Stadler Michaela, Nuyens Vincent, Seidel Laurence, Albert Adelin, Boogaerts Jean G
Department of Anesthesiology and Laboratory of Experimental Medicine (ULB 222 Unit), University Hospital Center, Charleroi, Belgium.
Anesthesiology. 2005 Nov;103(5):978-86. doi: 10.1097/00000542-200511000-00012.
Normothermic ischemia-reperfusion is a determinant in liver injury occurring during surgical procedures, ischemic state, and multiple organ failure. The preexisting nutritional status of the liver might contribute to the extent of tissue injury and primary nonfunction. The aim of this study was to determine the role of starvation on hepatic ischemia-reperfusion injury in normal rat livers.
Rats were randomly divided into two groups: one had free access to food, the other was fasted for 16 h. The portal vein was cannulated, and the liver was removed and perfused in a closed ex vivo system. Two modes of perfusion were applied in each series of rats, fed and fasting. In the ischemia-reperfusion mode, the experiment consisted of perfusion for 15 min, warm ischemia for 60 min, and reperfusion during 60 min. In the nonischemia mode, perfusion was maintained during the 135-min study period. Five rats were included in each experimental condition, yielding a total of 20 rats. Liver enzymes, potassium, glucose, lactate, free radicals, i.e., dienes and trienes, and cytochrome c were analyzed in perfusate samples. The proportion of glycogen in hepatocytes was determined in tissue biopsies.
Transaminases, lactate dehydrogenase, potassium, and free radical concentrations were systematically higher in fasting rats in both conditions, with and without ischemia. Cytochrome c was higher after reperfusion in the fasting rats. Glucose and lactate concentrations were greater in the fed group. The glycogen content decreased in both groups during the experiment but was markedly lower in the fasting rats.
In fed rats, liver injury was moderate, whereas hepatocytes integrity was notably impaired both after continuous perfusion and warm ischemia in fasting animals. Reduced glycogen store in hepatocytes may explain reduced tolerance.
常温下的缺血再灌注是手术过程、缺血状态及多器官功能衰竭期间肝脏损伤的一个决定因素。肝脏先前的营养状况可能会影响组织损伤程度及原发性无功能。本研究的目的是确定饥饿对正常大鼠肝脏缺血再灌注损伤的作用。
将大鼠随机分为两组：一组可自由进食，另一组禁食16小时。插入门静脉，取出肝脏并在封闭的离体系统中进行灌注。在每组喂食和禁食的大鼠中应用两种灌注模式。在缺血再灌注模式下，实验包括灌注15分钟、热缺血60分钟及再灌注60分钟。在非缺血模式下，在135分钟的研究期间持续灌注。每种实验条件下纳入5只大鼠，共20只大鼠。分析灌注液样本中的肝酶、钾、葡萄糖、乳酸、自由基（即二烯和三烯）及细胞色素c。在组织活检中测定肝细胞中糖原的比例。
无论有无缺血，禁食大鼠的转氨酶、乳酸脱氢酶、钾及自由基浓度均系统性地更高。禁食大鼠再灌注后细胞色素c更高。喂食组的葡萄糖和乳酸浓度更高。实验期间两组的糖原含量均下降，但禁食大鼠的糖原含量明显更低。
在喂食的大鼠中，肝脏损伤较轻，而在禁食动物中，连续灌注和热缺血后肝细胞完整性均明显受损。肝细胞中糖原储备减少可能解释了耐受性降低的原因。
