Reduced Ischemia–Reperfusion Injury with Isoproterenol in Non-Heart-Beating Donor Lungs

Abstract

Transplantation of lungs retrieved from non-heart-beating donors could expand the donor pool. Recent studies suggest that the ischemia–reperfusion injury (IRI) to the lung can be attenuated by increasing intracellular cAMP concentrations. The purpose of this study was to determine the effect of IRI on capillary permeability, as measured byKfc, in lungs retrieved from non-heart-beating donors and reperfused with or without isoproterenol (iso). Using anin situisolated perfused lung model, lungs were retrieved from non-heart-beating donor rats ventilated with O2or not at varying intervals after death. The lungs were reperfused with or without iso (10 μM).Kfc, lung viability, and pulmonary hemodynamics were measured, and tissue levels of adenine nucleotides and cAMP were measured by HPLC. Iso-reperfusion decreasedKfcsignificantly (P< 0.05) compared to non-iso-reperfused groups at all postmortem ischemic times, irrespective of preharvest ventilation status. Pulmonary arterial pressures and resistances increased and venous resistances decreased with iso-reperfusion. Total adenine nucleotide (TAN) levels correlated withKfcin non-iso-reperfused (r= 0.65) and iso-perfused (r= 0.84) lungs. cAMP levels increased significantly with iso-reperfusion. cAMP levels correlated withKfc(r= 0.87) in iso-reperfused lungs. Iso-reperfusion of lungs retrieved from non-heart-beating donor rats results in decreased capillary permeability and increased lung tissue cAMP levels. Pharmacologic augmentation of tissue TAN and cAMP levels may further ameliorate the increased capillary permeability seen in lungs retrieved from non-heart-beating donors.