The effect of normothermic recirculation is mediated by ischemic preconditioning in NHBD liver transplantation
The effect of normothermic recirculation is mediated by ischemic preconditioning in NHBD liver transplantation
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DOI：
10.1111/j.1600-6143.2005.01052.x
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发表时间：
2005-10-01
影响因子：
8.8
通讯作者：
García-Valdecasas, JC
中科院分区：
文献类型：
--
作者：
Net, M;Valero, R;García-Valdecasas, JC
我们已经评估了肝脏预适应介质的参与，在无心跳供体（NHBD）猪肝移植模型中，常温再循环（NR）过程中腺苷（adenosine）、腺苷A1和腺苷A2受体（adenosine A1和adenosine A2 receptor）的变化，热缺血（WI）20 min后应用NR可逆转NHBD肝移植相关的致死性损伤（达到5天存活率并降低谷胱甘肽S-转移酶（GST）、天冬氨酸转氨酶（AST）和透明质酸（HA））。测量腺苷，我们发现在NR期间，肝腺苷水平升高，黄嘌呤水平降低。阻断A_2受体后，NR的作用消失，而阻断A_1受体则进一步保护肝脏。此外，阻断A2可改善NR期间的肝脏灌注，而阻断A1则可降低肝脏灌注。研究表明，NR通过维持足够的腺苷和黄嘌呤水平而具有预处理效应。在NR期间，腺苷通过A2激活保护肝脏，并通过A1激活损害肝脏，尽管同时刺激两种受体会产生明显的有益作用。本文还讨论了NR机制与其他预适应介质如cAMP和一氧化氮合成的可能关系。
We have evaluated the involvement of hepatic preconditioning mediators (adenosine, adenosine A1 and A2 receptors) during normothermic recirculation (NR) in a model of liver transplantation from non-heart-beating donor (NHBD) pigs.Application of NR after 20 min of warm ischemia (WI) reversed the lethal injury associated with transplantation of NHBD livers (achieving 5-day survival and diminishing glutathione S-transferase (GST), aspartate aminotransferase (AST) and hyaluronic acid (HA)).Adenosine administration prior to WI simulated the effect of NR. Measuring adenosine, we found that during NR, hepatic adenosine levels increased and xanthine levels decreased. Then when we blocked A2 receptors the effect of NR was abolished, whereas the blocking of A1 receptors further protected the liver. Furthermore, A2 blocking improved hepatic perfusion during NR whereas A1 blocking reduced it.The study suggests that NR has a preconditioning effect by maintaining adequate adenosine and xanthine levels. During NR, adenosine protects the liver through A2 activation and damages it through A1 activation although simultaneous stimulation of both receptors exerts a clear beneficial effect. The possible relation of NR mechanism with other preconditioning mediators such as cAMP and nitric oxide synthesis are discussed.