Lei D X, Peng C H, Peng S Y, Jiang X C, Wu Y L, Shen H W
Department of Surgery, Zhongnan Hospital, Wuhan University School of Medicine, Wuhan 430071, Hubei Province, China.
World J Gastroenterol. 2001 Oct;7(5):713-7. doi: 10.3748/wjg.v7.i5.713.
To evaluate the effects of varying ischemic durations on cirrhotic liver and to determine the safe upper limit of repeated intermittent hepatic inflow occlusion.
Hepatic ischemia in cirrhotic rats was induced by clamping the common pedicle of left and median lobes after non-ischemic lobes resection. The cirrhotic rats were divided into six groups according to the duration and form of vascular clamping: sham occlusion (SO), intermittent occlusion for 10 (IO-10), 15(IO-15), 20(IO-20) and 30(IO-30) minutes with 5 minutes of reflow and continuous occlusion for 60 minutes (CO-60). All animals received a total duration of 60 minutes of hepatic inflow occlusion. Liver viability was investigated in relation of hepatic adenylate energy charge (EC). Triphenyltetrazollum chloride (TTC) reduction activities were assayed to qualitatively evaluate the degree of irreversible hepatocellular injury. The biochemical and morphological changes were also assessed and a 7-day mortality was observed.
At 60 minutes after reperfusion following a total of 60 minutes of hepatic inflow occlusion, EC values in IO-10 (0.749 +/- 0.012) and IO-15 (0.699 +/- 0.002) groups were rapidly restored to that in SO group (0.748 +/- 0.016), TTC reduction activities remained in high levels (0.144 +/- 0.002 mg/mg protein, 0.139 +/- 0.003 mg/mg protein and 0.121 +/- 0.003 mg/mg protein in SO, IO-10 and IO-15 groups, respectively). But in IO-20 and IO-30 groups, EC levels were partly restored (0.457 +/- 0.023 and 0.534 +/- 0.027) accompanying with a significantly decreased TTC reduction activities (0.070 +/- 0.005 mg/mg protein and 0.061 +/- 0.003 mg/mg protein). No recovery in EC values (0.228 +/- 0.004) and a progressive decrease in TTC reduction activities (0.033 +/- 0.002 mg/mg protein) were shown in CO-60 group. Although not significantly different, the activities of the serum aspartate aminotransferase (AST) on the third postoperative day (POD(3)) and POD(7) and of the serum alanine aminotransferase (ALT) on POD(3) in CO-60 group remained higher than that in intermittent occlusion groups. Moreover, a 60% animal mortality rate and more severe morphological alterations were also shown in CO-60 group.
Hepatic inflow occlusion during 60 minutes for liver resection in cirrhotic rats resulted in less hepatocellular injury when occlusion was intermittent rather than continuous. Each period of 15 minutes was the safe upper limit of repeated intermittent vascular occlusion that the cirrhotic liver could tolerate without undergoing irreversible hepatocellular injury.
评估不同缺血时间对肝硬化肝脏的影响，并确定反复间歇性肝血流阻断的安全上限。
在切除非缺血叶后，通过夹闭左叶和中叶的共同蒂诱导肝硬化大鼠发生肝缺血。根据血管夹闭的持续时间和方式将肝硬化大鼠分为六组：假手术组（SO）、间歇性阻断10（IO - 10）、15（IO - 15）、20（IO - 20）和30（IO - 30）分钟并再灌注5分钟以及持续阻断60分钟（CO - 60）组。所有动物的肝血流阻断总时长均为60分钟。根据肝腺苷酸能荷（EC）评估肝脏活力。测定氯化三苯基四氮唑（TTC）还原活性以定性评估不可逆性肝细胞损伤程度。还评估了生化和形态学变化，并观察了7天的死亡率。
在总共60分钟肝血流阻断后的再灌注60分钟时，IO - 10（0.749±0.012）和IO - 15（0.699±0.002）组的EC值迅速恢复至SO组（0.748±0.016）水平，TTC还原活性维持在较高水平（SO、IO - 10和IO - 15组分别为0.144±0.002mg/mg蛋白、0.139±0.003mg/mg蛋白和0.121±0.003mg/mg蛋白）。但在IO - 20和IO - 30组中，EC水平部分恢复（0.457±0.023和0.534±0.027），同时TTC还原活性显著降低（0.070±0.005mg/mg蛋白和0.061±0.003mg/mg蛋白）。CO - 60组未显示EC值恢复（0.228±0.004），且TTC还原活性逐渐降低（0.033±0.002mg/mg蛋白）。虽然差异不显著，但CO - 60组术后第3天（POD(3)）和第7天血清天冬氨酸转氨酶（AST）以及POD(3)时血清丙氨酸转氨酶（ALT）的活性仍高于间歇性阻断组。此外，CO - 60组动物死亡率为60%，且形态学改变更严重。
肝硬化大鼠肝切除术中60分钟的肝血流阻断，间歇性阻断比持续性阻断导致的肝细胞损伤更小。每15分钟的阻断时长是肝硬化肝脏能够耐受而不发生不可逆肝细胞损伤的反复间歇性血管阻断的安全上限。
