Lazaroid U74500A as an additive to University of Wisconsin solution for pulmonary grafts in the rat transplant model

R. Aeba, W. A. Killinger, R. J. Keenan, S. A. Yousem, I. Hamamoto, R. L. Hardesty, B. P. Griffith

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30 Citations (Scopus)


Lazaroids are a class of novel 21 aminosteroids. They have been reported to be potent inhibitors of lipid peroxidation, which is a major contributing factor to ischemia-reperfusion injury in the lung. A Lewis rat orthotopic left lung isotransplant model was used to investigate the effects of the lazaroid U74500A on pulmonary preservation. The heart-lung blocks of donor rats were flushed with and then stored in either standard University of Wisconsin solution or University of Wisconsin solution with 30 μmol/L of U74500A substituted for the dexamethasone. After 6 or 12 hours of cold storage at 0° C, the left lungs were transplanted into recipient rats and reperfused for 1 hour. Pulmonary function was assessed by measuring oxygen and carbon dioxide tensions in arterial blood after removal of the right lung. Lipid peroxide concentrations were measured as a thiobarbituric acid- reactive substance. Although arterial oxygen and carbon dioxide pressures and water content after 6 hours of preservation followed by reperfusion were similar in both the lazaroid and dexamethasone groups, lipid peroxide concentration was significantly higher in the dexamethasone group (0.88 ± 0.07 μmol/gm) than in the lazaroid group (0.54 ± 0.07 μmol/gm) (p < 0.01). After 12 hours of preservation, there were significant differences between the lazaroid and dexamethasone groups in arterial oxygen pressure (339 ± 70 vs 27 ± 3 mm Hg, p < 0.01), arterial carbon dioxide pressure (24.3 ± 2.7 vs 47.7 ± 7.0 mm Hg, p < 0.001), and lipid peroxide concentrations (0.69 ± 0.07 vs 1.30 ± 0.09 μmol/gm, p < 0.001). We conclude that addition of U74500A to the flush and storage solution enhances the preservation of the pulmonary graft in this transplant model.

Original languageEnglish
Pages (from-to)1333-1339
Number of pages7
JournalJournal of Thoracic and Cardiovascular Surgery
Issue number5
Publication statusPublished - 1992

ASJC Scopus subject areas

  • Surgery
  • Pulmonary and Respiratory Medicine
  • Cardiology and Cardiovascular Medicine


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