利用拉扎罗类药物U74500A成功实现犬肺24小时保存。

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

作者信息

Tanoue Y, Morita S, Ochiai Y, Zhang Q W, Hisahara M, Miyamoto K, Nishida T, Kawachi Y, Tominaga R, Yasui H

机构信息

Department of Cardiovascular Surgery, Faculty of Medicine, Kyushu University, Fukuoka, Japan.

出版信息

J Heart Lung Transplant. 1996 Jan;15(1 Pt 1):43-50.

PMID:8820082

Abstract

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.

摘要

背景

已知脂质过氧化作用会导致缺血再灌注损伤。U74500A是一种21 -氨基类固醇（拉扎罗类药物），可防止脂质过氧化且无皮质激素副作用。我们使用犬原位单左肺移植模型研究了U74500A对肺保存的影响。

方法

12只成年杂种犬接受左肺同种异体移植。供体犬的肺用威斯康星大学溶液（50 ml/kg）冲洗。6只供体犬在保存前静脉注射U74500A（5 mg/kg）（L组，n = 6），而未进行预处理的犬作为对照组（C组，n = 6）。同种异体移植物在1℃的威斯康星大学溶液中保存24小时。通过标准技术进行左单肺移植。在再灌注前，L组的受体接受另一剂U74500A。通过阻断右肺动脉进行动脉血气分析和血流动力学测量，以在吸入氧分数为1.0时评估移植的左肺功能。再灌注2小时后测量血清脂质过氧化物水平。

结果

再灌注6小时后，L组的动脉血氧张力、动脉血二氧化碳张力和左肺血管阻力明显优于C组（动脉血氧张力：510±66和219±149 mmHg；动脉血二氧化碳张力：47±16和68±14 mmHg；左肺血管阻力：2412±826和3904±1251 dyn·sec/cm5，分别为L组和C组）。L组的血清脂质过氧化物水平（0.25±0.24 nmol/ml）明显低于C组（0.92±0.53）。