Effects of hepatic ischaemia/reperfusion injury in a rabbit model of Indocyanine Green clearance

Hepatic ischaemia/reperfusion (I/R) injury is a major cause of primary non-function of the graft after liver transplantation. The ability to assess the severity of ischaemic injury would be of prognostic value and allow the possibility of therapeutic interventions. Currently there is no reliable clinical method for assessing the severity of hepatic ischaemic injury. The hepatic handling of Indocyanine Green as a technique for monitoring the severity of I/R injury has been investigated in the present study. A rabbit model of lobar ischaemia was used. At laparotomy, left lobe hepatic ischaemia was produced for 30, 45 or 60 min, followed by 60 min of reperfusion. Liver function tests, bile excretion and flow in the hepatic microcirculation were measured in animals subjected to I/R injury and in controls. Indocyanine Green was given after reperfusion and its concentration was measured directly in the liver using near-infrared spectroscopy. Indocyanine Green hepatic uptake and excretion rates were calculated. I/R injury produced significant increases in hepatic serum enzymes and decreases in bile excretion and hepatic microcirculation in all I/R groups in comparison with controls. There was a significant reduction in Indocyanine Green uptake and excretion in the I/R groups in comparison with controls, which was correlated with the duration of ischaemia. Indocyanine Green uptake was correlated significantly with flow in the hepatic microcirculation, and its excretion was correlated significantly with the severity of liver damage, as reflected by the changes in serum enzymes and bile excretion. In conclusion, I/R injury affects the hepatic handling of Indocyanine Green, and direct quantification of the uptake and excretion of this dye by near-infrared spectroscopy may be used to objectively assess the degree of I/R injury.     

声辐射力脉冲成像技术定量评价兔肝缺血后弹性改变的实验研究

目的 运用声辐射力脉冲成像(acoustic radiation force impulse,ARFI)技术评价兔肝门脉主干及肝固有动脉同时阻断后的弹性改变.方法 通过同时阻断肝门脉及肝固有动脉的方法建立兔肝缺血模型,运用ARFI技术分别于肝缺血前(T0)及缺血后5 min(T1)、20 min(T2)、30 min(T3)对兔右肝同一部位进行检查,测量肝缺血过程中肝组织的弹性;在相应时间点测定血清门冬氨酸氨基转移酶(AST)、丙氨酸氨基转移酶(ALT)水平,以及肝穿刺活检;最后进行统计分析.结果 T2兔右肝ARFI测值即组织剪切波速度(Vs)明显高于T0,差异有统计学意义(P＜0.05),T3兔右肝Vs明显高于T2,差异有统计学意义(P＜0.05);T2血清AST、ALT水平稍高于T0,但差异无统计学意义(P＞0.05),T3血清AST、ALT水平明显高于T2,差异有统计学意义(P＜0.05);组织学观察在T2、T3可见兔肝缺血损伤病理改变.结论 ARFI技术定量分析缺血肝组织弹性改变能在较早期准确、客观地反映肝缺血损伤的严重程度.     

术中肝门阻断对肝细胞肝癌合并门静脉分支癌栓患者肝功能的影响

目的：探讨肝细胞肝癌（HCC）合并门静脉分支癌栓（portal vein tumor thrombosis,PVTT）患者术中肝门阻断对术后肝功能恢复的影响.方法：选择2012年6月-2013年4月收治的HCC患者39例,其中合并及不合并PVTT的患者分别为18例和21例,在肝门阻断下行肝段以上的肝脏切除术,比较其术后肝功能恢复情况.结果：两组患者肝硬化分级、肝门阻断时间及手术时间差异有统计学意义.两组患者术后1、3、5天的总胆红素、丙氨酸氨基转移酶、天门冬氨酸氨基转移酶、凝血酶原时间比较,差异无统计学意义;HCC合并PVTT组患者术后第1、3天的前白蛋白及第1天的白蛋白分别为（0.14±0.04）、（0.09±0.14）和（37.17±3.19）g/L,与HCC不合并PVTT组患者[（0.19±0.05）、（0.11±0.04）、（39.48±3.16）g/L]比较,差异有统计学意义（P值分别为0.002、0.02及0.03）.结论：HCC合并PVTT患者术中行肝门阻断安全有效,术后患者肝脏合成前白蛋白的能力较不合并PVTT患者短期下降更明显,在术后第5天均未恢复正常,需加强保肝治疗.     

新型肝脏止血捆扎带的动物实验

背景：课题组设计了一种尼龙搭扣肝止血捆扎带,比原有的止血带在技术上有创新,解决了临床使用中容易滑脱的问题,且使用更加简便。目的：观察新型肝脏止血捆扎带与全肝和半肝血流阻断法在肝切除中的效果比较。方法：健康家兔分别采用全肝血流阻断法切肝、半肝血流阻断法切肝及用新型肝脏止血捆扎带捆扎后切肝。比较术中肝脏缺血时间、手术时间、术中出血量,术前及术后第1,3,7天谷丙转氨酶、谷草转氨酶水平的变化。结果与结论：新型肝脏止血捆扎带组在手术时间和术中出血量上明显减少,且在术后第1天和术后第3天谷丙转氨酶和谷草转氨酶水平的升高幅度较其他两组低,但1周后均可恢复正常水平。结果提示该新型肝脏止血捆扎带术中操作简便,捆扎止血效果更为可靠,对肝功能损害较轻,是一种安全、有效、可行的新的肝切除方法。     

肝血流阻断在肝囊性包虫病手术中的应用

目的 探讨不同肝血流阻断方法在肝囊性包虫病手术中的临床效果。 方法 回顾性分析近2年来手术中使用了入肝血流阻断的42例肝囊性包虫病患者的资料,依照入肝血流阻断方法分成2组:第一肝门阻断法（Pringle法）组24例和半肝血流阻断法组18例,比较其手术时间、血流阻断时间、出血量、术后5 d内血谷氨酸氨基转移酶、总胆红素峰值和术后并发症发生情况。 结果 半肝血流阻断组在术中出血量、术后肝功能方面优于Pringle法组（P<0.05）,两组在手术时间、血流阻断时间及术后并发症方面的差异无统计学意义（P>0.05）。 结论 合适的入肝血流阻断方法在肝囊性包虫病手术中具有重要意义,具体采用Pringle法或半肝血流阻断法应根据患者病情、术中探查及医疗水平进行合理选择。       

肝脏外科血流阻断与重建：技术进展及研究热点

背景：在肝移植手术中,肝脏外科血流阻断技术很重要,它可减少术中出血,有利于肝功能恢复等优点。在肝脏外科技术的发展中,出现了各种优良的肝脏血流阻断技术,该技术领域至今仍是外科界的研究热点。目的：介绍了肝脏外科血流阻断技术种类,最新研究热点及进展。方法：以“Hepatectomy;Hepatic vascular exclusion;Advancement”及“肝切除术;血流阻断”为检索词,分别检索PubMed数据库和万方医学网1999年1月至2014年1月相关文献。选择与入肝血流阻断、择性入肝血流阻断、全肝血流阻断及肝切除断面血流阻断技术相关的文献50篇文献进行分析探讨。结果与结论：肝脏血流阻断方法种类较多,最常用的是间歇入肝血流阻断法和半肝入肝血流阻断法。建议的适用原则是：①对于在肝脏边缘的病灶小于5 cm的患者,可考虑在不阻断肝脏血流的情况下进行手术。②局限于半肝内的病灶适合半肝入肝血流阻断法,尤其适合合并肝硬化的患者,保留半肝动脉入肝血流阻断法和绕肝提拉肝血流阻断法的也有相关的研究,认为在临床应用具有一定价值,但从目前来看二者的临床研究报道相对较少,有待进一步研究。③超过半肝或跨越两半肝（巨大病灶）的病灶适合用间歇入肝血流阻断法。④累及肝后下腔静脉和（或）肝静脉,或与第二、三肝门关系紧密的病灶适合用肝血流隔离法及其改良术式。⑤病灶体积较小局限于肝段内条件允许可考虑肝段血流阻断技术,还可用常规的半肝血流阻断法和入肝血流阻断法。根据病情的具体情况,选择适合的方法是减少出血、保证患者安全的关键。     

In vivo kinetics of microbubbles of SH U 508 A (Levovist): comparison with indocyanine green in rabbits

The aim of this study was to evaluate in vivo kinetics of microbubbles of SH U 508 A, in comparison with Indocyanine Green, a dye used as an indicator of blood flow. Microbubble kinetics were evaluated in various vessels (i.e., vena cava, aorta, renal artery, renal vein and portal vein) in rabbits after injection of SH U 508 A by measuring Doppler signals (n = 5). The kinetics of Indocyanine Green were evaluated by measuring absorbance using a photodiode (n = 5). Test substances (SH U 508 A 300 mg/mL and Indocyanine Green 1.25 mg/mL) were injected IV at a dose of 0.1 mL/kg B.W. Peak signal intensity was observed immediately after injection of SH U 508 A, followed by biphasic decay. The rates of biphasic decay were similar in all vessels. A second peak of the signal, which indicated recirculation of the microbubbles, was observed in the vena cava. The circulation and recirculation times of the microbubbles after injection of SH U 508 A were similar to that of Indocyanine Green. These findings suggest that the majority of SH U 508 A microbubbles circulate through the body similarly to blood flow, without retention, in the vasculature.     

Prostaglandin E1 improves hepatic encephalopathy produced by ischaemia-reperfusion liver injury in rats

OBJECTIVE: To investigate the action of prostaglandin E1 on hepatic encephalopathy. DESIGN: Prospective, randomised, controlled animal study. SETTING: University animal laboratory. SUBJECTS: Male Wistar rats. INTERVENTIONS: After passive avoidance learning, acute liver failure was induced by occlusion of the left portal vein and the hepatic artery for 90 min. Then memory retention was evaluated 48 h later. The effects of prostaglandin E1 on memory retention were examined in animals treated with the agent systemically (intravenous injections with prostaglandin E1 twice before and after surgery, 20 microg/kg each time) and animals treated with the agent topically (intracerebroventricular injection with prostaglandin E1, 0.1 microg/h for 48 h beginning at liver ischaemia). MEASUREMENTS AND RESULTS: Marked damage was found on plasma analysis in animals subjected to liver ischaemia, and the memory retention was also impaired. Intravenous administration of prostaglandin E1 improved both the liver injury and memory retention. However, intracerebroventricular administration of prostaglandin E1 alleviated neither. CONCLUSION: These findings show that prostaglandin E1 contributes to the amelioration of hepatic encephalopathy by improving liver function.     

A new experimental model of specific liver hypoxia using membrane oxygenator

The present study introduces a new experimental canine model of hepatic arterial deoxygenation using a membrane oxygenator to investigate the influence of hepatic arterial hypoxia on hepatic hemodynamics and energy metabolism. Eighteen mongrel dogs weighing 10 kg each were randomly divided into three groups: group A served as a control (118.0±9.0 mmHg of hepatic arterial O₂ content), group B as a moderately deoxygenated group (40 mmHg of hepatic arterial O₂ content), and group C as a severely deoxygenated group (25 mmHg of hepatic arterial O₂ content). Deoxygenation was achieved by perfusion of a gas mixture of O₂ and N₂ through the membrane oxygenator, which was interposed between the femoral artery and the proper hepatic artery, for 60 min. In group C, hypoxia decreased the mean systemic arterial blood pressure and hepatic arterial blood flow. Arterial blood ketone body ratio (AKBR=acetoacetate/3-hydroxybutyrate), which reflects the hepatic mitochondrial redox state, rapidly decreased prior to the significant increase of glutamate oxaloacetate transminase, glutamate pyruvate transminase, and lactate dehydrogenase after the initiation of hypoxia. Hepatic arterial deoxygenation to 25 mmHg for 60 min induced injury to hepatic hemodynamics, resulting in the deterioration of systemic hemodynamics even after the termination of liver hypoxia. This in vivo temporal hepatic arterial hypoxic model without alteration of inflow volume might be useful for investigating the mechanism of hypoxic injury and the critical point of liver hypoxia on hepatic and/or systemic hemodynamics and liver viability.     

Direct and indirect measurement of the hepatic extraction ratio of indocyanine green in the rat

1. In order to estimate liver blood flow in the rat, the extraction ratio of Indocyanine Green was determined using a two-compartment model fitted to the plasma concentration time data after a single intravenous bolus dose and compared with values obtained directly by transhepatic sampling, both in the intact rat and in an isolated perfused rat liver preparation. 2. There was no agreement between estimates of the extraction ratio obtained by using the kinetic model and the directly measured values. 3. Elimination curves for Indocyanine Green were simulated to yield varied clearance values. Despite a 250% variation in clearance, extraction ratios derived using the two-compartment model were all greater than 0.9 and varied by less than 6%. 4. Estimates of liver blood flow obtained by deriving a value of the extraction ratio of Indocyanine Green using the two-compartment model are inaccurate.     

Hepatic blood flow and metabolism in severe falciparum malaria: clearance of intravenously administered galactose.

1. Hypoglycaemia and lactic acidosis are important manifestations of severe falciparum malaria. To investigate hepatic gluconeogenesis in acute falciparum malaria, liver blood flow and galactose clearance were estimated in seven adult patients with moderately severe infection and seven patients with severe infection (three of whom died later). Nine patients were restudied in convalescence. 2. Liver blood flow, determined from the plasma clearance of Indocyanine Green, was lower in acute illness than in convalescence [16.1 (7.0) versus 23.9 (7.2) ml min-1 kg-1, mean (SD)], but this difference was not statistically significant (P = 0.15). There was a significant inverse correlation between admission venous plasma lactate concentrations and the liver blood flow estimated from the clearance of Indocyanine Green (rs = 0.71, P = 0.004). 3. The plasma clearance of galactose after intravenous injection was similar in the acute [15.4 (4.90) ml min-1 kg-1] and convalescent study [12.8 (2.1) ml min-1 kg-1]. The ratio of galactose clearance to Indocyanine Green clearance was significantly higher in acute disease [1.41 (0.51)] than in convalescence [0.70 (0.34)], largely because of the elevated ratios in severely ill patients [1.48 (0.50)]. 4. The rise in blood glucose concentration after galactose administration was significantly higher during acute illness [1.48 (0.72) mmol/l] than in convalescence [0.67 (0.41) mmol/l, P = 0.022], but the insulin response was similar, indicating reduced tissue insulin sensitivity. There was no significant change in the plasma concentrations of other metabolites (lactate, pyruvate, alanine and triacylglycerol) in either study. 5. These results suggest that the segment of the glycolytic pathway between galactose and glucose is unimpaired in patients with severe falciparum malaria.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of prior portosystemic shunt on early hepatic hemodynamics and sinusoids following 84% hepatectomy in dogs

The effects of a prior portosystemic shunt (PSS) on the hepatic hemodynamics and sinusoids shortly after an 84% hepatectomy (Hx) were investigated in dogs. Fifteen mongrel dogs were divided into three groups, a 70% Hx group (n=5), an 84% Hx group (n=5) and an 84% Hx+PSS group (n=5). In the last group, a shunt was inserted between the splenic and femoral veins prior to the hepatectomy. The systemic and hepatic hemodynamics were measured, before and 180 min after the hepatectomy, and the remaining liver tissue was then examined immuno-histochemically by light microscopy using the thrombomodulin (TM) staining method. The postoperative portal vein pressure and the vascular resistance were significantly lower in the PSS group than in the 84% non-PSS group. The total postoperative hepatic blood flow was higher in the 84% non-PSS group than in the other two groups. Immunohistochemical observation after TM staining indicated that the sinusoidal endothelial cells in the 84% non-PSS group were markedly damaged 3 h after surgery. We conclude that a prior PSS improves the hepatic hemodynamics and is beneficial to the sinusoids within the first few hours of an 84% hepatectomy in dogs.     

新型肝脏止血捆扎带的动物实验

背景:课题组设计了一种尼龙搭扣肝止血捆扎带,比原有的止血带在技术上有创新,解决了临床使用中容易滑脱的问题,且使用更加简便。目的:观察新型肝脏止血捆扎带与全肝和半肝血流阻断法在肝切除中的效果比较。方法:健康家兔分别采用全肝血流阻断法切肝、半肝血流阻断法切肝及用新型肝脏止血捆扎带捆扎后切肝。比较术中肝脏缺血时间、手术时间、术中出血量,术前及术后第1,3,7天谷丙转氨酶、谷草转氨酶水平的变化。结果与结论:新型肝脏止血捆扎带组在手术时间和术中出血量上明显减少,且在术后第1天和术后第3天谷丙转氨酶和谷草转氨酶水平的升高幅度较其他两组低,但1周后均可恢复正常水平。结果提示该新型肝脏止血捆扎带术中操作简便,捆扎止血效果更为可靠,对肝功能损害较轻,是一种安全、有效、可行的新的肝切除方法。     

肝癌切除患者术后并发症的原因分析及对策

目的分析肝癌切除术后影响并发症出现的危险因素。方法对110名肝癌切除患者术后出现的并发症进行回顾性总结,选取11个可能因素,分别进行单因素及logistics分析,分析各因素与术后并发症之间的关系。结果110例肝癌切除患者,术后出现并发症38例（34．5％）,对可能影响并发症的各因素行单因素统计分析,结果表明,术前HBV DNA水平、术前Child分级、前白蛋白水平、PT情况、肝门阻断与否、术中出血量等6个因素和术后出现并发症有显著相关,而年龄、性别、有无附加手术、有无基础疾病、BMI等因素则和术后出现主要并发症无明显相关。将上述单因素分析中与术后并发症显著相关的6个因素再进行logistic多因素回归分析,结果表明术前Child分级、前白蛋白水平、术中出血量是术后出现主要并发症的独立危险因素。结论肝癌手术的并发症情况主要受术前肝功能储备情况及术中出血量等因素影响。     

Cardiac function in open-chest dogs after left to right ventricular shunting and right coronary artery occlusion

Summary. Patients with acquired ventricular septal defect (VSD) after myocardial infarction have a particularly bad prognosis if right ventricular function is severely impaired. The significance of an ischaemic right ventricular free wall on cardiac function during interventricular shunting was examined in open-chest dogs. An external interventricular shunt could be opened and closed at will, and by occlusion of the right coronary artery (RCA), a part of the right ventricular free wall was rendered ischaemic. Aortic flow decreased by 8±2% when the shunt was opened in the presence of a normal right ventricle, and by 16±2% (difference: P<0.05) in the presence of right ventricular ischaemia. Aortic flow fell by 19±3% when the RCA was occluded. Right ventricular dyskinesia was demonstrated after occlusion of RCA, by recording segment lengths in the right ventricular free wall. The dyskinesia was aggravated when the shunt was opened. The left ventricle exerted a ‘negative’ work on the ischaemic right ventricular free wall. Retention of blood in the right ventricle, with a subsequent decline in left ventricular filling and an almost unchanged interventricular shunting of blood, explain why aortic flow fell more when the shunt was opened in the presence of right ventricular ischaemia.     

Clinical value of hepatic vein catheterization

Techniques of hepatic vein catheterization, hepatic venous pressure measurement, and occlusion phlebography using a balloon catheter are described.Hepatic venous pressure measurements (n=95) and hepatic occlusion phlebography were combined in 32 cases.In patients with liver cirrhosis (n-63) a significant elevation of hepatic venous pressure gradients was found. A decrease of the pressure gradient was seen after portacaval and splenorenal shunt operations.Hepatic occlusion phlebography showed alterations of hepatic veins only in patients with cirrhosis. A rough correlation between pressure gradients and the extent of changes in the liver veins was found. Hepatic occlusion phlebography, in patients who had undergone shunt procedure, demonstrated various collaterals.Combined hepatic vein pressure measurements and hepatic occlusion phlebography using a balloon catheter are proposed as a very suitable method for the evaluation of chronic liver disease and portal hypertension.     

腹腔镜肝切除术下展开肝主流阻断技术治疗原发性肝癌的疗效观察

目的研究腹腔镜肝切除术下展开肝主流阻断技术治疗原发性肝癌的疗效。方法回顾性选择2018年9月至2020年2月于新疆医科大学第一附属医院行腹腔镜肝切除术且未中转开腹患者162例,其中采用全入肝血流阻断技术52例为A组,半肝血流阻断技术54例为B组,半肝血流阻断加肝静脉控制技术56例为C组。比较3组疗效指标[术后通气时间,引流管留置时间,肝功能指标丙氨酸氨基转氨酶(ALT)、天冬氨酸氨基转氨酶(AST)、总胆红素(TBIL)水平,治愈率]和安全性指标(手术指标:手术时间、术中出血量、输血率,术后并发症发生率、病死率)。结果C组术中出血量[(148.77±31.33)mL]、术中输血率(3.57%)低于A、B组[(198.02±40.14)mL、9.26%;(229.63±48.36)mL、11.54%],差异有统计学意义(P<0.05)。B组术中出血量和术中输血率均低于A组,差异有统计学意义(P<0.05)。术后3 d,B、C组ALT、AST、TBIL水平[(90.35±38.87)U/L、(85.56±20.11)U/L、(22.12±3.96)μmol/L;(88.98±35.46)U/L、(87.74±20.13)U/L、(21.37±4.01)μmol/L]均低于A组[(201.03±58.62)U/L、(129.99±34.58)U/L、(36.63±4.57)μmol/L],差异均有统计学意义(P<0.05)。B、C组术后通气时间、引流管留置时间、术后住院时间[(22.41±3.54)h、(9.03±1.06)d、(10.11±2.06)d;(20.55±3.48)h、(8.77±0.98)d、(10.02±2.03)d]低于A组[(30.22±4.65)h、(9.96±1.22)d、(11.54±2.30)d],差异均有统计学意义(P<0.05),而治愈率(81.48%、87.50%)高于A组(57.69%),差异有统计学意义(P<0.05)。3组病死率分别为1.92%、0、0,差异无统计学意义(P>0.05)。C组术后总并发症发生率(3.57%)低于A组(26.92%),差异有统计学意义(P<0.05)。结论半肝血流阻断加肝静脉控制法可有效保护残肝肝功能,有效控制术中出血,提高了患者术后恢复、治愈率,减少了术后并发症发生。     

Opioid effects on hepatic disposition of dyes in mice

Morphine administration acutely reduced plasma clearance of sulfobromophthalein (BSP) in mice and increased hepatic retention of this dye. Increasing morphine doses from 5 to 40 mg/kg s.c. progressively raised plasma and liver BSP levels. Morphine-treated mice, warmed to reverse hypothermia, still had higher plasma and liver BSP levels. The narcotic also raised plasma levels of two dyes which are not conjugated, indocyanine green and dibromosulfophthalein. Naloxone reversed morphine-induced elevation of plasma BSP levels. In bile duct-ligated mice, plasma BSP levels were very high but hepatic BSP levels remained low, both after saline or morphine. Thus, the effects of morphine on BSP disposition differed from those of biliary occlusion. BSP content in bile was reduced by morphine, as dye levels were raised in plasma and hepatic parenchyma. In bile duct-cannulated mice morphine increased BSP levels in plasma and liver whereas reducing the amount of dye eliminated in bile.     

Functional deterioration of the liver by elevated inferior vena cava pressure: A proposed upper safety limit of pressure for maintaining liver viability in dogs

Objective Abnormally elevated central venous pressure is considered to be an etiological factor in the onset of acute hepatic failure following modified Fontan operation. This paper hypothesises that an increase in inferior vena cava pressure (IVCP) after such an operation has adverse effects on hepatic energy status.Design Various degrees of venous hypertension were produced in 10 mongrel dogs by clamping the thoracic IVC with an active veno-venous shunt and varying its flow rate from 60–2.5 ml/min/kg. Arterial ketone body ratio (KBR), reflecting the hepatic mitochondrial redox state, was measured as an index of hepatic energy status.Measurements and results: The lower the flow rates of the shunt, the higher the pressures of IVC and portal vein, while systolic blood pressure was maintained above 100 mmHg. CO significantly decreased when the pump speed was less than 30 ml/min/kg. KBR showed a negative correlation to IVCP as well as a positive correlation to portal blood flow (p<0.05).Conclusion From the simple regression line obtained between IVCP and KBR, it was determined that an upper safety limit of IVCP may lie at about 27 cmH₂O (20.5 mmHg), and that a IVCP of 35 cmH₂O (26.6 mmHg) seems to be the critical level for maintaining liver viability.Supported in part by grants from the Scientific Research Fund of the Ministry of Education and a Grant-in-Aid for Cancer Research from the Ministry of Health and Welfare, Japan