选择性入肝血流阻断对肝脏能量代谢的影响

目的 探讨选择性入肝血流阻断对肝脏能量代谢的影响。方法 用自行设计的可避免大鼠门静脉淤血的动物模型,通过分析阻断和恢复入肝血流后肝脏三磷酸腺苷、呼吸控制率,磷氧比值动脉血酮体比值的变化与恢复过程,并与完全入肝血流阻断组及假手术组相对照。结果 选择性入肝血流阻断对肝脏能量代谢的变化及恢复过程与完全入肝血流阻断者差异有显著意义,前者的恢复明显好于后者。结论 选择性入肝血流阻断对肝脏能量代谢的改变与恢复过程有积极的作用。     

Attenuation of endotoxin-induced increase in glucose metabolism by platelet-activating factor antagonist

Platelet-activating factor (PAF) has recently been proposed as a putative mediator of various pathophysiologic events during endotoxemia. The aim of the present study was to determine the relative importance of PAF in producing the alterations in carbohydrate metabolism following endotoxin. Chronically catheterized conscious rats were treated with SRI 63-441, a specific PAF receptor antagonist, or saline prior to Escherichia coli endotoxin (100 micrograms/100 g body weight, LD10) administration. Hemodynamic and whole-body glucose kinetic changes, the latter assessed by a constant intravenous infusion of [6-3H] glucose, were determined throughout the 4-hr experimental protocol. Endotoxin induced a transient 30-35% reduction in mean arterial blood pressure (MABP) in animals treated with saline. The PAF-antagonist attenuated this hypotensive effect, and MABP was only reduced by 14-18%. Endotoxin increased plasma glucose and lactate levels, as well as the rate of glucose appearance (Ra) in saline-treated rats. The PAF antagonist reduced the hyperglycemia by 60-75% and tended to prevent the hyperlactacidemia. The endotoxin-induced elevation in glucose Ra was also attenuated by 55%. A similar degree of hyperglucagonemia was observed following endotoxin in both groups, and plasma insulin concentrations were not different. However, plasma catecholamine levels were significantly lower (30-70%) in endotoxemic rats treated with the PAF antagonist. These results suggest that the enhanced production of PAF following endotoxin may be responsible, at least in part, for the early hemodynamic changes. The role of PAF as a mediator of endotoxin-induced glucose dyshomeostasis, however, may be secondary to its hemodynamic effects.     

Protective effect of methylprednisolone and of intermittent hepatic pedicle clamping during liver vascular inflow occlusion in the rat

BACKGROUND/AIMS: One of the main causes of postoperative morbidity and mortality following major hepatic resection is hepatic ischemia deliberately designed to reduce intraoperative hemorrhage. This study assessed the effects of intermittent or continuous hepatic ischemia and reperfusion with or without methylprednisolone pretreatment in the rat. METHODOLOGY: One hundred and eighty rats were divided into 3 groups undergoing hepatic ischemia of 60, 90, and 120 minutes total duration. Each group of rats were subdivided to receive either a continuous Pringle maneuver, or 30 min or 15 min of intermittent liver pedicle clamping. Ten minutes before ischemia induction, 10 rats from each group were pretreated with intravenous 3 mg/100 g bw methylprednisolone. RESULTS: With continuous hepatic pedicle clamping the rat survival rates inversely correlated with the duration of ischemia (survival: 70%, 40%, and 20% with ischemia of 60, 90, and 120 min). Survival rates at 15-min and 30-min intermittent ischemia groups were significantly higher than in the continuous clamping group (p<0.05). Methylprednisolone pretreatment did not significantly increase survival but resulted as a significant reduction in liver enzyme release (AST, ALT), at 90 min (p<0.05) and at 120 min (p<0.05) in the continuously clamped groups. When ischemia lasted 120 min, methylprednisolone pretreatment was associated with higher preservation of ATP liver content (p<0.05). CONCLUSIONS: This study confirms that intermittent hepatic pedicle clamping significantly improves survival in rats undergoing hepatic vascular inflow occlusion with a decrease in transaminase release and greater maintenance of intrahepatic ATP after prolonged total ischemia when animals were pretreated with methylprednisolone.     

葛根素对再灌注损伤肝能量代谢的保护作用及机制

[目的]研究葛根素对兔缺血再灌注损伤中肝脏能量代谢的改善作用及其机制。[方法]将30只家兔随机均分为对照组(C组)、缺血/再灌注组(IR组)和葛根素组(Pur组)。测定血浆中谷丙转氨酶(ALT)浓度和肝组织内一磷酸腺苷(AMP)、二磷酸腺苷(ADP)、三磷酸腺苷(ATP)、总腺苷酸量(TAN)、肝脏的细胞能荷(EC)、丙二醛(MDA)、超氧化物歧化酶(SOD)、一氧化氮(NO)、内皮素(ET)、NO/ET、血栓素B2(TXB2)、前列腺素F1α(PGF1α)、TXB2/PGF1α水平,并观察肝细胞形态学的改变。[结果]与C组比较,IR组血浆ALT浓度、肝组织AMP、ADP、MDA、ET含量显著升高(P0.01),TXB2、TXB2/PGF1α亦明显升高(P0.05),肝组织ATP、EC、SOD、NO/ET显著下降(P0.01),NO、PGF1α亦明显降低(P0.05),TAN差异无统计学意义(P0.05),肝细胞形态学异常改变;与IR组比较,Pur组血浆ALT浓度、肝组织AMP、MDA、ET含量显著降低(P0.01),肝组织ADP、TXB2/PGF1α亦明显减少(P0.05),TXB2略低于IR组(P0.05),肝组织ATP、EC、SOD、NO/ET显著升高(P0.01),肝组织NO、PGF1α亦明显增高(P0.05),TAN差异无统计学意义(P0.05),肝细胞形态学异常改变较大程度减轻。[结论]葛根素(60mg/kg)预处理可通过拮抗氧化损伤、调节NO/ET和前列腺素I2/血栓素A2(PGI2/TXA2)失衡而改善肝细胞的能量代谢,有效防治兔肝再灌注损伤。     

间歇性全入肝血流阻断与区域性入肝血流阻断腹腔镜肝切除术治疗原发性肝癌患者术后恢复研究*

目的 探讨采取间歇性全入肝血流阻断与区域性入肝血流阻断腹腔镜肝切除术(LH)治疗原发性肝癌(PLC)患者术后恢复情况。方法 2016年3月～2021年3月我院诊治的128例PLC患者,均接受LH手术治疗,其中57例在术中采取间歇性全入肝血流阻断法,另71例采取区域性入肝血流阻断法。监测平均动脉压(MAP)和心率(HR),使用多普勒超声检测门静脉血流速度(PVV)。结果 区域血流阻断组术中出血量和肝血流阻断时间分别为(305.4±58.6)mL和(0.0±0.0)min,显著少于或短于全肝血流阻断组【分别为(382.5±60.3)mL和(24.2±7.5)min,P＜0.05】;在术后7 d,区域血流阻断组血清总胆红素水平为(16.4±8.5)μmol/L,血清白蛋白水平为(35.6±5.3)g/L,与全肝血流阻断组【分别为(25.7±7.2)μmol/L和(32.4±4.9)g/L】比,差异显著(P＜0.05);区域血流阻断组MAP、HR和PVV分别为(85.6±2.3)mmHg、(78.7±8.3)次/min和(20.3±0.2)cm/s,与全肝血流阻断组【分别为(86.8±2.5)mmHg、(79.6±8.1)次/min和(20.1±0.3)cm/s】比,差异无统计学意义(P＞0.05);术后,区域血流阻断组腹腔内出血、胆汁漏、胸腔积液和肺部感染发生率分别为1.4%、8.5%、14.1%和5.6%,与全肝血流阻断组(分别为3.5%、10.5%、22.8%和10.5%)比,差异无统计学意义(P＞0.05)。结论 采取区域性入肝血流阻断LH治疗PLC患者有较好的手术和术后恢复效果,能够有效降低术中出血量,减少肝血流阻断时间,减轻术后肝功能损伤。     

The effect of trimetazidine on liver regeneration after partial hepatectomy under hepatic blood inflow occlusion

BACKGROUND/AIMS: It has been shown that hepatic blood inflow occlusion impairs liver regeneration. Our aim in this study was to investigate the effect of trimetazidine, known as an anti-ischemic and anti-oxidant agent, on liver regeneration after hepatic blood inflow occlusion. METHODOLOGY: Sprague-Dawley rats were randomized into three groups. Rats in group 1 underwent 65% hepatectomy. Rats in group 2 and 3 were subjected to 15 minutes of hepatic blood inflow occlusion during 65% hepatectomy. Rats were treated with saline (in group 1 and 2) or trimetazidine (in group 3) 30 minutes before operation. Serum level of aspartate transaminase, wet to dry liver weight ratio, and liver injury score in light microscopy were studied for the evaluation of liver injury. Liver regeneration was evaluated by PCNA-labeling index (the percentage of hepatocytes staining for proliferating cell nuclear antigen), mitotic index (the percentage of mitotic hepatocytes), and liver regeneration rate (the percentage of initial liver weight). RESULTS: Rats in group 2 and 3 had significantly higher serum aspartate transaminase level, wet to dry liver weight ratio and injury score than those in group 1 on day 1 posthepatectomy. Except for serum aspartate transaminase level on day 4, these parameters were significantly higher in group 2 than in group 1 and 3 on day 1 and 4. PCNA-labeling index and mitotic index were significantly less in group 2 and 3 than in group 1 on day 1. In contrast to liver regeneration rate, both indices in group 2 were significantly less than those in group 3 on day 1. There were no differences in regeneration parameters between the groups on day 4. Survival rate was significantly higher in group 3 than in group 2. CONCLUSIONS: Fifteen minutes of hepatic blood inflow occlusion caused an injury in the remnant liver, impaired liver regeneration, and decreased survival rate after partial hepatectomy. However, pretreatment with trimetazidine reduced liver injury, and improved liver regeneration and survival rate. For situations where hepatic blood inflow occlusion is planned in major liver resection, trimetazidine pretreatment would be useful strategy to improve postoperative outcome.     

Strong association between frequency of intermittent inflow occlusion and transient increase in serum liver enzymes after hepatic resection

BACKGROUND/AIMS: Although significantly higher serum levels of liver transaminases are commonly observed after hepatic resection, the factors responsible for the increase and the association between the increase and the postoperative course remain unclear. METHODOLOGY: The study population comprised 70 patients who had undergone hepatic resection except hepatectomy with vascular and biliary reconstruction. The relation between the perioperative factors and postoperative aspartic aminotransferase (AST) and alanine aminotransferase (ALT) elevations were analyzed. Outcome parameters, i.e., postoperative total bilirubin level, hospital stay and complications were also analyzed. RESULTS: The average maximum postoperative serum AST and ALT levels were 444.6 IU/L and 390.1 U/L. None of the preoperative factors examined, such as AST, ALT, associated liver disease, Liver Damage Classification, intraoperative hypotension, intraoperative blood loss or types of liver resection, were significantly correlated with liver enzyme elevations. The only factor that was significantly correlated was frequency of intermittent inflow occlusion (p < 0.001). The elevations of AST and ALT were not significantly correlated with length of hospital stay and postoperative serum bilirubin level. ALT also was not correlated to complications, whereas AST was significantly correlated to the frequency of the postoperative complications. CONCLUSIONS: The frequency of intermittent inflow occlusion is the only factor that affects the postoperative enzyme elevation.     

Damage and repair of hepatocyte nuclear DNA after hepatic inflow occlusion.

Recent reports emphasize that ischemic tissue damage is caused mainly by superoxide produced at the reperfusion rather than by ischemia itself. In this paper, the damage and repair of hepatocyte nuclear DNA of is investigated using rats with portasystemic shunt. Hepatic inflow was occluded for 30, 60 and two times 30 (with a 10-minute interval) minutes. Extent of DNA damage and repair were measured by nick-translation and 3H-thymidine incorporation, respectively. Superoxide, GOT and endotoxin were also measured. The results are as follows. 1. Sixty minutes of ischemia produced more serious DNA damage of the hepatocyte nucleus and a significant delay in repair as compared with 30 minutes of ischemia. 2. Intermittent ischemia for two times 30 minutes produced milder damage to DNA, and earlier recovery than a single ischemia of 60 minutes. 3. Serum and tissue peroxide increased after reperfusion in 60 minutes and intermittent ischemia, but not after 30 minutes of ischemia. Endotoxin level increased only in 60-minute ischemia. Histological change, neutrophilic cell infiltration, was most prominent in 60-minute ischemia. On the basis of these data, insofar as the duration of ischemia is not so long that cell damage becomes irreversible, damage by superoxide after reperfusion will be negligible. Therefore, intermittent short-term inflow occlusion is preferable in hepatic surgery.     

Influence of a platelet-activating factor antagonist on severe pancreatitis in two experimental models.

This study investigates the role of platelet-activating factor (PAF) in experimental pancreatitis. The concentration of PAF quantified in ascites of bile-induced pancreatitis by radioimmunoassay (RIA) ranged from 3.67 +/- 0.39 pmol/mL 2 h to 0.954 +/- 0.39 pmol/mL 10 h after injection of taurocholate. Administration of a potent PAF antagonist, WEB-2170, prior to injection of taurocholate prolonged mean survival time in rats receiving i.v. camostate and albumin (46.4 h, n = 15, vs controls 38.3 h, n = 13). However, the survival rate after 72 h was not improved. The histologically estimated severity of pancreatitis and pancreatic enzymes in blood, tissue, or ascites was not affected. WEB-2170 had no effect on survival when injected simultaneously with taurocholate into the pancreatic duct or given i.v. after induction of pancreatitis (1, 0.1, or 0.01 mg/kg WEB-2170 vs controls). Subcutaneous injection of 10 mg/kg WEB-2170 also did not improve survival in pancreatitis induced by choline-deficient, ethionine-supplemented diet in mice. It is concluded that administration of a PAF antagonist after the onset of severe experimental pancreatitis does not influence its outcome, although activation of PAF may play a role in the pathogenesis of pancreatitis.     

Protective effect of BN 52021, a specific antagonist of platelet-activating factor (PAF-acether) against diet-induced cholesteryl ester deposition in rabbit aorta

Platelet-activating factor (PAF-acether), a phospholipid mediator involved in inflammatory reactions, has been reported to induce endovascular surface lesions. We investigated the possible involvement of PAF-acether in the mechanism of arterial cholesterol deposition. Rabbits fed a normal or hypercholesterolic diet were treated orally for 1 month with BN 52021 (20 mg/kg per day), a specific PAF-acether antagonist, and killed at the end of treatment. Cholesterol feeding resulted in a marked (50-fold) increase in plasma cholesterol. However, the drug had no significant effect on the diet-induced hypercholesterolemia. Free and esterified cholesterol were markedly increased (635%) in the aorta of animals receiving the atherogenic diet. This accumulation was reduced by 36% upon simultaneous administration of BN 52021 (P less than 0.02, n = 15). This decrease essentially affected the esterified cholesterol content. Conversely, BN 52021 showed no effect on the cellular cholesterol esterification, since liver acyl-CoA: cholesterol acyltransferase activity remained unchanged. This study indicates that BN 52021 is effective in reducing cholesterol accumulation in rabbit atherosclerotic aorta, without changing the plasma cholesterol levels.     

Effect of platelet-activating factor antagonist and leukotriene antagonist on endotoxin shock in the rat: role of the leukocyte.

The effects of platelet-activating factor (PAF) antagonist (CV-3988) and leukotrienes (LTs) antagonist (ONO-1078) on endotoxin-induced sequelae in the rat were assessed. Pretreatment with either CV-3988 (6 mg/kg, i.v.) or ONO-1078 (150 mg/kg, p.o.) did not improve survival rate following the administration of Escherichia coli lipopolysaccharide (LPS) compared with that of control rats pretreated with solvents of the drugs. Rats pretreated with both CV-3988 and ONO-1078 exhibited significantly (P less than 0.01) enhanced survival following lipopolysaccharide (LPS) administration. Percentage survivals 48 hr after the administration of LPS were 20%, 32%, 24%, and 68% in the pretreatment with solvents, CV-3988, ONO-1078, and CV-3988 combined with ONO-1078 groups, respectively. Pretreatment with CV-3988 combined with ONO-1078 inhibited the change of plasma transaminase 3 hr after LPS administration. The neutropenia, due to the administration of vinblastine (1 mg/kg, i.v.), increased the survival rate following the administration of LPS without pretreatment with PAF and LT antagonists. Antishock action of CV-3988 and ONO-1078 could not be seen in neutropenic rats. These data suggest that combined pretreatment with PAF antagonist and LT antagonist inhibited leukocyte-mediated tissue injury in LPS-induced endotoxemia.     

Leukotriene metabolism by intrapulmonary vessels of newborn lambs: effect of platelet-activating factor

Leukotrienes (LTs) are potent vasoconstrictors in the pulmonary circulation. We investigated LTB4 and LTE4 metabolism by intrapulmonary arteries and veins of 2 to 9 days old lambs (n = 6). Paired vessels were incubated under baseline, and stimulated conditions. LTB4 and LTE4 were extracted from media, quantfied by enzyme-linked immunosorbent assay (ELISA), normalized to tissue weight and presented as ng/mg tissue (means +/- SEMs). In arteries, baseline synthesis of LTB4 was 0.15+/-0.20 and increased to 0.96+/-0.04 on stimulation with 1.0 micromol/L A2318, and 1.74+/-0.25 with 0.1 mmol/L arachidonic acid (AA). In veins the corresponding values were 0.28+/-0.10, 2.50+/-0.51, and 5.36+/-0.70. Baseline production of LTB4 was higher in veins. LTE4 synthesis in arteries was 0.25+/-0.02, which increased to 0.42+/-0.05 with A23187, and further to 0.69+/-0.06 with AA. The corresponding values in veins were 0.23+/-0.05, 0.74+/-0.09, and 1.56+/-0.28. Baseline metabolism of LTE4 by the vessels was not different. Furthermore, stimulation of vessels with 50 nmol/L PAF led to over 3-fold increase in LTB4 and LTE4 metabolism by the vessels. Smooth muscle cells stimulated with A23187 metabolized LTB4 and LTC4, which was sequentially catabolized to LTD4 and LTE4. Generally, stimulated veins, whether vessels or smooth muscle cells, metabolized more leukotrienes. The selective 5-lipoxygenase inhibitor, AA-861, significantly attenuated synthesis of both leukotrienes. Western analysis of membrane protein showed gReater expression of 5-lipoxygenase in stimulated veins. Our data show that veins produce more leukotrienes due to greater expression of 5-lipoxygenase in the vessels, and suggest that veins of newborn lamb lungs may be more susceptible to LT-induced vascular reactivity in the pulmonary circulation.     

Effect of platelet-activating factor on glycogen metabolism in fetal rat lung

Platelet-activating factor (1-alkyl-2-acetyl-sn-glycero-3-phosphocholine, or PAF) has previously been shown to induce glycogenolysis in the perfused adult rat liver and in the lung and liver of 24 day (gestational age) fetal rabbits in utero. In the present report, the effect of PAF was examined in fetal rats that were intravenously injected (through the vitellin vein) at a stage in their gestational development characterized by rapid glycogen depletion and surfactant accumulation. At 24 h after PAF administration of 2.5 micrograms and 5.0 micrograms to 19.5- and 20.5-day-old fetal rats, respectively, the lung glycogen content decreased significantly. In contrast, the inactive enantiomer of PAF did not modify the glycogenolytic response in vivo. When [14C]glucose (5 muCi) and PAF (5 micrograms) were simultaneously injected through the vitellin vein of the fetus, the radioactivity incorporated into lung glycogen was reduced as compared with control fetuses receiving the vehicle alone. An additional effect of PAF was noted in experiments designed to correlate glycogen breakdown to surfactant phospholipid biosynthesis. An inhibition of [3H]choline uptake and incorporation into phospholipids of fetal human lung explants and fetal lung type II pneumonocytes was induced by PAF. It is concluded that PAF appears to be a potential inducer of glycogen breakdown in the fetal lung and the relationship of these findings to fetal lung maturation is discussed.     

Influence of a platelet-activating factor antagonist on severe pancreatitis in two experimental models

This study investigates the role of platelet-activating factor (PAF) in experimental pancreatitis. The concentration of PAF quantified in ascites of bile-induced pancreatitis by radioimmunoassay (RIA) ranged from 3.67 ± 0.39 pmol/mL 2 h to 0.954 ± 0.39 pmol/mL 10 h after injection of taurocholate. Administration of a potent PAF antagonist, WEB-2170, prior to injection of taurocholate prolonged mean survival time in rats receiving iv camostate and albumin (46.4 h,n = 15, vs controls 38.3 h,n = 13). However, the survival rate after 72 h was not improved. The histologically estimated severity of pancreatitis and pancreatic enzymes in blood, tissue, or ascites was not affected. WEB-2170 had no effect on survival when injected simultaneously with taurocholate into the pancreatic duct or given iv after induction of pancreatitis (1, 0.1, or 0.01 mg/kg WEB-2170 vs controls). Subcutaneous injection of 10 mg/kg WEB-2170 also did not improve survival in pancreatitis induced by choline-deficient, ethionine-supplemented diet in mice. It is concluded that administration of a PAF antagonist after the onset of severe experimental pancreatitis does not influence its outcome, although activation of PAF may play a role in the pathogenesis of pancreatitis.     

Effects of hepatic inflow occlusion on changes in plasma potassium, histamine, and norepinephrine in rats.

To evaluate the effects of hepatic inflow occlusion without the shunt, the physiological differences were compared in three groups of rats in which the hepatoduodenal ligament was occluded for 15 min, 30 min, and 60 min. The survival rate significantly decreased in the 60 min occlusion group (53.6%) when compared with that of the 15 min and 30 min occlusion groups (95% and 91.6%, respectively). The significant differences in the changes in blood pressure (BP), the values of plasma potassium, histamine (HIS), norepinephrine (NE), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and the values of hematocrit (HT) were also observed between the 30 min and 60 min occlusion groups. The results indicate that, in rats, there is a high probability of an irreversible state to shock after 30 min hepatic inflow occlusion when veno-venous bypass is not applied. The values of plasma HIS and NE and the values of HT in portal blood were significantly greater than those in the general circulation. The results suggest that splanchnic congestion may have a greater influence than hepatic ischemia has in contributing to the deterioration of the physiological state.     

保留半肝动脉血供的入肝血流阻断法对大鼠肝缺血再灌注损伤的影响

目的:探讨保留半肝动脉血供的入肝血流阻断法对大鼠肝血缺再灌注损伤的影响.方法:将96只Wistar大鼠随机分为Pringle法Ⅰ组、半肝阻断Ⅱ组和保留半肝动脉血供的入肝血流阻断Ⅲ组.阻断肝血流30 min后,去血管夹恢复血流,分别于再灌注后1,2,6,24 h,抽血检测ALT和AST水平,然后取肝组织用于检测肝脏超氧化物歧化酶(SOD)及丙二醛(MDA)含量、肝脏病理学及肝细胞凋亡.结果:与Ⅰ组比较Ⅱ组和Ⅲ组再灌注后各时间点,ALT,AST,肝组织MDA含量及细胞凋亡率显著降低,肝组织SOD活力明显升高.Ⅲ组肝功改变、肝组织MDA含量、SOD活力及肝细胞凋亡率与Ⅱ组之间无显著差异(P>0.05).结论:保留半肝动脉血供的入肝血流阻断法对肝脏缺血再灌注损伤轻,效果好,操作简单,因而优于半肝血流阻断法.     

Protective effect of vitamin E on age-related alterations of Kupffer cell energy metabolism

AIM: To investigate the mechanism of age-related reduction of Kupffer cell (KC) phagocytic capacity and the protective management.METHODS: Using rhodamine 123 fluorescence density and rate of glucose utilization as parameters, we measured the mitochondrial energy metabolism status in vitro and the glucose utilization capacity of isolated rat liver Kupffer cells (KCs) from rats of various ages (6 mo, 12 mo, 18 mo and 24 mo) and the effect of vitamin E (VE) pretreatment (500 mg/kg/wk × 13 wk).RESULTS: The rate of KC glucose utilization and the rhodamine fluorescence density of KC mitochondria of 18 mo-old untreated rats (NVEG) were significantly lower than that of 6 mo-old NVEG by 19.3% (4.0 nmol·h ± 0.4 nmol·h^-1 10.6 cells^-1 vs 5.7 nmol·h ± 0.6 nmol·h^-1 10⁶ cells^-1, P < 0.05) and 19.5% (80.5 ± 6.3 vs 100.0 ± 4.7, P < 0.01) respectively; Rate of KC glucose utilization and the rhodamine fluorescence density of KC mitochondria of 6 mo-old rats were also lower than the 24 mo-old NVEG by 35.1% (3.7 nmol·h ± 0.6 nmol·h^-110⁶ cells^-1 vs 5.7 nmol·h ± 0.6 nmol·h^-1 10⁶ cells^-1, P < 0.01) and 32.1% (67.9 ± 7.4 vs 100.0 ± 4.7, P < 0.01) respectively. The two parameters of 18 mo-old VE pretreated rats (VEG) were significantly higher than those of 18 mo-old NVEG, and statistically comparable to those of 6 mo-old VEG. The two parameters of the 24 mo-old VEG were significantly higher in comparison with those of 24 mo-old NVEG, but still significantly lower than those of 6 mo-old VEG.CONCLUSION: Aging has a significantly negative effect on KC energy metabolism, which can be alleviated by VE pretreatment.     

The effects of nitric oxide on shock caused by temporary hepatic inflow occlusion in pigs

BACKGROUND/AIMS: Nitric oxide (NO) plays an important role in the regulation of systemic hemodynamics in various shock status. The effect of NO on shock induced by hepatic inflow occlusion has not been previously investigated. METHODOLOGY: We examined the effects of NO on systemic hemodynamics and oxygen metabolism in shock caused by temporary hepatic inflow occlusion without bypass in pigs using NO synthase inhibitor, NG-nitro-L-arginine methyl ester (NAME group) and the substrate for NO synthesis, L-arginine (ARG group). RESULTS: All animals in the control and ARG group tolerated the surgery, while 2 of 5 animals in the NAME group died during the occlusion period. Cardiac output and mixed venous oxygen saturation (SvO2) in the NAME group was significantly reduced compared with the other two groups during and after hepatic inflow occlusion. In contrast, SvO2 in the ARG group was maintained at higher levels throughout the study period, and the recovery time of cardiac output following reperfusion was earlier than that of the other two groups. CONCLUSIONS: Endogenous NO inhibition exacerbates the shock status induced by hepatic inflow occlusion. Exogenous administration of NO donor may improve the shock status induced by hepatic inflow occlusion.     

The possible role of platelet-activating factor antagonist therapy in the management of severe acute pancreatitis.

The purpose of this chapter is to examine the possible role of platelet-activating factor (PAF) antagonist therapy as a means of modifying the systemic inflammatory response syndrome (SIRS) and multi-organ dysfunction syndrome (MODS) in the management of patients with severe acute pancreatitis (AP). Supposed specific treatments of AP have not shown clinical benefit, with antiprotease agents such as aprotinin and gabexate mesilate, as well as fresh frozen plasma, being ineffective. In addition, early peritoneal lavage, intravenous glucagon, somatostatin and octreotide have shown no benefit.