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.     

Effects of hepatic blood inflow occlusion on liver regeneration following partial hepatectomy in an experimental model of cirrhosis

BACKGROUND: Hepatic blood inflow occlusion during hepatectomy may influence postoperative liver regeneration. The aim of this study was to investigate the influence of hepatic blood inflow occlusion on liver regeneration following partial hepatectomy in thioacetamide-induced cirrhotic rats. METHODS: Forty-three cirrhotic Wistar-Furth rats were randomly assigned to three groups. Rats in group 1 underwent 64 per cent hepatectomy alone, those in group 2 were subjected to 15 min hepatic blood inflow occlusion followed by 64 per cent hepatectomy, and animals in group 3 were subjected to 30 min inflow occlusion followed by 64 per cent hepatectomy. Liver function, 5-bromo-2'-deoxyuridine (BrdU) labelling index and percentage of initial liver weight on days 1, 2 and 7 posthepatectomy were assessed. RESULTS: Rats in groups 1 and 2 had a significantly higher serum albumin level and a markedly lower alanine aminotransferase level than animals in group 3 on day 1 posthepatectomy (P < 0.05). There was no significant difference in the serum level of total bilirubin of the three groups on days 1, 2 and 7. The BrdU labelling index was significantly higher in groups 1 and 2 than in group 3 animals on day 1 posthepatectomy (P < 0.01 and P < 0.05 respectively). Percentages of initial liver weight were similar in groups 1, 2 and 3 on days 1, 2 and 7 after hepatectomy. CONCLUSION: Hepatic blood inflow occlusion for up to 30 min suppressed DNA synthesis and hepatocyte proliferation at an early posthepatectomy stage and consequently delayed recovery of liver function in cirrhotic rats. However, it did not affect restoration of liver mass or survival after 64 per cent hepatectomy.     

腹主动脉阻断导致内脏缺血再灌注损伤的研究

目的观察腹主动脉阻断所引起的肝、肾、小肠等内脏缺血再灌注损伤的改变。方法建立小猪腹主动脉阻断１小时的模型,检测在不同再灌注时点组织及血液中丙二醛（ＭＤＡ）和超氧化物歧化酶（ＳＯＤ）的变化,同时检测肝肾功能和动脉血气分析,观察动物术后的生存情况。结果与缺血前比较,大多数再灌注时点血、组织中ＭＤＡ明显升高,而ＳＯＤ明显降低（Ｐ＜０．０５）。在再灌注２小时,血中谷丙转氨酶（ＡＬＴ）、尿素氮（ＢＵＮ）、肌酐（ＣＲＥ）较缺血前明显升高（Ｐ＜０．０１）,代谢性酸中毒也极为明显。多数动物术后能够存活,但均出现下肢截瘫。结论腹主动脉阻断１小时能引起明显的内脏缺血再灌注损伤改变,多数内脏经处理后其损伤能够得到代偿恢复,而脊髓损伤恢复困难。     

Perioperative real-time monitoring of indocyanine green clearance by pulse spectrophotometry predicts remnant liver functional reserve in resection of hepatocellular carcinoma

BACKGROUND: There is no standard method for predicting remnant liver functional reserve after hepatectomy or for monitoring it in real time. METHODS: Indocyanine green (ICG) clearance (K) was measured non-invasively and instantaneously using pulse spectrophotometry before surgery, during inflow occlusion and after hepatectomy in 75 patients who underwent anatomical liver resection for hepatocellular carcinoma (HCC). RESULTS: Eight patients (11 per cent) suffered liver failure and one (1 per cent) died in hospital. An estimated remnant K value of 0.090 per min was the cut-off value for liver failure. In a logistic regression model, the estimated remnant K (0.090 per min; P = 0.022) and age (65 years; P = 0.025) were significant predictors of postoperative liver failure. There was a correlation between the estimated and measured post-hepatectomy K, and between the inflow occlusion K and measured post-hepatectomy K (P < 0.001). The cut-off value of less than 0.090 per min for the estimated remnant K resulted in 88 per cent sensitivity and 82 per cent specificity for predicting liver failure. CONCLUSION: Perioperative real-time monitoring of ICG-K is useful for evaluating the remnant liver functional reserve before, during and after liver resection for HCC. The estimated remnant K is a significant predictor of liver failure.     

Optimal cycle of intermittent portal triad clamping during liver resection in the murine liver.

We designed this experimental study to determine the optimal cycle for intermittent inflow occlusion during liver resection. A cycle of intermittent clamping (IC) for 15 minutes of ischemia followed by reperfusion for 5 minutes during liver resection is currently the most popular protocol used by experienced liver centers. As each period of reperfusion is associated with bleeding, longer periods of clamping would be advantageous. However, the longest safe duration of successive ischemia is unknown. Three groups of mice were subjected to a total liver ischemic period for 90 minutes; 2 groups underwent IC for 15 or 30 minutes, respectively, followed by 5 minutes of reperfusion, while the control group was subjected to continuous inflow occlusion only. The degree of tissue injury was assessed using biochemical and histological markers, as well as animal survival. While serious injury was observed in the continuous clamping group, both IC groups were associated with minimal injury, including lesser degrees of apoptosis and necrosis. All animals survived in the IC groups, while all animals died following 90 minutes of continuous inflow occlusion. In conclusion, intermittent portal pedicle clamping with 15- or 30-minute cycles is highly protective. A period of 30 minutes clamping should be preferred, since this would decrease the amount of blood loss associated with each cycle. This data should be confirmed in humans, and may represent a change in the current practice of hepatic surgery.     

人体常温下阻断和恢复入肝血流后肝组织病理与超微结构的临床研究

采用常温下阻断入肝血流后行肝切除手术２０例，并同时于不同时间及恢复血流后切取肝脏微型标本行光镜及电镜检查。结果显示：一次性阻断肝门３０分钟以内者，其肝脏病理及超微结构的损伤性变化是可复性的，即使肝硬变者阻断４０分钟以内术后恢复仍顺利     

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.     

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。     

Tolerance of the liver to ischemia in the pig

The effect of liver blood flow occlusion was studied in pigs under general anesthesia at normal body temperature. Portal venous blood flow was diverted to the systemic circulation during the period of liver ischemia. A 90% reduction in liver blood flow was produced during the period of ischemia as measured by ¹²⁷Xe washout. Animals subjected to 90 min of liver ischemia had uniform survival and only moderate disturbance in liver function tests. Extension of the ischemic period to 180 min produced greater disturbances in liver function tests, more hepatocellular injury histologically, and two deaths occurred. It is concluded that the pig liver can tolerate profound reductions in blood flow for extended periods of time without developing massive liver necrosis. The clinical relevance of the findings is discussed.     

A novel inhibitor of Rho-associated protein kinase,Y-27632, ameliorates hepatic ischemia and reperfusion injury in rats

BACKGROUND: A Rho-ROCK signal system induces vascular contraction and neutrophil migration, both of which are characteristic features found with ischemia and reperfusion injury of the liver. We tested our hypothesis that a novel ROCK I inhibitor, Y-27632, attenuates hepatic ischemia and reperfusion injury. METHODS: Rats underwent 70% partial hepatic ischemia for 120 minutes and subsequent reperfusion. Y-27632 of 10mg/kg was given orally 1 hour before ischemia, while distilled water was given to the control animals. One week animal survival, systemic hemodynamics, hepatic tissue blood flow, liver function tests, plasma endothelin-1, serum hyaluronic acid levels, myeloperoxidase activity and malondialdehyde level in liver tissue, membrane attack complex-1 and intracellular adhesion molecule-1 staining, and histological architecture were analyzed. RESULTS: Y-27632 prolonged 1-week animal survival from 25% of untreated animals to 75% accompanied with significant amelioration of hepatic tissue blood flow, liver function tests and histological architecture without any adverse effects on systemic hemodynamics. In addition, plasma endothelin-1 and serum hyaluronic acid levels decreased markedly compared to the control, concomitant with remarkable suppression of membrane attack complex-1 stain positive neutrophils infiltration, myeloperoxidase activity and malondialdehyde level. CONCLUSION: Present study suggests that activation of a Rho-ROCK signal system is associated with ischemia and reperfusion injury of the liver, and that Y-27632 may be an attractive agent for application in major liver resection using temporary inflow occlusion and hepatic preservation.     

The effect of hepatic ischaemia on liver function and the restoration of liver mass after 70 per cent partial hepatectomy in the dog.

Partial hepatectomy was performed in dogs either as the only procedure or following a period of ischaemia of liver remnant produced by inflow occlusion for periods of 30-60 minutes before partial hepatectomy. Temporary portal decompression was maintained through the portion of liver subsequently excised. 1. Survival in dogs subjected to partial hepatectomy and ischaemia to the liver remnant was similar to that in animals after partial hepatectomy alone. 2. Metabolic changes were similar in both groups but dogs submitted to partial hepatectomy and ischaemia to the remnant had higher serum alkaline phosphatase and alanine amino-transferase levels with increased bromsulphthalein in the fourth to sixth post-operative weeks. 3. Replacement of liver mass proceeded rapidly in all groups of animals. It is concluded that ischaemia of the liver remnant for up to 60 minutes preceding partial hepatectomy in the dog is consistent with survival and produced little change in postoperative liver function or in the rate of restoration of liver mass.     

The effect of hypothermia on liver adenosine triphosphate (ATP) recovery following combined shock and ischemia.

During both hemorrhagic shock and ischemia, adenosine triphosphate (ATP) concentrations fall in liver tissue. Incomplete recovery of ATP correlates with cell death and subsequent organ dysfunction. Changes in liver ATP levels were evaluated in paired groups of rats subjected to combined hemorrhagic shock and ischemia. A second set of paired animals was studied over time with shock alone. One animal in each pair was maintained at 28 degrees C and the other at 37 degrees C. Ischemia was produced by occluding inflow to the left half of the liver, and tissue was obtained from this area in all animals studied. Adenosine triphosphate levels fell in warm and cold animals subjected to both shock and 60 minutes of ischemia but recovered more completely during reperfusion in the cold animals. Shock alone caused a steady fall in ATP levels in the warm, but not the cold rats. These biochemical changes may indicate a beneficial effect of moderate hypothermia in the management of severe liver hemorrhage requiring temporary occlusion of blood flow.     

Efficacy of PGI2 analog in preventing ischemia reperfusion damage of liver grafts from living donors

In living-related transplantation, warm ischemia/reperfusion damage (IRD) of liver grafts is inevitable during harvesting. In this study, we investigated the effects of prostacyclin (PGI₂) on IRD of liver grafts in the rat liver transplant model. Donor rats underwent 30-min warm ischemia of part of the liver (right lateral and medial lobes). After 10 min of reflow, the ischemic partial livers were flushed with Ringer's lactate and immediately transplanted into untreated recipients. Donor animals were divided into two groups: group I received vehicle, and group II received PGI₂ analog OP-41483 (OP, 500 ng/kg per min, i. v.) during the donor operation. One-week survival was studied and cellular adenine nucleotide levels of donor livers were assayed by high-performance liquid chromatography (HPLC). Donor treatment with PGI₂ analog group II significantly improved 1-week survival (86%), in comparison with the controls group I (25%). The levels of total adenine nucleotides (TAN, μmol/g dry wt) of the grafts just before implailtation were well maintained by PGI2 treatment (12.22), as compared with the controls (10.36). In summary, PGI2 treatment of the donor maintained high energy metabolism of the liver graft after IRD and improved the survival of recipients after transplantation. Our study suggested that PGI₂ treatment of donors improves viability in liver grafts from living donors thus and increases graft availability for transplantation.     

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.     

Continuous infusion of N-acetylcysteine reduces liver warm ischaemia-reperfusion injury

BACKGROUND: N-acetylcysteine (NAC) may modulate the initial phase (less than 2 h) of liver warm ischaemia-reperfusion (IR) injury but its effect on the late phase remains unclear. The present study investigated the role of NAC during the early and late phases in a rabbit lobar IR model. METHODS: Liver ischaemia was induced by inflow occlusion to the median and left liver lobes for 60 min, followed by 7 h of reperfusion. In the NAC group (n = 6), NAC was administered intravenously at 150 mg per kg over the 15 min before reperfusion and maintained at 10 mg per kg per h during reperfusion. In the IR group (n = 6), 20 ml 5 per cent dextrose was infused over the 15 min before reperfusion and continued at a rate of 10 ml/h. Animals in a sham operation group (n = 6) underwent laparotomy but no liver ischaemia. All animals were killed at the end of the experiment. RESULTS: Intracellular tissue oxygenation was improved after the second hour of reperfusion in animals treated with NAC compared with that in the IR group (P = 0.023). Hepatic microcirculation improved after 5 h of reperfusion (P = 0.036) and liver injury was reduced after 5 h, as indicated by alanine aminotransferase activity (P = 0.007) and indocyanine green clearance (uptake, P = 0.001; excretion, P = 0.032). CONCLUSION: The main protective effect of NAC becomes apparent 5 h after hepatic ischaemic injury.     

Reduction of hepatic ischemia/reperfusion injury by a soluble P-selectin glycoprotein ligand-1.

OBJECTIVE: The authors' goal was to determine the effects of specific binding and blockade of P- and E-selectins by a soluble P-selectin glycoprotein ligand-1 (PSGL-1) in rat models of hepatic in vivo warm ischemia and ex vivo cold ischemia. The authors also sought to determine the effect of selectin blockade on isograft survival in a syngeneic rat orthotopic liver transplant model. SUMMARY BACKGROUND DATA: Ischemia/reperfusion (I/R) injury is a major factor in poor graft function after liver transplantation, which may profoundly influence early graft function and late changes. It is hypothesized that I/R injury leads to the upregulation of P-selectin, which is then rapidly translocated to endothelial cell surfaces within 5 minutes of reperfusion of the liver, initiating steps leading to tethering of polymorphonuclear neutrophil leukocytes to the vascular intima. Local production by leukocytes of interleukin-1, tumor necrosis factor-alpha, or both induces P-selectin expression on the endothelium and continues the cascade of events, which increases cell adherence and infiltration of the organ. METHODS: To examine directly the effects of selectins in a warm hepatic I/R injury model, 100 microg of PSGL-1 or saline was given through the portal vein at the time of total hepatic inflow occlusion. The effects of PSGL-1 in cold ischemia were assessed using an isolated perfused rat liver after 6 hours of 4 degrees C storage in University of Wisconsin (UW) solution, with or without the instillation of PSGL-1 before the storage. To evaluate the effect of selectin blockade on liver transplant survival, syngeneic orthotopic liver transplants were performed between inbred male Sprague-Dawley rats after 24 hours of cold ischemic storage in UW solution. A separate group of animals received two doses of 100 microg of PSGL-1 through the portal vein before storage and before reperfusion of the transplanted liver. Recipient survival was assessed at 7 days, and the Kaplan-Meier product limit estimate method was used for univariate calculations of time-dependent recipient survival events. RESULTS: In an in vivo warm rat liver ischemia model, perfusion with PSGL-1 afforded considerable protection from I/R injury, as demonstrated by decreased transaminase release, reduced histologic hepatocyte damage, and suppressed neutrophil infiltration, versus controls (p < 0.05). When cold stored livers were reperfused, PSGL-1 reduced the degree of hepatocyte transaminase release, reduced neutrophil infiltration, and decreased histologic hepatocyte damage (p < 0.05 vs. UW-only controls). On reperfusion, livers treated with PSGL-1 demonstrated increased portal vein blood flow and bile production (p < 0.05 vs. UW-only controls). In addition, 90% of the rats receiving liver isografts stored in UW solution supplemented with PSGL-1 survived 7 days versus 50% of those whose transplanted syngeneic livers had been stored in UW alone (p < 0.05). CONCLUSIONS: Selectins play an important role in I/R injury of the liver. Early modulation of the interaction between P-selectin and its ligand decreases hepatocyte injury, neutrophil adhesion, and subsequent migration in both warm and cold rat liver ischemia models. In addition, the use of PSGL-1 before ischemic storage and before transplantation prevents hepatic injury, as documented by a significant increase in liver isograft survival. These findings have important clinical ramifications: early inhibition of alloantigen-independent mechanisms during the I/R damage may influence both short- and long-term survival of liver allografts.     

Simultaneous resection of colorectal primary tumour and synchronous liver metastases

BACKGROUND: The surgical strategy for treatment of synchronous colorectal liver metastases remains controversial. The outcome and overall survival of patients presenting with such metastases, treated either by simultaneous resection or by delayed resection, were evaluated. METHODS: From 1987 to 2000, 97 patients presented with synchronous colorectal liver metastases, of whom 35 (36 per cent) underwent a simultaneous resection and 62 patients (64 per cent) a delayed resection. Simultaneous resection was considered prospectively for patients with fewer than four unilobar metastases. RESULTS: Age, blood transfusion requirements, operating time, duration of inflow occlusion, hospital stay and mortality rate were similar in the two groups. The morbidity rate did not differ significantly (23 per cent after simultaneous resection and 32 per cent after delayed resection). The location of the primary tumour and extent of liver resection did not influence the morbidity rate significantly in the simultaneous resection group. The overall survival rate was 94, 45 and 21 per cent at 1, 3 and 5 years respectively after simultaneous resection, and 92, 45 and 22 per cent after delayed resection. CONCLUSION: In selected patients, simultaneous resection of the colorectal primary tumour and liver metastases does not increase mortality or morbidity rates compared with delayed resection, even if a left colectomy and/or a major hepatectomy are required.     

The effect of nifedipine, a calcium channel blocker, on liver ischemia in dogs

This study was undertaken in order to determine whether the administration of nifedipine, a calcium channel blocker, could protect the liver from ischemic damage and to investigate its effect on the hepatic cellular energy status and cardio-vascular system after 60 minutes of hepatic ischemia in dogs. The ischemia was induced by temporarily clamping the portal vein and hepatic artery. One group of animals (n = 17) received nifedipine (5 micrograms/kg body weight) intravenously 15 minutes before the induction of liver ischemia, which was continued at a dose of 0.2 microgram/kg body weight/min throughout the ischemic period, and for an additional 30 minutes afterwards. Control dogs (n = 16) were not given nifedipine and survival was observed over seven days. The survival rate was 83 per cent in the nifedipine treated animals and 0 per cent in the control animals. Serum glutamic oxaloacetic transaminase levels were greatly increased following ischemia, and they were significantly lowered with the nifedipine treatment. The hepatic energy charge decreased remarkably during the hepatic ischemia, however it increased gradually after declamping but did not returned to its preoperative value in either group until one hour later and then it was higher in the nifedipine treated animals than in the control animals. Cardiac index and portal venous blood flow ratio remained higher in the nifedipine treated animals than in the control animals, after the ischemic period. These results suggest that nifedipine may have a powerful cytoprotective effect and that the period of warm hepatic ischemia could be prolonged with its use.     

The effect of nifedipine,a calcium channel blocker,on liver ischemia in dogs

This study was undertaken in order to determine whether the administration of nifedipine, a calcium channel blocker, could protect the liver from ischemic damage and to investigate its effect on the hepatic cellular energy status and cardio-vascular system after 60 minutes of hepatic ischemia in dogs. The ischemia was induced by temporarily clamping the portal vein and hepatic artery. One group of animals (n=17) received nifedipine (5 μg/kg body weight) intravenously 15 minutes before the induction of liver ischemia, which was continued at a dose of 0.2 μg/kg body weight/min throughout the ischemic period, and for an additional 30 minutes afterwards. Control dogs (n=16) were not given nifedipine and survival was observed over seven days. The survival rate was 83 per cent in the nifedipine treated animals and 0 per cent in the control animals. Serum glutamic oxaloacetic transaminase levels were greatly increased following ischemia, and they were significantly lowered with the nifedipine treatment. The hepatic energy charge decreased remarkably during the hepatic ischemia, however it increased gradually after declamping but did not returned to its preoperative value in either group until one hour later and then it was higher in the nifedipine treated animals than in the control animals. Cardiac index and portal venous blood flow ratio remained higher in the nifedipine treated animals than in the control animals, after the ischemic period. These results suggest that nifedipine may have a powerful cytoprotective effect and that the period of warm hepatic ischemia could be prolonged with its use.