Protection against gas exchange abnormalities by pre-aerosolized PGE(1), iloprost and nitroprusside in lung ischemia-reperfusion

Background. Development of severe gas exchange abnormalities and respirator y failure is a major threat in lung transplantation. Methods, We used a model of ischemia-reperfusion injury in buffer-perfused rabbit lungs, with gas exchange conditions being analyzed in detail by the multiple inert gas elimination technique. A total of 150 min of warm ischem ia was performed, and anoxic ventilation and a positive intravascular press ure were maintained throughout the ischemic period. Results. Reperfusion provoked a transient, mostly precapillary pulmonary ar tery pressure elevation and progressive lung edema formation attributable t o increased capillary permeability. Severe ventilation-perfusion mismatch w ith predominance of shunt flow became apparent within minutes after onset o f reperfusion, 5 min-aerosolization maneuvers for alveolar deposition of pr ostaglandin E-1, the long-acting prostacyclin analogue iloprost or the nitr ic oxide donor agent sodium nitroprusside were undertaken at the onset of i schemia, All preaerosolized vasodilator agents markedly reduced the pulmona ry artery pressure elevation and the leakage response upon reperfusion, Mos t impressively, maintenance of physiological ventilation-perfusion matching was achieved by these maneuvers, and the development of shunt flow was lar gely suppressed. Conclusions. Preischemic alveolar deposition of PGE(1), iloprost, and sodiu m nitroprusside by aerosol technique is highly effective in conserving norm al pulmonary hemodynamics, microvascular integrity, and physiological gas e xchange conditions upon reperfusion. This approach may offer as new strateg y for maintenace of pulmonary function in lung transplantation.