Improvement of pulmonary graft after storage for twenty-four hours by in vivo administration of lazaroid U74389G: functional and morphologic analysis.

Background: We examined the effects of in vivo administration of a potent 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 system or reperfused after cold storage (4 degrees C) for 24 hours in the University of Wisconsin solution with (n = 7) or without (n = 8) lazaroid. 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, and blood gases were assessed during the perfusion period. Lipid peroxidation in the lung tissue was assayed with the thiobarbituric acid-reactive product, malondialdehyde. Histologic evaluation was performed with light microscopic and transmission electron microscopic analyses.

Results: All lungs in the University of Wisconsin solution group (24-hour storage without lazaroid) failed within 1 hour of reperfusion. Lungs in control and University of Wisconsin solution + lazaroid group survived the 2-hour perfusion period. University of Wisconsin solution + lazaroid group showed significantly better arterial oxygen tension values relative to those in the University of Wisconsin solution group (control, 85.2 +/- 1.9; University of Wisconsin solution, 53.9 +/- 3.2 [p < 0.05 versus control group and University of Wisconsin solution + lazaroid]; University of Wisconsin solution + lazaroid, 74.8 +/- 1.4; arterial oxygen tension (mm Hg) at 30 minutes). Lipid peroxide in University of Wisconsin solution + lazaroid group was significantly lower than that of the University of Wisconsin solution group (65.0 +/- 5.0 versus 495 +/- 105 nmol malondialdehyde/gm wet lung tissue; p < 0.01). Transmission electron microscopic analysis showed that University of Wisconsin solution + lazaroid group significantly attenuated lung damage when compared with University of Wisconsin solution group.

Conclusion: Administration of lazaroids in vivo before organ harvest and in situ at the onset of the reperfusion enhances lung preservation in this model.