Aerosolized PGE(1) PGI(2) and nitroprusside protect against vascular leakage in lung ischaemia-reperfusion

High permeability oedema is an important feature in lung injury secondary t o ischaemia-reperfusion. This study investigated the influence of aerosoliz ed prostaglandin E-1 (PGE(1)), prostaglandin I-2 (PGI(2)) and the nitric ox ide (NO)-donor, sodium nitroprusside (SNP) on microvascular harrier functio n in pulmonary ischaemia-reperfusion. Buffer-perfused rabbit lungs were exposed to 180 or 210 min of warm ischaem ia while maintaining anoxic ventilation and a positive intravascular pressu re. Reperfusion provoked a transient, mostly precapillary elevation of vascular resistance, followed by a severe increase of the capillary filtration coef ficient (Kfc) versus nonischaemic controls (3.17 +/- 0.34 versus 0.85 +/- 0 .05 cm(3) s(-1).cmH(2)O.g(-1).10(-4) after 30 min of reperfusion), and prog ressive oedema formation. Short-term aerosolization of SNP, PGE(1) or PGI(2 ) at the beginning of ischaemia largely suppressed the Kfc increase (1.36 /- 0.22, 1.32 +/- 0.23 and 1.32 +/- 0.22 cm(3).s(-1).cmH(2)O(-1).g(-1).10(- 4), respectively) and oedema formation. In contrast, application prior to r eperfusion was much less effective, with some reduction of Kfc increase by PGI(2) and SNP and no effect of PGE1 (1.79 +/- 0.31, 2.2 +/- 0.53 and 3.2 /- 0.05 cm(3).s(-1)cmH(2)O.g(-1).10(-4), respectively). Haemodynamics, incl uding microvascular pressure, were only marginally affected by the chosen d oses of aerosolized vasodilators. It is concluded that short-term aerosolization of prostaglandin E-1, prosta glandin I-2 and sodium nitroprusside at the onset of ischaemia is highly ef fective in maintaining endothelial barrier properties in pulmonary ischaemi a-reperfusion. This effect is apparently attributable to nonvasodilatory me chanisms exerted by these agents. Alveolar deposition of prostaglandins and /or nitric oxide donors by the aerosol technique may offer pulmonary protec tion in ischaemia-reperfusion injury.