REDUCED ISCHEMIA-REPERFUSION INJURY WITH ISOPROTERENOL IN NON-HEART-BEATING DONOR LUNGS

Transplantation of lungs retrieved from non-heart-beating donors could expand the donor pool. Recent studies suggest that the ischemia-reper fusion injury (IRI) to the lung can be attenuated by increasing intrac ellular cAMP concentrations. The purpose of this study was to determin e the effect of IRI on capillary permeability, as measured by K-fc, in lungs retrieved from nan-heart-beating donors and reperfused with or without isoproterenol (iso), Using an in situ isolated perfused lung m odel, lungs were retrieved from non-heart-beating donor rats ventilate d with O-2 or not at varying intervals after death. The lungs were rep erfused with or without iso (10 mu M). K-fc, lung viability, and pulmo nary hemodynamics were measured, and tissue levels of adenine nucleoti des and cAMP were measured by HPLC. Iso-reperfusion decreased K-fc sig nificantly (P < 0.05) compared to non-iso-reperfused groups at all pos tmortem ischemic times, irrespective of preharvest ventilation status. Pulmonary arterial pressures and resistances increased and venous res istances decreased with iso-reperfusion. Total adenine nucleotide (TAN ) levels correlated with K-fc in non-iso-reperfused (r = 0.65) and iso -perfused (r = 0.84) lungs. cAMP levels increased significantly with i so-reperfusion. cAMP levels correlated with K-fc (r = 0.87) in iso-rep erfused lungs. Iso-reperfusion of lungs retrieved from non-heart-beati ng donor rats results in decreased capillary permeability and increase d lung tissue cAMP levels, Pharmacologic augmentation of tissue TAN an d cAMP levels may further ameliorate the increased capillary permeabil ity seen in lungs retrieved from non-heart-beating donors. (C) 1997 Ac ademic Press.