iloprost suppressed oedema formation to &lt;15% and shunt flow to \u223c8%.<\/jats:p><jats:p>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.<\/jats:p>","DOI":"10.1183\/09031936.03.00093802","type":"journal-article","created":{"date-parts":[[2003,7,29]],"date-time":"2003-07-29T21:02:12Z","timestamp":1059512532000},"page":"342-347","source":"Crossref","is-referenced-by-count":13,"title":["Zardaverine and aerosolised iloprost in a model of acute 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