Comparison of ischemic preconditioning and intermittent and continuous inflow occlusion in the murine liver

OBJECTIVE: To compare protection of the liver by ischemic preconditioning and intermittent inflow occlusion in a mouse model of prolonged periods of ischemia. SUMMARY BACKGROUND DATA: Preconditioning (short ischemic stress prior to a prolonged period of ischemia) and intermittent inflow occlusion protect the liver against reperfusion injury. This is the first study comparing these two modalities with continuous inflow occlusion (control). METHODS: Mice were subjected to 75 or 120 minutes of 70% hepatic ischemia and 3 hours of reperfusion. Each ischemic period was evaluated using three different protocols: continuous ischemia (control), preconditioning (10 minutes ischemia and 15 minutes reperfusion) prior to the prolonged ischemic insult, and intermittent clamping (cycles of 15 minutes ischemia and 5 minutes reperfusion). Organ injury was evaluated using serum levels of aspartate aminotransferase (AST), hematoxylin and eosin staining, and specific markers of apoptosis (cytochrome C release, caspase 3 activity, and TUNEL staining). Animal survival was determined using a model of total hepatic ischemia. RESULTS: Intermittent inflow occlusion and ischemic preconditioning were both protective against ischemic insults of 75 and 120 minutes compared with controls (continuous ischemia only). Protection against 75 minutes of ischemia was comparable in the intermittent clamping and the ischemic preconditioning group, whereas intermittent clamping was superior at 120 minutes of ischemia. One hundred percent animal survival was observed after 75 minutes of total hepatic ischemia using both protective protocols, whereas all animals subjected to continuous ischemia died after surgery. After 120 minutes of ischemia, intermittent inflow occlusion was associated with better animal survival (71%) compared with preconditioning (14%). CONCLUSIONS: Preconditioning and intermittent clamping are both protective against prolonged periods of ischemia. In the clinical setting, preconditioning is superior for ischemic periods of up to 75 minutes because it is not associated with blood loss during transection of the liver. However, for prolonged ischemic insults exceeding 75 minutes, intermittent clamping is superior to preconditioning.     

Prolonged continuous or intermittent vascular inflow occlusion during hemihepatectomy in pigs

OBJECTIVE: To assess ischemia and reperfusion (I/R) injury in a hemihepatectomy model in pigs after prolonged continuous or intermittent vascular inflow occlusion in the liver. SUMMARY BACKGROUND DATA: Massive intraoperative blood loss during liver resections can be prevented by temporary vascular inflow occlusion, consequently leading to ischemia and reperfusion injury in the remnant liver. Previously, in a pig liver resection model in which only limited I/R injury was induced during brief (90 min) vascular inflow occlusion, the authors demonstrated reduced I/R injury after continuous (CNT) occlusion, compared to intermittent (INT). This liver resection study on pigs was undertaken to assess I/R injury after prolonged (120 min) CNT or INT occlusion. METHODS: In pigs (37.0 +/- 1.5 kg), liver ischemia during 2 hours was CNT (n = 6) or INT (n = 6) (eight subsequent periods of 12 min ischemia and 3 min recirculation), followed by 6 hours of reperfusion. A left hemihepatectomy (45.5% +/- 1.4%) was performed within the first 12 minutes of ischemia. No hepatic pedicle clamping or liver resection was performed in control experiments (n = 6). Microvascular damage was assessed by hyaluronic acid (HA) uptake capacity of the liver (parameter of early sinusoidal endothelial cell damage) and restoration of intrahepatic tissue pO2 during reperfusion. Hepatocellular damage was tested by plasma concentrations of aspartate aminotransferase (AST), alanine aminotransferase, and lactate dehydrogenase (LDH). RESULTS: Hyaluronic acid uptake after 6 hours of reperfusion, compared to preischemic uptake, was unaltered in the control group, but was significantly reduced in both resection groups. However, more HA was taken up after INT occlusion, compared to CNT (60.4% +/- 5.6% and 39.5% +/- 3.7%, respectively; ANOVA: p = 0.001). Intrahepatic tissue pO2 distribution after 6 hours of reperfusion more closely returned to preischemic configuration in the INT group than in the CNT group, indicating reduced microcirculatory disturbances after INT occlusion. Release of AST and LDH after 6 hours of reperfusion was significantly increased in both CNT and INT groups. Lower AST levels, however, were found after INT occlusion than after CNT occlusion (267.0 +/- 74.7 U/l and 603.3 +/- 132.4 U/l, respectively; p = 0.06). CONCLUSIONS: Intermittent hepatic vascular inflow occlusion during prolonged liver ischemia in pigs resulted in less microcirculatory and hepatocellular injury, compared to continuous occlusion. Intermittent clamping is preferable when prolonged periods of vascular inflow occlusion are applied during liver resections.     

A prospective, randomized, controlled trial comparing intermittent portal triad clamping versus ischemic preconditioning with continuous clamping for major liver resection

OBJECTIVE: To evaluate whether ischemic preconditioning (IP) with continuous clamping or intermittent clamping (IC) of the portal triad confers better protection during liver surgery. SUMMARY BACKGROUND DATA: IP and IC are distinct protective approaches against ischemic injury. Since both strategies proved to be superior in randomized controlled trials (RCTs) to continuous inflow occlusion alone, we designed a RCT to compare IP and IC in patients undergoing major liver resection. METHODS: Noncirrhotic patients undergoing major liver resection were randomized to receive IP with inflow occlusion (n = 36) or IC (n = 37). Primary endpoints were postoperative liver injury and intraoperative blood loss. Postoperative liver injury was assessed by peak values of AST (alanine aminotransferase) and ALT (aspartate aminotransferase), as well as the area under the curve (AUC) of the postoperative transaminase course. Secondary endpoints included resection time, the need of blood transfusion, ICU, and hospital stay as well as postoperative complications and mortality. RESULTS: Both groups were comparable regarding demographics, ASA score, type of hepatectomy, duration of inflow occlusion (range, 30-75 minutes), and resection surface. The transection-related blood loss was 146 versus 250 mL (P = 0.008), and when standardized to the resection surface 1.2 versus 1.8 mL/cm (P = 0.01) for IP and IC, respectively. Although peak AST, AUCAST, and AUCALT were lower for IC, the differences did not reach statistical significance. Overall (42% vs. 38%) and major (33 vs. 27%) postoperative complications as well as median ICU (1 vs. 1 day) and hospital stay (10 vs. 11 days) were similar between both groups. CONCLUSIONS: Both IP and IC appear to be equally effective in protecting against postoperative liver injury in noncirrhotic patients undergoing major liver resection. However, IP is associated with lower blood loss and shorter transection time. Therefore, both strategies can be recommended for noncirrhotic patients undergoing liver resection.     

两种入肝血流阻断方式对硬化肝脏再灌注损伤的比较研究

目的:比较保留肝动脉持续门静脉阻断方式与间断肝门阻断方式对硬化肝脏的再灌注损伤。方法:四氯化碳诱导肝硬化大鼠随机分为3组:假手术对照组(SO);保留肝动脉持续门静脉阻断组(PVC);间断肝门阻断组(IC)。分别检测肝脏血流阻断45 min后复流1、6、24 h血清AST含量,行肝血流复流后吲哚青绿15 min滞留试验(ICGR15)及行组织形态学、超微结构观察。结果:肝血流复流1、6、24 h PVC组和IC组血清AST分别为607±322、791±119、375±136 IU/L和547±273、864±241、449±131IU/L,均高于SO组的188±52IU/L,3组比较差异有统计学意义(F=6.81,44.03,11.38;P<0.05),PVC组和IC组差异无统计学意义。肝血流复流1、6、24 h,PVC组及IC组ICGR15分别为(23±9)%、(19±6)%、(18±3)%和(54±9)%、(38±6)%、(29±3)%,均高于SO组的(16±4)%、(14±3)%、(15±3)%,3组比较差异有统计学意义(F=57.84,42.41,37.15;P<0.05),其中IC组最高。病理组织学检查示PVC组及IC组肝血流复流后肝组织发生点状及小片状坏死,两组间病变程度相似;超微结构显示IC组较PVC组线粒体数目增多、肿胀,部分线粒体破裂溶解。结论:与间断肝门阻断方式相比,保留肝动脉持续门静脉阻断方式对硬化肝脏功能影响更小,具有较好的临床应用前景。     

Role of ischemic preconditioning in hepatic ischemia-reperfusion injury

Background

Investigation into less traumatic method of vascular occlusion during liver resection is the actual problem in hepatic surgery because of high level of complications such as liver failure. In this connection, the goal of our study was to determine the optimal model of vascular clamping. The research showed that vascular occlusion with ischemic preconditioning in the mode 5/10/15 the most delicate technique.

Methods

Forty white giant rabbits were divided randomly into four groups (n=10 in each group). In group I we used continuous Pringle maneuver by 30 min. In group II we used intermittent Pringle maneuver: 15 min of clamping/5 min of unclamping (reperfusion)/15 min of clamping. In group III we used intermittent Pringle maneuver with ischemic precondition: 5 min of ischemia/5 min of reperfusion, 10 min of ischemia/5 min of reperfusion/15 min of ischemia. Group IV (control group) is without hepatic ischemia. All animals were performed a liver biopsy at the end of the surgery. Five rabbits from each group underwent re-laparotomy on day 3 after surgery with biopsy samples being taken for studying reparative processes in liver parenchyma.

Results

Results of morphometric analysis were the best to illustrate different level of liver injury in the groups. Thus, there were 95.5% damaged hepatocytes after vascular occlusion in hepatic preparations in group I, 70.3% damaged hepatocytes in group II, and 42.3% damaged hepatocytes in group III. There were 5.3% damaged hepatocytes in the control group.

Conclusions

Vascular occlusion with ischemic preconditioning in the mode 5/10/15 the most delicate technique that does not involve major structural injuries and functional disorders in the remnant liver. Thus, it is amenable to translation into clinical practice and may improve outcomes in liver resection with inflow vascular occlusion.     

Ischemic preconditioning impairs liver regeneration in extended reduced-size livers

OBJECTIVE: To evaluate the effect of ischemic preconditioning (IPC) in an experimental setting of extended liver resection with 30 minutes of inflow occlusion in rats. SUMMARY BACKGROUND DATA: IPC has been proven an effective strategy against hepatic ischemia-reperfusion injury in both animal and human studies. However, decreased protective effects in terms of transaminase levels were found in patients with larger resection volume, questioning the benefit of IPC in case of small liver remnants. METHODS: Rats undergoing 90% hepatectomy under strict inflow occlusion for 30 minutes were subjected to either receive or not receive an IPC period (5 minutes of ischemia followed by 30 minutes of reperfusion). In addition to 10-day survival rate, laser Doppler flowmetry of hepatic blood flow and fluorescence microscopic analysis of the hepatic microcirculation were performed to assess the effect of IPC on initial microvascular reperfusion of liver remnants after 90% resection. Moreover, regeneration capacity of livers undergoing IPC and 70% resection was studied over 7 days by means of histology and immunohistochemistry. RESULTS: Ten-day survival of rats which underwent IPC and 90% hepatectomy was 0 out of 10 animals versus 1 out of 10 animals without IPC. Hemodynamic and microcirculatory analysis revealed signs of hyperperfusion during initial reperfusion of preconditioned liver remnants in 90% hepatectomized animals. In addition to increased transaminase levels, IPC impaired hepatic proliferative response after 70% organ resection, as indicated by both a significant reduction in mitotic figures and Ki-67 nuclear staining of hepatocytes, as well as a decrease in restitution of liver mass. CONCLUSIONS: Though portal hypertension reflecting shear stress has been reported to trigger liver regeneration, remnant liver tissue after major hepatectomy may not benefit from hyperperfusion-induced trigger for cell cycle entry but is rather dominated from hyperperfusion-induced local organ injury. Further studies are required to finally judge on the harmfulness of IPC in extended liver resection.     

Ischemic preconditioning and intermittent clamping increase the tolerance of fatty liver to hepatic ischemia-reperfusion injury in the rat

INTRODUCTION: Liver ischemia-reperfusion (I/R) injury is a well-known cause of morbidity and mortality following liver surgery and transplantation. Hepatic steatosis increases the extent of cellular injury incurred during I/R injury. We sought to identify measures that reduced the untoward sequelae of liver I/R injury. METHODS: Male Zucker rats were subjected to 75 minutes of 70% hepatic ischemia, and 3 hours of reperfusion. The ischemic periods were based on the following protocols: continuous clamping (CC) for 75 minutes; intermittent clamping (IC) with five cycles of 15 minutes clamp on and 5 minutes clamp off; or ischemic preconditioning (IP) with 10 minutes clamp on, 15 minutes off, and 60 minutes on (n=7 in each group). Warm I/R injury was evaluated using serum levels of aspartate aminotransferase (AST), serum interleukin (IL)-6, as well as hematoxylin and eosin staining. RESULTS: Hepatocellular injury was significantly reduced with IP or IC compared with CC (AST: 3285+/-122.3 and 2875+/-285.4 compared with 5436.3+/--984.7 units/L, respectively; P<.01). Serum IL-6 level was also significantly reduced with IP and IC compared with CC (70+/-8.8 and 76+/-6.2 compared with 147+/-8.5 ng/l, respectively (p<.01). Histological analysis also revealed that IC and IP provided significant protection compared with the CC group. CONCLUSION: IC and IP increased the tolerance of a fatty liver to hepatic I/R injury.     

Continuous or intermittent vascular clamping during hemihepatectomy in pigs: hyaluronic acid kinetics in the assessment of early microvascular liver damage.

OBJECTIVE: To assess the uptake of hyaluronic acid (HA) as a marker of microvascular damage in a model of hemihepatectomy in pigs having continuous or intermittent vascular inflow occlusion. DESIGN: Prospective, animal study. SETTING: Laboratory for experimental surgery, University hospital, The Netherlands. INTERVENTIONS: Total liver ischaemia was achieved during 90 minutes by continuous (n = 5) or intermittent (n = 5) occlusion of the portal vein and hepatic artery followed by 120 minutes of reperfusion. In a second series of pigs (n = 8) a left hemihepatectomy was added to the protocol. MAIN OUTCOME MEASURES: Uptake of exogenous HA was assessed before ischaemia and after 120 minutes of reperfusion, together with the galactose elimination capacity. Plasma activities of aspartate aminotransferase (AST), alanine amino transferase, and lactate dehydrogenase were measured and specimens of liver were obtained for histopathological examination. RESULTS: HA uptake was slightly reduced after reperfusion in unresected livers compared with uptake before ischaemia. After hemihepatectomy HA uptake after reperfusion was significantly reduced after both continuous and intermittent occlusion, but more HA was taken up after continuous occlusion (p = 0.02). Release of AST after reperfusion was increased only after hemihepatectomy. CONCLUSIONS: Microvascular damage, as assessed by HA uptake capacity, significantly contributed to normothermic ischaemia and reperfusion injury in porcine liver. Vascular inflow occlusion during 90 minutes in combination with hemihepatectomy resulted in less liver damage when vascular occlusion was continuous rather than intermittent.     

Preconditioning protects against ischemia/reperfusion injury of the liver

Ischemic preconditioning (IPC) of an organ may induce protection against the injury caused by longer duration of ischemia and subsequent reperfusion. In a standardized model of such injury in the rat liver, we used the following protocol to investigate whether adenosine played a role in IPC by preventing its enzymatic degradation by dipyridamole pretreatment according to the following protocol: group 1, non-ischemic control rats; group 2, ischemic control rats subjected to 60 minutes of ischemia by clamping of the common hepatic artery followed by 60 minutes of reperfusion; group 3, IPC with 10 minutes of ischemia followed by 15 minutes of reperfusion, prior to the ischemia/reperfusion period as in group 2; group 4, pharmacologic preconditioning with administration of dipyridamole prior to the ischemia/reperfusion period as in group 2. Peripheral liver blood flow was significantly reduced during clamping (groups 2 to 4). After unclamping, blood flow was still reduced in the ischemic rats (group 2) but had returned to preclamp values in the animals that had been subjected to ischemic (group 3) or pharmacologic (group 4) preconditioning. Liver cell injury was significantly increased in the ischemia group (group 2) only. In our experimental model of ischemia/reperfusion injury in the rat liver, we found an equally beneficial effect with ischemic and pharmacologic preconditioning. Adenosine appears to be a crucial factor in IPC.     

Protective effects of ischemic preconditioning for liver resection performed under inflow occlusion in humans

OBJECTIVE: To 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 DATA: Ischemic 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. METHODS: Twenty-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. RESULTS: Serum 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. CONCLUSIONS: Ischemic 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.     

Bile duct exclusion from selective vascular inflow occlusion in rat liver: role of ischemic preconditioning and N-acetylcysteine on hepatic reperfusion injury

AIM: To study the effects of N-acetylcysteine and ischemic preconditioning on the portal triad clamping compared to arterial and portal clamping alone. METHODS: Eighty EPM 1-Wistar rats were randomized into two groups, depending on inclusion (Group 1) or not (Group 2) of the bile duct in the hepatic vascular pedicle occlusion. Each group was divided into four subgroups as follows. IR 1: 20 minutes after celiotomy, the pedicle containing vascular elements and bile duct to the left lateral and median liver lobes was occluded for 40 minutes, followed by 30 minutes of reperfusion. IPC 1: after 10 minutes of ischemia and 10 minutes of reperfusion, the ischemic preconditioning period, the rats were submitted to the same procedure described for IR 1 Group. NAC 1: the rats received N-acetylcysteine (150 mg/kg) 15 minutes before 40 minutes of ischemia and 5 minutes before 30 minutes of reperfusion. SHAM 1: The hepatic pedicle for the lateral and median liver lobes was dissected after 20 minutes, the bile duct alone was clamped for 40 minutes, and released for an additional 30 minutes. In the IR 2, IPC 2, and NAC 2 groups, ischemia was achieved with an exclusive vascular occlusion. SHAM 2: dissection and observation for 90 minutes. The blood was sampled for liver enzyme levels. Statistical analysis was done (P 相似文献   

大鼠门静脉转流下耐受入肝血流阻断的安全时限

目的 评估在排除门静脉淤血条件下动物耐受入肝血硫阻断的安全时限。方法 利用大鼠肝脏及肝蒂分支分叶的解剖特点,阻断肝左、中和右叶肝蒂,以尾叶静脉系统作为阻断入肝血流期间门静脉血液的流出道,肝脏复流后切除尾叶。在这一模型上,以阻断入肝血流不同时程后动物7d存活率、肝脏病理组织学改变及肝脏能量代谢功能损害的严重度及可逆性来推断动物耐受常温下入肝血流阻断的安全时限。结果 门静脉转流下阻断入肝血流90min以内,术后7d动物全部存活,其肝脏缺血-再灌流损害以肝窦淤血和肝细胞变性等可逆性病变为主,而肝脏能量代谢功能损害可得以代偿和恢复。阻断入肝血流100、110、120min后动物7d存活率分别为50％、30％和20％,肝脏缺血120min后肝脏缺血-再灌流损害则以大量肝组织坏死为显著特性,其肝脏能量代谢功能严重受损而陷入失代偿状态。结论 大鼠在门静脉轻流时对常温下持续入肝血流阻断的耐受性显著增强,其安全时限是90min。     

Evaluation of liver damage after application of TVE in the rat model

INTRODUCTION: The aim of this study was to investigate the effects of total vascular exclusion (TVE) on the liver during the early period of reperfusion. MATERIALS AND METHODS: Forty Wistar-Albino rats were divided into four groups. Portal pedicle clamping (groups 1 and 2) or TVE (groups 3 and 4) were applied for 10 minutes. Samples were collected at the time of clamp release (groups 1 and 3) and at 30 minutes of reperfusion (groups 2 and 4). We examined oxidative injury to and histopathology of the liver. RESULTS: Oxidative stress was more prominent with TVE application. Significant alterations were shown in hepatic superoxide dismutase, catalase, glutathione, and glutathione S-transferase levels. The levels of malondialdehyde and myeloperoxidase were not altered significantly. CONCLUSION: Inflow-outflow occlusion of the liver causes more oxidative stress compared with inflow occlusion.     

Effects of the free radical scavenger dimethyl sulphoxide on experimental normothermic ischaemia of the liver

BACKGROUND/AIMS: This study assessed the effects of intermittent or continuous hepatic ischaemia and reperfusion with or without dimethyl sulphoxide (DMSO) pre-treatment in a rat ischaemic model. METHODS: One hundred and eighty rats were divided into three groups undergoing hepatic ischaemia of a total duration of 60, 90 and 120 min. Each group of rats was subdivided to receive either a continuous Pringle manoeuvre or intermittent liver pedicle clamping of 30 or 15 min. Ten minutes before ischaemia induction, 10 rats from each group were pre-treated with DMSO (500 mg/kg, b.w.) intravenously. RESULTS: With continuous hepatic pedicle clamping, survival rates inversely correlated with the duration of ischaemia, with greater survival in the intermittently clamped groups (p < 0.05). DMSO pre-treatment did not affect survival but resulted in a significant reduction in liver enzyme (aspartate aminotransferase, alanine aminotransferase) release on the first postoperative day following total ischaemic times of 90 min or greater (p < 0.05). After 120 min of total ischaemia, DMSO pre-treatment resulted in higher preservation of adenosine 5'-triphosphate liver content (p < 0.05). CONCLUSION: DMSO may be used to prolong tolerance to inflow occlusion and to limit the adverse effects of ischaemia and reperfusion cycles in an experimental hepatic ischaemia model.     

常温下一次性和间断肝门阻断对肝损伤的对比研究及还原型谷胱甘肽的保护作用

目的 对比常温下一次性和间断人肝血流阻断法所致肝损伤,并探讨还原型谷胱甘肽的保护作用。方法 SD大鼠32只,按人肝血流阻断方式及是否应用还原型谷胱甘肽(GSH)分为4组,即一次性阻断加和不加GSH(CP和CA)组及间断阻断加和不加GSH(IP和IA)组,每组8只。CP和CA组持续阻断肝门40min,IP和IA组阻断2个20min并间隔5min,再灌注时间为60min。观察指标为肝组织丙二醛(MDA)和铜/锌超氧化物歧化酶(Cu/Zn SOD)含量,血ALT和AST活性及肝组织光镜和电镜观察。结果 组内比较,阻断后血ALT及AST活性较阻断前明显增高,差异有显著意义(P<0.05),MDA和Cu/zn SOD含量则无显著性差异(P>0.05)。再灌注后各值较阻断前均有显著性差异(P<0.05)。组间比较,CP与IP及CA与IA组间各观察值差异均无显著意义(P>0.05)。而再灌注后CP与CA组、IP和IA组比较均有显著性差异(P<0.05)。形态学上,各组阻断后均有细胞损伤表现,再灌注后有所恢复,其中CP和IP组肝细胞结构基本恢复正常,而CA和IA组仍有部分细胞呈空泡变性。各组各时点均未出现不可复性损伤。结论 常温下一次性和间断阻断肝门40min均可导致可复性肝损伤,其程度无明显差异。此时限内一次性阻断是肝切除术中适宜的阻断方法。术中应用GSH对其有明显的对抗作用,可能成为一种新的保护方法。     

To clamp or not to clamp: Inflow occlusion during liver resection

Aim: To review the evidence in using inflow occlusion during liver resection. Other strategies to minimize the untoward effects of inflow occlusion will also be discussed. Methods: Randomized trials evaluating the use of inflow occlusion in hepatectomy and strategies to minimize its associated adverse effects were reviewed in this article. Recent experience showing comparable operative outcomes without the use of portal clamping was also described. Results: Results from randomized trials and meta‐analyses were not conclusive on the benefits of routine inflow occlusion during liver resection. Intermittent inflow occlusion and ischaemic preconditioning had been found to be effective in reducing ischaemic–reperfusion injury to remnant liver. With refined operative techniques and better instruments, routine inflow occlusion in liver resection can now be safely avoided. Conclusion: Vascular inflow occlusion is an important armamentarium during liver resection, but it should not be used indiscriminately. With refined techniques and better instruments, hepatectomy can be performed safely without the need for routine inflow occlusion.     

A prospective randomized study in 100 consecutive patients undergoing major liver resection with versus without ischemic preconditioning

OBJECTIVE: To evaluate the protective effects of ischemic preconditioning in a prospective randomized study involving a large population of unselected patients and to identify factors affecting the protective effects. SUMMARY BACKGROUND DATA: Ischemic preconditioning is an effective protective strategy in several animal models. Protection has also been suggested in a small series of patients undergoing a hemihepatectomy with 30 minutes of inflow occlusion. Whether preconditioning confers protection in other types of liver resection and longer periods of ischemia is unknown. Therefore, we conducted a prospective randomized study to evaluate the impact of ischemic preconditioning in liver surgery. METHODS: A total of 100 unselected patients undergoing major liver resection (> bisegmentectomy) under inflow occlusion for at least 30 minutes were randomized during surgery to either receive or not receive an ischemic preconditioning protocol (10 minutes of ischemia followed by 10 minutes of reperfusion). Univariate and multivariate analyses were performed to identify independent factors affecting the protective effects of ischemic preconditioning. ATP contents in liver were measured as a possible mechanism of protection. RESULTS: Both groups (n = 50 in each) were comparable regarding age, gender, duration of inflow occlusion, and resected liver volumes. Postoperative serum transaminase levels were significantly lower in preconditioned than in control patients (median peak AST 364 U/L vs. 520 U/L, P = 0.028; ALT 406 vs. 519 U/L, P = 0.049). Regression multivariate analysis revealed an increased benefit of ischemic preconditioning in younger patients, in patients with longer duration of inflow occlusion (up to 60 minutes), and in cases of lower resected liver volume (<50%). Patients with steatosis were also particularly protected by ischemic preconditioning. ATP content in liver tissue was preserved by ischemic preconditioning in young but not older patients. CONCLUSIONS: This study establishes ischemic preconditioning as a protective strategy against hepatic ischemia in humans. The strategy is particularly effective in young patients requiring a prolonged period of inflow occlusion, and in the presence of steatosis, and is possibly related to preservation of ATP content in liver tissue. Other strategies are needed in older patients.     

Ischemia-reperfusion injury of the human liver during hepatic resection

Haemorrhage during resection of the liver remains a significant threat to clinical outcome. Portal triad occlusion, with complete clamping of the hepatic inflow at the hepatoduodenal ligament, is a well-documented, safe, and useful means of alleviating this problem. Although this technique is effective in limiting blood loss, there is still controversy concerning the potential drawbacks of ischemia and subsequent reperfusion injury of the liver. This article highlights recent advances in our understanding of the clinical factors influencing ischemia-reperfusion injury of the liver, particularly in human patients. These factors include the cell components involved, the mechanisms that enable the human liver to tolerate long-term inflow occlusion, factors affecting clinical outcomes, and surgical and pharmacological techniques used to alleviate ischemia-reperfusion injury, including hypothermic hepatectomy.     

Vascular occlusion techniques during liver resection

Control of bleeding from the transected liver basically consists of vascular inflow occlusion and control of hepatic venous backflow from the caval vein. Central venous pressure determines the pressure in the hepatic veins and is an extremely important factor in controlling blood loss through venous backflow. Vascular inflow occlusion (Pringle maneuver) involves clamping of the portal vein and the hepatic artery in the hepatic pedicle and gives rise to postischemic, reperfusion injury. Several strategies have been devised to reduce reperfusion injury (pharmacological interventions) or to increase ischemic tolerance of the liver (ischemic preconditioning). Intermittent clamping is recommended in complex liver resections or in patients with diseased livers. The combination of occlusion of vascular inflow and outflow of the liver results in total hepatic vascular exclusion (THVE) and is mainly used in tumors invading the caval vein. During THVE the liver can be cooled by hypothermic perfusion allowing for extended ischemia times. Selective THVE entails clamping of the main hepatic veins in their extrahepatic course, thus preserving caval flow. Safe liver surgery requires knowledge of the regular techniques of vascular occlusion for 'on demand' use when necessitated to reduce blood loss.