Protective effects of ischemic preconditioning for liver resection performed under inflow occlusion in humans
Protective effects of ischemic preconditioning for liver resection performed under inflow occlusion in humans
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DOI：
10.1097/00000658-200008000-00001
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发表时间：
2000-08-01
影响因子：
9
通讯作者：
Bentley, RC
中科院分区：
文献类型：
--
作者：
Clavien, PA;Yadav, S;Bentley, RC
目的确定缺血预处理是否可以保护接受半肝切除术患者的肝脏免受随后的缺血期的影响，并确定缺血预处理可能的潜在保护机制，例如抑制肝细胞凋亡。 背景数据摘要缺血预处理是短暂的缺血期，然后在持续的缺血性损伤之前进行短暂的再灌注期。最近对啮齿动物的研究表明，缺血预处理是一种简单而有效的针对肝脏缺血性损伤的保护方式。其潜在机制被认为与细胞凋亡通路的下调有关。方法24例因各种原因接受半肝切除术的患者交替接受缺血预处理（缺血10分钟，再灌注10分钟），然后在流入阻断下进行肝脏横断恰好30分钟。在开腹时和肝切除结束后 30 分钟获取肝楔和 Tru-cut 活检样本。每天测定天冬氨酸转移酶、丙氨酸转移酶、胆红素和凝血酶原时间的血清水平直至出院。通过原位末端脱氧核苷酸转移酶介导的 d-UTP 缺口末端标记 (TUNEL) 测定和电子显微镜评估肝细胞凋亡。使用特定的荧光测定法测量组织中的 Caspase 3 和 8 活性。结果与对照组相比，接受缺血预处理的患者的血清天冬氨酸转移酶和丙氨酸转移酶水平降低了两倍以上。对轻度至中度脂肪变性患者亚组的分析表明，缺血预处理可能增强保护作用。原位TUNEL染色显示缺血预处理组中凋亡的窦状内衬细胞数量显着减少。电子显微镜证实了对照中存在细胞凋亡的特征，但缺血预处理患者中没有。缺血预处理患者与对照组相比，Caspase 3 和 8 活性没有显着差异。结论缺血预处理是一种简单有效的方法，可以保护肝脏免受随后长时间的缺血。这种策略可能是比间歇性流入阻塞更有吸引力的技术，间歇性流入阻塞与每个再灌注期间失血量增加有关。
ObjectiveTo determine whether ischemic preconditioning protects the human liver against a subsequent period of ischemia in patients undergoing hemihepatectomy, and to identify possible underlying protective mechanisms of ischemic preconditioning, such as inhibition of hepatocellular apoptosis.Summary Background DataIschemic preconditioning is a short period of ischemia followed by a brief period of reperfusion before a sustained ischemic insult. Recent studies in rodents suggest that ischemic preconditioning is a simple and powerful protective modality against ischemic injury of the liver. The underlying mechanisms are thought to be related to downregulation of the apoptotic pathway.MethodsTwenty-four patients undergoing hemihepatectomy for various reasons alternatively received ischemic preconditioning (10 minutes of ischemia and 10 minutes of reperfusion) before transection of the liver performed under inflow occlusion for exactly 30 minutes. Liver wedge and Tru-cut biopsy samples were obtained at the opening of the abdomen and 30 minutes after the end of the hepatectomy. Serum levels of aspartate transferase, alanine transferase, bilirubin and prothrombin time were determined daily until discharge. Hepatocellular apoptosis was evaluated by in situ terminal deoxynucleotidyl transferase mediated d-UTP nick end-labeling (TUNEL) assay and electron microscopy. Caspase 3 and 8 activities were measured in tissue using specific fluorometric assays.ResultsSerum levels of aspartate transferase and alanine transferase were reduced by more than twofold in patients subjected to ischemic preconditioning versus controls. The analysis of a subgroup of patients with mild to moderate steatosis indicated possible increased protective effects of ischemic preconditioning. In situ TUNEL staining demonstrated a dramatic reduction in the number of apoptotic sinusoidal lining cells in the ischemic preconditioning group. Electron microscopy confirmed features of apoptosis present in control but not in ischemic preconditioning patients. There was no significant difference in caspase 3 and 8 activity when patients with ischemic preconditioning were compared with controls.ConclusionsIschemic preconditioning is a simple and effective modality protecting the liver against subsequent prolonged periods of ischemia. This strategy may be a more attractive technique than intermittent inflow occlusion, which is associated with increased blood loss during each period of reperfusion.