title: Lazaroid U74500A as an additive to University of Wisconsin solution for pulmonary grafts in the rat transplant model.
abstract: 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 mumol/L of U74500A substituted for the dexamethasone. After 6 or 12 hours of cold storage at 0 degrees 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 mumol/gm) than in the lazaroid group (0.54 +/- 0.07 mumol/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 mumol/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.
authors.affiliation: Division of Cardiothoracic Surgery, University of Pittsburgh, Pa.
authors.forename: R
authors.initials: R
authors.lastname: Aeba
authors.forename: W A
authors.initials: WA
authors.lastname: Killinger
authors.forename: R J
authors.initials: RJ
authors.lastname: Keenan
authors.forename: S A
authors.initials: SA
authors.lastname: Yousem
authors.forename: I
authors.initials: I
authors.lastname: Hamamoto
authors.forename: R L
authors.initials: RL
authors.lastname: Hardesty
authors.forename: B P
authors.initials: BP
authors.lastname: Griffith
mesh_terms: D000241:Adenosine; D000493:Allopurinol; D000818:Animals; D001834:Body Water; D002245:Carbon Dioxide / Q000097:blood; D002314:Cardioplegic Solutions / Q000494:pharmacology*; D003080:Cold Temperature; D003907:Dexamethasone / Q000494:pharmacology; D005978:Glutathione; D007328:Insulin; D007511:Ischemia; D008054:Lipid Peroxides / Q000032:analysis / Q000037:antagonists & inhibitors*; D008168:Lung / Q000098:blood supply / Q000737:chemistry / Q000187:drug effects*; D008297:Male; D009926:Organ Preservation / Q000379:methods*; D019188:Organ Preservation Solutions; D010100:Oxygen / Q000097:blood; D011281:Pregnatrienes / Q000494:pharmacology* / Q000627:therapeutic use; D011887:Raffinose; D051381:Rats; D011917:Rats, Inbred Lew; D015427:Reperfusion Injury / Q000503:physiopathology / Q000517:prevention & control*; D012996:Solutions / Q000494:pharmacology*
chemical_list: D002314:Cardioplegic Solutions; D007328:Insulin; D008054:Lipid Peroxides; D019188:Organ Preservation Solutions; D011281:Pregnatrienes; D012996:Solutions; C055206:University of Wisconsin-lactobionate solution; D002245:Carbon Dioxide; D000493:Allopurinol; D003907:Dexamethasone; D005978:Glutathione; C053356:U 74500A; D000241:Adenosine; D011887:Raffinose; D010100:Oxygen