DONOR LIVER PROCUREMENT USING DBcAMP FROM CARDIAC-ARREST CADAVERS.

近年来，器官移植的日益频繁，导致心脏跳动尸体的供体器官严重短缺。从非心脏跳动的尸体器官捐赠已试图恢复这些情况，然而，它涉及一个长期的热缺血，这会导致第一功能障碍，然后结构变化，并最终细胞死亡。二丁酰cAMP（DBcAMP）具有高的膜通透性，维持细胞内cAMP浓度可提高器官的存活率。本研究评价了DBcAMP预处理对大鼠肝脏热缺血损伤的影响。在体重250-280 g的成年Wistar大鼠中，通过在心脏骤停后将其置于室温（22-25 ℃）下诱导热缺血性肝损伤。在不同时间的热缺血后，测定肝脏cAMP浓度、%ATP和台盼蓝阳性核比率。此外，转氨酶和内皮素（ET-1）释放到灌流液中进行了检查，在60分钟的Krebs-Henseleit溶液的隔离肝脏灌注。DBcAMP预处理的最佳剂量和时间分别为15 mg/kg和60 min。台盼蓝阳性细胞核比率、转氨酶和ET-1的释放数据显示，热缺血首先损害内皮细胞，然后损害肝细胞。DBcAMP预处理通过增加细胞内cAMP浓度和稳定内皮细胞和肝细胞的细胞膜来保护肝脏免受热缺血损伤。

Recent increasing frequency of organ transplantation has caused severe shortage of donor organ from heart-beating cadavers. Organ donation from nonheart-beating cadavers has been attempted to recover these situation, however, it involves a prolonged period of warm ischemia, which causes first functional impairment, then to structural changes, and ultimately to cell death. Dibutyryl cAMP (DBcAMP) has a high membrane permeability, and maintenance of the intracellular cAMP concentration may improve the viability of organs. In this study, the effect of DBcAMP pretreatment on warm ischemic injury of rat livers was evaluated. Warm ischemic liver injury was induced in adult Wistar rats weighing 250-280 g by leaving them at room temperature (22-25ﾟC) after cardiac arrest. The hepatic cAMP concentration, %ATP,and trypan blue-positive nuclear ratio were determined after different durations of warm ischemia. In addition, transaminase and endothelin (ET-1) release into the perfusate were examined during 60 min of isolated liver perfusion with Krebs-Henseleit solution. The optimal dose and time of DBcAMP pretreatment were determined to be 15 mg/kg and 60 min prior to warm ischemia, respectively. Data on the trypan blue-positive nuclear ratio, and the release of transaminases and ET-1 revealed that warm ischemia first damaged the endothelial cells and then the hepatocytes. DBcAMP pretreatment appeared to protect the liver from warm ischemic injury by increasing the intracellular cAMP concentration and stabilizing the cell membranes of endothelial cells and hepatocytes.