慢性肝炎肝硬化和肝衰竭患者吲哚菁绿清除试验的变化及其临床意义

目的 探讨吲哚菁绿(ICG)清除试验对不同程度慢性肝病患者肝脏储备功能的评估价值。方法 2017年11月～2019年8月山西医科大学第一医院感染病科住院治疗的肝病患者87例,其中慢性病毒性肝炎9例,肝硬化69例,慢性肝衰竭9例,使用日本DDG-3300K分析仪及配套分析软件检测ICG15分钟滞留率(ICG-R15)、ICG血浆清除率(K值)和有效肝脏血流量(EHBF),同时检测肝功能、血常规、腹部彩超、腹部CT或MRI,计算肝功能Child-Turcotte-Pugh(CTP)评分并对肝硬化患者分级。结果 慢性肝衰竭组ICG-R15为(54.2±11.6)%,K值为(0.04±0.01)/min,EHBF为(0.2±0.1)L/min,与慢性肝炎组比,差异显著【分别为(7.4±1.7)%、(0.22±0.05)/min和(0.9±0.3)L/min,P<0.05】;11例CTP C级患者ICG-R15为(39.3±8.9)%,K值为(0.06±0.02)/min,EHBF为(0.3±0.1)L/min,与39例CTP B级【分别为(28.8±12.6)%、(0.10±0.03)/min和(0.4±0.2)L/min,P<0.05】或19例CTP A级【分别为(12.2±2.8)%、(0.16±0.05)/min和(0.7±0.2)L/min,P<0.05】比,差异显著。结论 ICG清除试验能动态反映肝脏储备功能,弥补CTP分级的不足,尝试作为早期诊断肝硬化的参考指标,值得进一步研究。     

吲哚菁绿清除试验对乙型肝炎肝硬化患者肝脏储备功能的评估价值

目的通过吲哚菁绿(ICG)清除试验评估乙型肝炎肝硬化患者肝脏储备功能,探讨ICG清除试验与Child-TurcottePugh(CTP)分级和MELD评分评价肝功能之间的关系。方法收集福建医科大学附属第一医院2012年1月-2015年1月住院的乙型肝炎肝硬化患者127例,进行ICG清除试验,计算患者的ICG血浆清除率值(K值)、有效肝血流量(EHBF)、ICG 15 min滞留率(ICG R15),以及CTP分级和MELD评分。组间比较采用方差分析,进一步两两比较采用LSD-t检验;相关性比较采用Spearman等级相关性分析;采用受试者工作特征曲线下面积(AUC)比较肝脏储备功能。结果乙型肝炎肝硬化患者CTP分级:A级患者63例,B级患者45例,C级患者19例。随着CTP分级升高,ICG R15逐渐增高,而EHBF和K值则逐渐降低,差异均有统计学意义(F值分别为146.96、91.26、40.94,P值均分别为0.001、0.003、0.005)。在评价肝功能方面ICG R15与MELD评分及CTP分级呈正相关(r值分别为0.525、0.838,P值均0.01),与EHBF及K值呈负相关(r值分别为-0.703、-0.901,P值均0.01)。ICG R15AUC为0.85,MELD评分AUC为0.65。结论 ICG消除试验能够准确动态反应肝脏储备功能,ICG R15评估肝脏储备功能优于CTP分级及MELD评分。     

急性肝内窦前型门静脉高压症大鼠肝内门体分流的变化及其意义

目的探讨急性肝内窦前型门静脉高压症时肝内门体分流的变化及其意义。方法经大鼠门静脉注射乳胶微球造成急性肝内窦前型门静脉高压症。采用肝山梨醇摄取率法测定功能性肝血流量和肝内门体分流量,采用放射性微球法测定肝内较大门体分流侧支(直径>15μm)的分流率。结果对照组肝山梨醇摄取率为(97.9±0.5)％,肝总血流量为每100g体重(2.52±0.23)ml／min。微球组,肝山梨醇摄取率锐减至(12.8±4.3)％,微球加肝动脉结扎组则下降至(4.1±0.7)％,t值为3.541和3.668,P值均<0.01;肝内门体分流量对照组、微球组、微球加肝动脉结扎组分别为每100g体重(0.06±0.02)、(1.46±0.15)和(1.16±0.19)ml／min,t值分别为5.468和6.869,P值均<0.01;门静脉血流量3组差异无统计学意义。结论肝内门体分流的直径大多<15μm。其开放可使70％的门静脉血绕过肝窦而直接注入肝静脉,并有效阻止了门静脉压力的升高。     

应用吲哚氰绿计算人体肝血流及清除率的方法学问题

肝血流对肝功能有重要意义,亦关系到肝脏的生理学及临床药理学问题。测定肝血流率(Q)历来采用Bradly等倡导的方法,即持续滴注一种染料(多用吲哚氰绿ICG)(i),再测定周围动脉(A)及肝静脉血(V)中的ICG浓度;Q=(A-V)/A,按Fick’s原理计算而得。其后有人将其简化为持续滴注或单剂注入ICG后测算清除率(CI)来表示肝血流率,假定ICG在体内完全由肝脏摄取。但该项测算受方法学的限制,其合理性须待验证,例如在持续滴注中不能保证稳态(不与时间相关的ICG浓度),ICG血浓度常可随时间而增高。本文目的为验算这种非稳态的持续滴注对计算肝血流率及ICG清除率的影响,进而重新评价ICG清除率作为肝血流率的可行性。研究方法:计算浓度-时间曲线,用线性回归方法评定,取得动脉(A)及静脉(V)的平均ICG浓度及     

乙型肝炎肝硬化患者的吲哚箐绿清除试验与Child-Pugh分级相关性的研究

目的对吲哚箐绿(ICG)清除试验与Child-Pugh评分进行对比研究,评估临床应用价值,探讨两者的相关性。方法选择2016年1月至2017年4月在青海省第四人民医院肝病科住院的101例患者,其中慢性乙型肝炎(CHB)41例,乙型肝炎肝硬化60例(Child-Pugh A级27例,Child-Pugh B级33例)。比较各组的ICG清除试验指标[ICG血浆清除率值(K值)、有效肝血流量(EHBF)、ICG 15 min滞留率(ICG R15)]、Child-Pugh分级、肝脏血清生物化学指标[总胆红素(TBil)、白蛋白(Alb)、凝血酶原时间(PT)],并分析ICG清除试验与Child-Pugh分级的相关性。结果 CHB组的ICG R15、K值、PT、Alb与肝硬化组比较,差异均有统计学意义(P均0.05);两组的EHBF、TBil比较,差异无统计学意义;肝硬化组中,Child-Pugh A级组与Child-Pugh B级组比较显示,随着Child-Pugh分级升高,ICG R15、PT、TBil水平升高,而K值、EHBF、Alb水平下降,差异均有统计学意义(P均0.05);ICG R15的受试者工作特征(ROC)曲线下面积(AUC)为0.827,截断值为13.3%时,敏感度为71%,特异度为85.2%;PT的AUC为0.886,截断值为14.4 s时,敏感度为71%,特异度为88.9%。结论 ICG清除试验与Child-Pugh评分和肝脏生物化学指标存在相关性,ICG R15与PT联合应用可能可以更好地评估肝功能储备。     

慢性肝病肝脏储备功能与肝纤维化的关系

目的:研究慢性乙型肝炎及乙肝肝硬化患者的肝脏储备功能及肝纤维化,进一步探讨肝脏储备功能与肝纤维化之间的关系.方法:60例慢性乙肝病毒感染患者,分为慢性乙型肝炎及乙肝肝硬化代偿期两组,利用脉冲式色素浓度图像分析仪(DDG)行吲哚氰绿(ICG)排泄试验,监测ICG血浆清除率(K)和15min滞留率(R15);同时利用Fib...     

血吸虫病性肝硬化患者腹部CT表现和CT定量参数特征观察*

目的 探讨血吸虫病性肝硬化患者腹部电子计算机断层扫描(CT)表现和CT定量参数特征。方法 2018年5月～2020年5月我院收治的血吸虫病性肝硬化患者72例,其中Child-Pugh A级26例、Child-Pugh B级21例和Child-Pugh C级25例,另选择同期于我院健康体检者25名。使用飞利浦64排CT行上腹部平扫和增强扫描,选择感兴趣区,获取肝灌注参数血容量(BV)、血流量(BF)、平均通过时间(MTT)、肝动脉分数(HAF)和肝动脉灌注量(HAP)。结果 72例血吸虫病性肝硬化患者出现较典型的肝硬化CT表现、肝功能损伤的血生化学改变和脾功能亢进症表现;健康人腹部CT灌注参数BV、BF、MTT、HAF和HAP分别为(47.3±8.2)ml/100g、(211.9±42.1)ml/min/100g、(12.9±3.1)s、(0.2±0.0)和(16.3±7.9)ml/min/100g,Child-Pugh A级患者分别为(40.8±7.6)ml/100g、(183.1±37.2)ml/min/100g、(15.8±3.7)s、(0.3±0.0)和(19.1±8.8)ml/min/100g,Child-Pugh B级患者分别为(35.5±6.9)ml/100g、(124.7±33.2)ml/min/100g、(19.2±4.5)s、(0.3±0.0)和(24.5±9.9)ml/min/100g,Child-Pugh C级患者分别为(24.8±8.4)ml/100g、(115.5±28.1)ml/min/100g、(24.6±5.5)s、(0.4±0.1)和(33.5±12.5)ml/min/100g,各组间差异显著(P<0.05)。结论 对血吸虫病性肝硬化患者行CT检查能够了解肝脾形态学改变信息,测量CT灌注参数也能够为评估肝硬化的严重程度提供参考依据。     

脾腔小口径分流联合断流术对肝硬化门静脉高压症患者肝血流动力学和储备功能的影响

目的观察脾腔小口径分流联合断流术对肝硬化门静脉高压症患者肝血流动力学和肝储备功能的影响。方法 86例肝硬化门静脉高压症患者,分别行脾腔小口径分流联合断流术(联合组,58例)和贲门周围血管离断术(断流组,28例)。通过术中自由门静脉压力(FPP)监测和术后彩色多普勒超声检查明确不同手术方式对门静脉血流量(PVF)的影响,通过吲跺氰绿排泄试验(ICGR15)观察肝储备功能和有效肝血流量(FHF)的变化。结果联合组术后FPP、PVF、FHF和ICGR15分别为(31.4±2.4)cm H2O、(900±350)ml/min、(551±246)ml/min和(31.2±13.8)%,较术前有明显降低或升高【(38.2±3.6)cm H2O、(1250±360)ml/min、(696±300)ml/min和(23.6±11.9)%,P0.05】。断流组术后FPP、PVF,FHF和ICGR15为(32.8±3.2)cm H2O、(980±250)ml/min、(507±140)ml/min和(27.4±13.0)%,也较术前明显升高或降低【(36.9±3.9)cm H2O、(1320±320)ml/min)、625±158)ml/min和(22.2±13.4)%,P0.05】。与断流组比较,联合组FPP下降更为明显(P0.05),而PVF、FHF和ICGR15比较无显著性差异(P0.05)。术后30天联合组肝功能良好、轻度和重度代偿不全发生率为72.4%、19.0%和8.6%,断流组分别为67.9%、21.4%和10.7%,两者差异无显著统计学意义。随访5~36月,联合组分别有1例和4例发生上消化道出血和肝性脑病,断流组分别为3例和2例。结论脾腔小口径分流联合断流术治疗门静脉高压症是安全有效的,该术式在降低门静脉压力同时,可维持门静脉向肝血流,保护肝脏储备功能,防止肝功恶化衰竭。     

吲哚氰绿试验对老年人肝储备功能的评估

目的　探讨ICG试验对老年人肝储备功能的评估价值。方法　以标准方法检测老年健康人、老年慢迁肝患者、老年肝硬化患者及青年健康人血中ICG1 5min潴留率 (R1 5ICG)及消失率 (KICG)。结果　青年健康人、老年健康人、老年慢迁肝患者和老年肝硬化患者R1 5ICG分别为 (5 85± 1 36) %、(8 53± 1 0 1 ) %、(1 3 66± 1 80 ) %、(2 8 57± 4 51 ) % ,KICG分别为 0 31 0± 0 0 7、0 1 80± 0 0 1、0 1 59± 0 0 1、0 1 1 5± 0 0 0 1。健康青年人和健康老年人无明显差异 ;健康老年人较老年慢迁肝、老年肝硬化患者差异极显著。结论　ICG试验是评估老年人肝储备功能的良好指标     

温阳中药对肝纤维化大鼠血流动力学的影响

目的观察温阳中药对肝纤维化大鼠血流动力学的影响。方法制备大鼠肝纤维化模型,分为两组,治疗组给予温阳中药,对照组予等量等渗盐水,疗程结束后检测肝脏及肠系膜血流动力学指标、肝功能及肝组织羟脯氨酸含量。结果肝脏表面血流每100 g体重多普勒值:正常组为(21.9±1.3)ml/min, 模型对照组为(7.5±0.4)ml/min、未治疗对照组为(11.7±0.7)ml/min、治疗组为(16.0±0.8)ml/min, t值分别为30.776、20.333和11.513,P值均<0.01;肠系膜表面血流多普勒值:正常组为(40.9±1.8)ml/min、模型对照组为(26.1±0.9)ml/min、未治疗对照组为(30.3±1.2)ml/min、治疗组为(34.9±1.1)ml/min, 治疗组的恢复显著,不仅多普勒值明显高于模型对照组(t值分别为29.94 5和18.527,P<0.01),而且也明显高于未治疗对照组(t值分别为12.64 1和8.309,P<0.01);肠系膜微血管血流速度均明显大于未治疗对照组;同时,肝脏内羟脯氨酸含量显著下降,血清肝功能明显好转。结论温阳中药可改善肝脏及肠系膜的微循环,减少肝脏内的胶原沉积,改善肝细胞功能。     

Effect of portacaval shunt on drug disposition in patients with cirrhosis

To examine the consequences of liver blood flow variations on drug disposition in cirrhosis, we studied the effects of portacaval shunt on drug clearance in 35 cirrhotic patients. Lidocaine clearance and bioavailability, indocyanine green (ICG) clearance, aminopyrine breath test, and hepatic blood flow were measured before and 18 months after surgery. The patients were divided into two groups according to severity of disease: 14 patients (group 1) had slight liver dysfunction (ICG extraction ratio greater than 0.25) and 21 patients (group 2) had severe liver disease (ICG extraction ratio less than 0.25). After portacaval shunt the decrease in hepatic blood flow was similar for both groups (-65%). In group 1, ICG systemic clearance decreased from 9.10 +/- 0.68 to 4.40 +/- 0.34 ml/min . kg (p less than 0.05), whereas ICG intrinsic clearance remained unchanged; lidocaine systemic clearance decreased from 7.93 +/- 0.93 to 5.09 +/- 0.33 ml/min . kg (p less than 0.05), whereas lidocaine intrinsic clearance remained unchanged; bioavailability increased from 0.601 +/- 0.076 to 1, resulting in an abrupt reduction of oral clearance from 18.01 +/- 4.90 to 5.09 +/- 0.33 ml/min . kg (p less than 0.05). In group 2, ICG systemic clearance decreased slightly from 3.90 +/- 0.39 to 2.28 +/- 0.16 ml/min . kg (p less than 0.01) and ICG intrinsic clearance was not modified; lidocaine systemic and intrinsic clearance remained unchanged; and bioavailability increased from 0.779 +/- 0.229 to 1, resulting in a decrease of oral clearance from 7.68 +/- 1.65 to 4.23 +/- 0.37 ml/min X kg (p less than 0.05). The aminopyrine breath test was not affected by surgery in either group. We conclude that reduction of hepatic blood flow after portacaval shunt has only minimal effects on drug disposition in patients with severe liver disease, but results in a notable reduction in the clearance of high-extraction drugs in cirrhotics with mild liver disease.     

Evaluation of liver functional reserve by combining D-sorbitol clearance rate and CT measured liver volume

AIM: Our research attempted to evaluate the overall functional reserve of cirrhotic liver by combination of hepatic functional blood flow, liver volume, and ChildPugh′s classification, and to discuss its value of clinical application.METHODS: Ninety two patients with portal hypertension due to hepatic cirrhosis were investigated. All had a historyof haematemesis and hematochezia, esophageal and gastric fundus varices, splenomegaly and hypersplenia.A 2-year follow-up was routinely performed and no one was lost. Twenty two healthy volunteers were used as control group. Blood and urine samples were collected 4times before and after intravenous D-sorbitol infusion.The hepatic clearance (CLH) of D-sorbitol was then calculated according to enzymatic spectrophotometric method while the total blood flow (QToTAL) and intrahepatic shunt (RINs) were detected by multicolor Doppler ultrasound, and the liver volume was measured by spiral CT. Data were estimated by t-test, variance calculation and chi-squared test. The relationships between all these parameters and different groups were investigated according to Child-Pugh classification and postoperative complications respectively.RESULTS: Steady blood concentration was achieved 120 mins after D-sorbitol intravenous infusion, which was (0.358±0.064) mmoⅠ@L-1 in cirrhotic group and (0.189±0.05)mmol@L-1 in control group (P＜0.01). CLH=(812.7±112.4) ml@min-1,QTOTAL=(1280.6±131.4) ml@min-1, and RINS=(36.54±10.65)%in cirrhotic group and CLH=(1248.3±210.5) ml.min-1, QTOTAL=(1362.4-±126.9) ml@min-1, and RINS=(8.37±3.32) % in control group (P＜0.01). The liver volume of cirrhotic group was 1057±249 cm3, 851±148 cm3 and 663±77 cm3 in Child A, B and C group respectively with significant difference (P＜0.001).The average volume of cirrhotic liver in Child B, C group was significantly reduced in comparison with that in control group (P＜0.001). The patient, whose liver volume decreased by 40 % with the CLH below 600 ml@min-1, would have a higher incidence of postoperative complications. There was no strict correspondent relationship between CLH, liver volume and Child-Pugh′s classification.CONCLUSION: The hepatic clearance of D-sorbitol, CT measured liver volume can be reliably used for the evaluation of hepatic functional blood flow and liver metabolic volume. Combined with the Child-Pugh′s classification, it could be very useful for further understanding the liver functional reserve, therefore help determine reasonable therapeutic plan, choose surgical procedures and operating time.     

Combined evaluation of total and functional liver plasma flows and intrahepatic shunting

A diagnostic protocol was studied, designed to evaluate the main parameters of liver circulation in man. A water solution ofd-sorbitol (S) and indocyanine green (ICG) was infused intravenously in six controls and nine cirrhotics. Steady-state renal and hepatic S clearances as well as hepatic ICG clearance were calculated. In controls the values (mean ±sd) of the independent measurements of S and ICG hepatic clearance were 978±107 and 519±142 ml/min, respectively, while in cirrhotic patients they were 554±238 and 231±90 ml/min. Owing to the kinetic properties of S, its hepatic clearance may be regarded as a measure of functional liver plasma flow (FLPF). The total liver plasma flow (TLPF) values (mean±sd), calculated according to Fick's principle, were 1091±157 ml/min (S method) and 1033±153 ml/min (ICG method) in controls, and 1251±554 and 1284±677 ml/min in cirrhotics. In controls, FLPF was found to be very close to TLPF. In cirrhotic patients the difference between TLPF and FLPF (ranging from 169 to 2093 ml/min when measured by S method) was considered as an approximate estimate of intrahepatic shunting. The procedure is safe and simple and may add a new dimension to the investigation of hepatic circulation.This work was supported in part by grants from the Ministero della Pubblica Istruzione.     

Balloon-occluded retrograde transvenous obliteration improves liver function in patients with cirrhosis and portal hypertension

BACKGROUND AND AIM: Balloon-occluded retrograde transvenous obliteration (B-RTO) is a novel therapeutic method for the treatment of large gastric fundal varices with spontaneous splenorenal shunt (SRS). However, the effects of B-RTO on liver function remain unknown. METHODS: Fourteen patients with portal hypertension and gastric varices with SRS were studied, consisting of four patients with acute bleeding, five with high-risk varices, and five with refractory portosystemic encephalopathy. Hepatic venous catheterization was performed to evaluate hepatic blood flow and liver function using the continuous indocyanine green (ICG) infusion method. To assess the metabolic activity of the hepatocyte, the intrinsic clearance of ICG was calculated. In all patients, endoscopic study was performed before and 1 week and 1 month after the B-RTO, and followed every 6 months thereafter. After baseline measurements, B-RTO was performed. Four weeks after the B-RTO, the same catheter measurements were repeated. RESULTS: The B-RTO was successful in all patients. Contrast-enhanced computed tomography showed complete obliteration of the SRS prior to the follow-up measurements. Endoscopic eradication of the fundal varices was obtained 6 months after B-RTO in all patients and encephalopathy was improved within 1 week after B-RTO. Following the B-RTO, hepatic blood flow (441 +/- 214 vs 668 +/- 299 mL/min, P < 0.0001) and the intrinsic clearance of ICG (233 +/- 123 vs 285 +/- 148 mL/min, P < 0.05) were significantly increased. Furthermore, intrahepatic resistance decreased after the B-RTO (P < 0.005). CONCLUSION: From short-term assessment, B-RTO increases hepatic blood flow and improves the metabolic activity of the liver in patients with portal hypertension.     

Functional hepatic flow in patients with liver cirrhosis

AIM: To evaluate hepatic reserve function by investigating the change of functional hepatic flow and total hepatic flow in cirrhotic patients with portal hypertension. METHODS: HPLC method was employed for the determination of concentration of D-sorbitol in human plasma and urine. The functional hepatic flow (FHF) and total hepatic flow (THF) were determined by means of modified hepatic clearance of D-sorbitol combined with duplex doppler color sonography in 20 patients with cirrhosis and 10 healthy volunteers. RESULTS: FHF, evaluated by means of the D-sorbitol clearance, was significantly reduced in patients with cirrhosis in comparison to controls (764.74+/-167.91 vs 1195.04+/-242.97 mL/min, P<0.01). While THF was significantly increased in patients with cirrhosis in comparison to controls (1605.23+/-279.99 vs 1256.12+/-198.34 mL/min, P<0.01). Portal blood flow and hepatic artery flow all were increased in cirrhosis compared to controls (P<0.05 and P<0.01). D-sorbitol total clearance was significantly reduced in cirrhosis compared to control (P<0.01), while D-sorbitol renal clearance was significantly increased in cirrhosis (P<0.05). In controls FHF was similar to THF (1195.05+/-242.97 vs 1256.12+/-198.34 mL/min, P=0.636), while FHF was significantly reduced compared with THF in cirrhosis (764.74+/-167.91 vs 1605.23+/-279.99 mL/min, P<0.01). CONCLUSION: Our method that combined modified hepatic clearance of D-sorbitol with duplex doppler color sonography is effective in the measurement of FHF and THF. FHF can be used to estimate hepatic reserve function.     

Effect of oral propranolol on splanchnic oxygen uptake and haemodynamics in patients with cirrhosis

In order to elucidate the effect of beta-adrenergic blockade on liver metabolism and haemodynamics, splanchnic oxygen uptake, hepatic removal of indocyanine green (ICG) and splanchnic and systemic haemodynamics were studied in 13 patients with cirrhosis before and 1.5-2 h after an oral dose of 80 mg propranolol. All patients underwent hepatic vein catheterization and had a primed continuous intravenous infusion of ICG. Azygos vein catheterization was performed in six patients. Splanchnic (hepatic-intestinal) oxygen uptake (median control 68 ml/min vs. beta-blockade 56 ml/min, P less than 0.01), azygos venous oxygen saturation (76 vs. 67%, P less than 0.05), ICG clearance (263 vs. 226 ml/min, P less than 0.01), wedged-to-free hepatic vein pressure (16 vs. 13.5 mm Hg, P less than 0.01), hepatic blood flow (1.18 vs. 0.78 l/min, P less than 0.01), cardiac index (3.42 vs. 2.53 l/min . min 2, P less than 0.01), and heart rate (72 vs. 56 beats per min, P less than 0.01) decreased significantly after oral beta-blockade. The hepatic extraction ratio of ICG increased significantly (0.32 vs. 0.45, P less than 0.01), whereas estimated 'intrinsic' ICG clearance (289 vs. 300 ml/min, n.s.), arterial blood pressure, stroke volume, and systemic vascular resistance remained essentially unchanged. The results indicate that besides the well-known cardiovascular effects of propranolol, beta-adrenergic blockade may also reduce hepatic metabolic functions as evidenced by the significantly decreased splanchnic oxygen uptake. The raised hepatic extraction ratio of ICG may be caused by reduction in hepatic blood flow as well as in intrahepatic shunting.     

Effect of aging on liver functions-an experimental study in a perfused rat liver model

BACKGROUND: Aging is associated with marked changes in the physiology of many organs. Aging of the liver has been little studied and findings are inconclusive. The purpose of this work was to determine the effect of aging on transport and metabolic functions of the liver as assessed by extraction ratio of indocyanine green (ICG) and urea flux respectively. Bile flow was also recorded. As ICG is removed exclusively by the liver without bioconversion, its clearance reflects hepatic functional mass. METHODS: Livers from adult (3-month old) or old (24-month old) rats were perfused in a recirculating system for 90 min. At time 30 min, a bolus of 0.125 mg of indocyanine green was introduced in the perfusion buffer. At least every 10 minutes, the perfusion buffer was sampled for the measurements of ICG and urea. Bile flow was closely monitored throughout the experiment. RESULTS: Extraction ratio of ICG was increased in livers from old rats (9.49 +/- 2.84 vs 3.70 +/- 1.56% of ICG extracted), whereas urea flux was diminished (0.33 +/- 0.06 vs 1.33 +/- 0.65 micromol/min/% of ICG extracted) and bile flow was unchanged (4.03 +/- 1.02 vs 3.57 +/- 1.34 microl/min). CONCLUSIONS: Aging does not affect the different functions of the liver in the same way. It increases hepatocellular uptake function, but decreases the metabolic function of hepatocytes and does not change excretion function. These discrepancies are likely to be of some importance in the study of drug metabolism and action, and so we suggest that results should be corrected for ICG extraction.     

Verapamil has no effect on porto-hepatic pressure gradient, hepatic blood flow and elimination function of the liver in patients with liver cirrhosis

This study aimed to assess the effects of verapamil, a calcium-channel blocker, on porto-hepatic pressure gradient and on hepatic function as measured by the intrinsic hepatic clearance of indocyanine green (ICG) in patients with biopsy proven alcoholic cirrhosis. Hepatic venous pressures and hepatic extraction of ICG were measured before and 60 min after intravenous injection of 10 mg of verapamil in 19 consecutive patients. Hepatic blood flow and intrinsic hepatic clearance of ICG were calculated in the 10 patients whose hepatic extraction fraction was higher than 10%. No significant difference was observed when comparing porto-hepatic pressure gradient (17.72 +/- 4.79 vs. 17.77 +/- 4.43 mmHg), hepatic blood flow (13.47 +/- 4.75 vs. 16.13 +/- 7.88 ml.min-1.kg-1) and intrinsic hepatic clearance of ICG (1.99 +/- 0.54 vs. 1.97 +/- 0.45 ml.min-1.kg-1) before and after verapamil injection. We conclude that verapamil has no beneficial effect in patients with alcoholic cirrhosis.     

Single photon emission computed tomography to determine effective hepatic blood flow and intrahepatic shunting

The noninvasive determination of effective hepatic blood flow, intrahepatic shunted blood flow, intrahepatic shunt index, and total hepatic blood flow was investigated by using the sequential single photon emission computed tomography. This method was performed for a period of 10 minutes following an intravenous injection of ^99mTc-(Sn)-N-pyridoxyl-5-methyltryptophan and a venous blood sampling. This study comprised 8 healthy volunteers, 16 patients with chronic hepatitis, and 33 patients with liver cirrhosis. The intrahepatic shunt index measured with this method coincided with the intrahepatic shunt index determined by catheterization, indicating the high reliability of this procedure. The effective hepatic blood flow in patients with liver cirrhosis was significantly lower than that in the healthy controls and the chronic hepatitis group. The intrahepatic shunted blood flow was significantly higher in patients with liver cirrhosis compared with the flow in healthy controls. The intrahepatic shunt index was also significantly higher in patients with liver cirrhosis compared with the index of healthy controls and those with chronic hepatitis. No substantial differences were noted in the total hepatic blood flow among the three groups. The effective hepatic blood flow, the intrahepatic shunted blood flow, and the intrahepatic shunt index, correlated with the serum albumin concentration, the serum cholinesterase level, and the plasma indocyanine green attenuation rate. From these results, it was concluded that the present procedure constitutes a reliable and effective method for the noninvasive determination of hepatic blood flows. Consequently, it will be of high clinical value for assessing the functional and the pathological alterations of the liver.     

Effects of ranitidine on plasma clearance of indocyanine green in patients with liver cirrhosis

The effects of ranitidine on plasma clearance of ICG were investigated in 68 cirrhotic patients (9 were positive for HBsAg, 33 were alcoholics and 26 had cryptogenic cirrhosis). The ICG clearance test was performed before and after ranitidine administration. In 31 patients treated with ranitidine (150 mg perorally), the plasma ICG clearance were 233.6 +/- 20.4 ml/min (mean +/- S.E.) and 239.2 +/- 20.5 ml/min before and after ranitidine, respectively. In the 37 treated with intravenous ranitidine 50 mg, the corresponding values were 205.4 +/- 17.7 ml/min and 206.4 +/- 17.9 ml/min. There was no significant change in the plasma clearance of ICG or the elimination rate constant after ranitidine administration. Even in patients with decompensated liver cirrhosis, no significant change was demonstrated in the plasma ICG clearance after ranitidine. These results led to the conclusions that ranitidine does not reduce the hepatic blood flow and that it is a safe and useful drug for the treatment of gastrointestinal tract bleeding in patients with liver cirrhosis.