title: Aerosolized PGE1, PGI2 and nitroprusside protect against vascular leakage in lung ischaemia-reperfusion.
abstract: High permeability oedema is an important feature in lung injury secondary to ischaemia-reperfusion. This study investigated the influence of aerosolized prostaglandin E1 (PGE1), prostaglandin I2 (PCI2) and the nitric oxide (NO)-donor, sodium nitroprusside (SNP) on microvascular barrier function in pulmonary ischaemia-reperfusion. Buffer-perfused rabbit lungs were exposed to 180 or 210 min of warm ischaemia while maintaining anoxic ventilation and a positive intravascular pressure. Reperfusion provoked a transient, mostly precapillary elevation of vascular resistance, followed by a severe increase of the capillary filtration coefficient (Kfc) versus nonischaemic controls (3.17+/-0.34 versus 0.85+/-0.05 cm3 x s(-1) cmH2O(-1) x g(-1) x 10(-4) after 30 min of reperfusion), and progressive oedema formation. Short-term aerosolization of SNP, PGE1 or PGI2 at the beginning of ischaemia largely suppressed the Kfc increase (1.36+/-0.22, 1.32+/-0.23 and 1.32+/-0.22 cm3 x s(-1) x cmH2O(-1) x g(-1) x 10(-4), respectively) and oedema formation. In contrast, application prior to reperfusion was much less effective, with some reduction of Kfc increase by PGI2 and SNP and no effect of PGE, (1.79+/-0.31, 2.2+/-0.53 and 3.2+/-0.05 cm3 x s(-1) x cmH2O(-1) x g(-1) x 10(-4), respectively). Haemodynamics, including microvascular pressure, were only marginally affected by the chosen doses of aerosolized vasodilators. It is concluded that short-term aerosolization of prostaglandin E1, prostaglandin I2 and sodium nitroprusside at the onset of ischaemia is highly effective in maintaining endothelial barrier properties in pulmonary ischaemia-reperfusion. This effect is apparently attributable to nonvasodilatory mechanisms exerted by these agents. Alveolar deposition of prostaglandins and/or nitric oxide donors by the aerosol technique may offer pulmonary protection in ischaemia-reperfusion injury.
authors.affiliation: Dept of Internal Medicine, Justus-Liebig University, Giessen, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Schütte
authors.forename: A
authors.initials: A
authors.lastname: Löckinger
authors.forename: W
authors.initials: W
authors.lastname: Seeger
authors.forename: F
authors.initials: F
authors.lastname: Grimminger
mesh_terms: D000336:Aerosols; D000527:Alprostadil / Q000494:pharmacology*; D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects*; D011464:Epoprostenol / Q000494:pharmacology*; D007511:Ischemia / Q000503:physiopathology; D008168:Lung / Q000098:blood supply*; D008833:Microcirculation / Q000187:drug effects / Q000503:physiopathology; D009330:Nebulizers and Vaporizers; D009599:Nitroprusside / Q000494:pharmacology*; D011654:Pulmonary Edema / Q000503:physiopathology; D011817:Rabbits; D015427:Reperfusion Injury / Q000503:physiopathology*; D014655:Vascular Resistance / Q000187:drug effects / Q000502:physiology
chemical_list: D000336:Aerosols; D009599:Nitroprusside; D011464:Epoprostenol; D000527:Alprostadil