Protection against gas exchange abnormalities by pre-aerosolized PGE1, iloprost and nitroprusside in lung ischemia-reperfusion.
BACKGROUND
Development of severe gas exchange abnormalities and respiratory 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 ischemia was performed, and anoxic ventilation and a positive intravascular pressure were maintained throughout the ischemic period.


RESULTS
Reperfusion provoked a transient, mostly precapillary pulmonary artery pressure elevation and progressive lung edema formation attributable to increased capillary permeability. Severe ventilation-perfusion mismatch with predominance of shunt flow became apparent within minutes after onset of reperfusion. 5 min-aerosolization maneuvers for alveolar deposition of prostaglandin E1, the long-acting prostacyclin analogue iloprost or the nitric oxide donor agent sodium nitroprusside were undertaken at the onset of ischemia. All preaerosolized vasodilator agents markedly reduced the pulmonary artery pressure elevation and the leakage response upon reperfusion. Most impressively, maintenance of physiological ventilation-perfusion matching was achieved by these maneuvers, and the development of shunt flow was largely suppressed.


CONCLUSIONS
Preischemic alveolar deposition of PGE1, iloprost, and sodium nitroprusside by aerosol technique is highly effective in conserving normal pulmonary hemodynamics, microvascular integrity, and physiological gas exchange conditions upon reperfusion. This approach may offer as new strategy for maintenace of pulmonary function in lung transplantation.
Löckinger
A
A
Department of Anesthesiology and Critical Care Medicine, Leopold-Franzens University, Innsbruck, Austria.
Schütte
H
H
Walmrath
D
D
Seeger
W
W
Grimminger
F
F
D000336:Aerosols; D000527:Alprostadil / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D005260:Female; D016285:Iloprost / Q000008:administration & dosage / Q000627:therapeutic use*; D008170:Lung Compliance / Q000187:drug effects; D008297:Male; D009599:Nitroprusside / Q000627:therapeutic use*; D011659:Pulmonary Gas Exchange / Q000187:drug effects*; D011817:Rabbits; D015427:Reperfusion Injury / Q000517:prevention & control*; D013997:Time Factors; D014665:Vasodilator Agents / Q000627:therapeutic use; D015430:Weight Gain / Q000187:drug effects
D000336:Aerosols; D014665:Vasodilator Agents; D009599:Nitroprusside; D000527:Alprostadil; D016285:Iloprost