IMPROVEMENT OF PULMONARY GRAFT AFTER STORAGE FOR 24 HOURS BY IN-VIVO ADMINISTRATION OF LAZAROID U74389G - FUNCTIONAL AND MORPHOLOGIC ANALYSIS

Background: We examined the effects of in vivo administration of a pot ent inhibitor of iron-dependent lipid peroxidation, lazaroid U74389G, on lung preservation. Methods: Lungs isolated from Sprague-Dawley rats (n = 23) were either immediately reperfused after removal (control, n = 8) for 2 hours by means of an isolated, pulsatile blood perfusion s ystem or reperfused after cold storage (4 degrees C) for 24 hours in t he University of Wisconsin solution with (n = 7) or without (n = 8) la zaroid. The lazaroid group had in vivo infusion of lazaroid U74389G (6 mg/kg) before lung harvest plus addition to the perfusate (50 mu mol/ L) at the onset of reperfusion. Routine aerodynamics, hemodynamics, an d blood gases were assessed during the perfusion period. Lipid peroxid ation in the lung tissue was assayed with the thiobarbituric acid-reac tive product, malondialdehyde. Histologic evaluation was performed wit h light microscopic and transmission electron microscopic analyses. Re sults: All lungs in the University of Wisconsin solution group (24-hou r storage without lazaroid) failed within 1 hour of reperfusion. Lungs in-control and University of Wisconsin solution + lazaroid group-surv ived the 2-hour perfusion period. University of Wisconsin solution + l azaroid group showed significantly better arterial oxygen tension valu es relative to those in the University of Wisconsin solution group (co ntrol, 85.2 +/- 1.9; University of Wisconsin solution, 53.9 +/- 3.2 [p < 0.05 versus control group and University of Wisconsin solution + la zaroid]; University of Wisconsin solution + lazaroid, 74.8 +/- 1.4; ar terial oxygen tension (mm Hg) at 30 minutes). Lipid peroxide in Univer sity of Wisconsin solution + lazaroid. group was significantly lower t han that of the University of Wisconsin solution group (65.0 +/- 5.0 v ersus 495 +/- 105 nmol malondialdehyde/gm wet lung tissue; p < 0.01). Transmission electron microscopic analysis showed that University of W isconsin solution + lazaroid group significantly attenuated lung damag e when compared with University of Wisconsin solution group. Conclusio n: Administration of lazaroids in vivo before organ harvest and in sit u at the onset of the reperfusion enhances lung preservation in this m odel.