Successful twenty-four-hour canine lung preservation with lazaroid U74500A

Background: Lipid peroxidation is known to contribute to ischemia- reperfusion injury. U74500A is a 21-aminosteroid (lazaroid) that prevents lipid peroxidation without corticoid side effects. We examined the effect of U74500A on lung preservation using a canine orthotopic single left lung transplantation model. Methods: Twelve adult mongrel dogs underwent left lung allotransplantation. The lungs of the donor dogs were flushed with University of Wisconsin solution (50 ml/kg). Six donor dogs were pretreated with U74500A (5 mg/kg intravenously) before preservation (group L, n = 6), whereas those dogs without pretreatment served as controls (group C, n = 6). Allografts were stored in University of Wisconsin solution for 24 hours at 1° C. Left single lung transplantations were performed by means of standard technique. Before reperfusion, recipients in group L received another dose of U74500A. Arterial blood gas analysis and hemodynamic measurements were made by occluding the right pulmonary artery to evaluate the transplanted left lung function at a inspired oxygen fraction of 1.0. Serum lipid peroxide level was measured after 2 hours of reperfusion. Results: Arterial oxygen tension, arterial carbon dioxide tension, and left pulmonary vascular resistance at 6 hours after reperfusion were significantly better in group L than in group C (arterial oxygen tension: 510 ± 66 and 219 ± 149 mm Hg; arterial carbon dioxide tension: 47 ± 16 and 68 ± 14 mm Hg; left pulmonary vascular resistance: 2412 ± 826 and 3904 ± 1251 dyn · sec/cm⁵, group L and group C, respectively). Serum lipid peroxide level was significantly lower in group L (0.25 ± 0.24 nmol/ml) than in group C (0.92 ± 0.53). Conclusions: The administration of U74500A prevented lipid peroxidation and preserved pulmonary allograft function after 24 hours of ischemia.