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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 degrees 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 center dot 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.