title: 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 by Kfc, in lungs retrieved from non-heart-beating donors and reperfused with or without isoproterenol (iso). Using an in situ isolated perfused lung model, lungs were retrieved from non-heart-beating donor rats ventilated with O2 or not at varying intervals after death. The lungs were reperfused with or without iso (10 microM). Kfc, lung viability, and pulmonary hemodynamics were measured, and tissue levels of adenine nucleotides and cAMP were measured by HPLC. Iso-reperfusion decreased Kfc significantly (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 with Kfc in non-iso-reperfused (r = 0.65) and iso-perfused (r = 0.84) lungs. cAMP levels increased significantly with iso-reperfusion. cAMP levels correlated with Kfc (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.
authors.affiliation: Department of Surgery, University of North Carolina School of Medicine, Chapel Hill 27599, USA.
authors.forename: D R
authors.initials: DR
authors.lastname: Jones
authors.forename: S C
authors.initials: SC
authors.lastname: Hoffmann
authors.forename: M
authors.initials: M
authors.lastname: Sellars
authors.forename: T M
authors.initials: TM
authors.lastname: Egan
mesh_terms: D000227:Adenine Nucleotides / Q000378:metabolism; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D002199:Capillary Permeability; D002470:Cell Survival; D000242:Cyclic AMP / Q000378:metabolism; D006439:Hemodynamics; D007545:Isoproterenol / Q000627:therapeutic use*; D016040:Lung Transplantation / Q000379:methods*; D008297:Male; D009926:Organ Preservation / Q000379:methods*; D010100:Oxygen / Q000378:metabolism; D011188:Potassium / Q000378:metabolism; D011652:Pulmonary Circulation; D051381:Rats; D017207:Rats, Sprague-Dawley; D018343:Receptors, Adrenergic, beta-2 / Q000502:physiology; D015427:Reperfusion Injury / Q000517:prevention & control*; D014019:Tissue Donors; D014882:Water-Electrolyte Balance
chemical_list: D000227:Adenine Nucleotides; D000318:Adrenergic beta-Agonists; D018343:Receptors, Adrenergic, beta-2; D000242:Cyclic AMP; D007545:Isoproterenol; D011188:Potassium; D010100:Oxygen