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身体的供体器官严重短缺。从无心脏跳动的身体中捐献器官试图恢复这些情况，然而，它涉及到长时间的热缺血，这首先导致功能障碍，然后导致结构改变，最终导致细胞死亡。二丁酰cAMP(DBcAMP)具有较高的膜通透性，维持细胞内cAMP浓度可能提高器官的存活率。本研究观察了DBcAMP对大鼠肝脏热缺血损伤的影响。成年Wistar大鼠心脏骤停后置于室温(22~25ﾟC)，造成大鼠热缺血性肝损伤。测定不同时间热缺血后肝脏cAMP浓度、%ATP和台盼蓝阳性核比率。此外，在Krebs-Henseleit液灌流60min期间，检测转氨酶和内皮素(ET-1)释放到灌流液中的情况。确定DBcAMP的最佳剂量和时间分别为热缺血前15 mg/kg和60min。台盼蓝阳性核比率、转氨酶和ET-1释放的数据显示，热缺血首先损害内皮细胞，然后是肝细胞。DBcAMP可通过增加细胞内cAMP浓度，稳定内皮细胞和肝细胞的细胞膜，从而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.