Recovery of liver function in partially hepatectomized rats evaluated by aminopyrine demethylation capacity

Aminopyrine demethylation was investigated in rats after a 70% hepatectomy to assess possible parallelism between the recovery of mass and function. Tests were performed by analyzing 14CO2 exhalation from 0.1 microCi per 100 gm of body weight of [dimethylamine-14C]aminopyrine given intraperitoneally with incremental doses of unlabeled drug. Early after 70% hepatectomy, Vmax was reduced by 52%. This discordance between mass and function was not due to extrahepatic aminopyrine demethylation, since liver exclusion reduced demethylation of aminopyrine to nearly nil. Whether it results from increased liver blood flow in the remnant liver is less clear: portacaval anastomosis provoked an identical fall in Vmax and liver blood flow, but aortal-portal fistula which increased liver blood flow by 70% did not modify Vmax. The early increase in Vmax could be related to a "hepatotrophic" factor of splanchnic origin which increased after partial hepatectomy and decreased after portacaval shunt. After the early period, Vmax, expressed per gram of actual liver weight, returned to control range. Throughout regeneration (4 to 144 hr), no modification was observed in Km nor in cytochrome P-450 concentration. Enzymatic induction with phenobarbital increased the demethylation capacity more than liver weight in intact and regenerating liver. Except for the first hours after partial hepatectomy or after enzymatic induction, the aminopyrine demethylation capacity directly correlated with liver mass and may be useful in evaluating liver regeneration in vivo.     

Effects of end-to-side portacaval shunt and distal splenorenal shunt on systemic and pulmonary haemodynamics in patients with cirrhosis

BACKGROUND: Patients with cirrhosis exhibit splanchnic, peripheral and pulmonary vasodilation, which are thought to play a role in increasing portal pressure, promoting sodium retention and determining arterial hypoxaemia. The present study investigated whether these abnormalities are influenced by portal hypertension or by portal systemic shunting. METHODS: Sixty-one patients with cirrhosis who had haemodynamic measurements before and after end-to-side portacaval shunt (n = 30) or distal splenorenal shunt (n = 31) were evaluated. RESULTS: End-to-side portacaval shunts were more effective than distal splenorenal shunts in decompressing the portal system (portocaval pressure gradient 3.2 +/- 2.5 vs splenocaval gradient 6.5 +/- 3.2 mmHg, P < 0.0001), because of a greater shunt blood flow (33 +/- 12 vs 21 +/- 12 mL/min per kg, P < 0.005). Azygos blood flow and hepatic blood flow decreased significantly after both surgical shunts. However, end-to-side portacaval shunts caused a greater decrease in peripheral resistance than distal splenorenal shunts (-23 +/- 18 vs -11+/- 27%, P < 0.05). Mean arterial pressure and pulmonary vascular resistance were significantly reduced after an end-to-side portacaval shunt (-7 +/- 10%, P < 0.001 and -14 +/- 33%, P < 0.004, respectively), but not after splenorenal shunt. CONCLUSIONS: These results show that end-to-side portacaval shunts, despite normalizing portal pressure, worsen the peripheral and pulmonary vasodilatation. The splenorenal shunt that maintained a higher portal pressure, caused less peripheral vasodilatation and did not enhance pulmonary vasodilatation. These findings suggest that portal systemic shunting is more important than increased portal pressure in determining peripheral vasodilatation in cirrhosis.     

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.     

Changes in hepatic blood flow after various types of portal shunt in the rat

The relationship between liver trophicity and the early (24 h) or late (14 days) modifications of the hepatic blood flow were studied in the rat after several types of portosystemic shunts (portacaval shunt, mesocaval shunt, portacaval transposition and arterialization of the portal vein after portacaval shunt). Twenty-four hrs after portacaval shunt, the total hepatic blood flow was decreased to 60 p. 100 of the initial value and remained so during the following days. Within a week, there was a liver atrophy with a decrease of the LW/BW to 60 p. 100 of the preoperative value. Fourteen days after operation, the hepatic blood flow per gram of liver was similar to that observed preoperatively. Whatever the type of shunt, there was a significant relationship between total hepatic blood flow and liver weight, 14 days after operation. Thus, after portal diversion, the quality of the blood perfusing the liver has little incidence upon the maintenance of liver trophicity. These results suggest that hemodynamic factors are more important than hormonal (pancreatic) factors in the constitution of liver atrophy after end-to-side portacaval shunt.     

Intrasplenic hepatocellular transplantation corrects hepatic encephalopathy in portacaval-shunted rats.

The aim of this work was to evaluate the effect of intrasplenic hepatocellular transplantation on hepatic encephalopathy in an experimental model of chronic liver failure induced by end-to-side portacaval shunt in the rat. Inbred male Wistar Furth rats were divided into three groups: rats subjected to portacaval shunt (n = 10), rats subjected to portacaval shunt and intrasplenic hepatocellular transplantation of 10(7) hepatocytes isolated from livers of syngeneic rats (n = 10) and sham-operated rats (n = 10). Behavior tests were performed in a blind fashion at 3 wk, at 2 mo and at 3 mo after surgery. Spontaneous activity and nose-poke exploration by individual rats were studied in automated open field boxes equipped with infrared cells. Each cell beam interruption was automatically recorded on a microcomputer and transformed into a score index (counts/hour). Plasma levels of amino acids, ammonia and total biliary acids were measured. Portacaval shunt rats showed reduced spontaneous activity and nose-poke exploration scores. Intrasplenic hepatocellular transplantation significantly increased spontaneous activity after 2 mo and improved nose-poke exploration after 3 wk. At 3 mo, spontaneous activity and nose-poke exploration in portacaval shunt/intrasplenic hepatocellular transplantation rats were not significantly different from those of sham rats. Increases in plasma ammonia levels after portacaval shunt were not corrected. Amino acid imbalance and bile acid concentration in plasma were partially corrected by intrasplenic hepatocellular transplantation. These data show that intrasplenic hepatocellular transplantation can correct the neurological symptoms of hepatic encephalopathy in an experimental model of chronic liver failure and suggest that intrasplenic hepatocellular transplantation might be of therapeutic interest in chronic liver failure.     

Effect of mesentericocaval shunt upon globulin levels in the rat

Rats develop hyperglucagonemia after end-to-side portacaval shunt and also after splenocaval shunt. In this study, animals with mesocaval shunt were shown not to develop hyperglobulinemia or increased titers of lipopolysaccharide antibodies. It is currently thought that the hyperglobulinemia of cirrhosis results from diversion of immunogens past the liver into the systemic circulation with stimulation of sites of globulin synthesis. Since all procedures result in development of immune complexes in the systemic circulation, an alternative hypothesis was sought. It is proposed that the liver may regulate antibody production by the spleen but that this mechanism only operates if splenic venous blood passes through the liver. Portacaval shunt and splenocaval shunt result in diversion of splenic venous blood past the liver and, consequently, failure of regulation, while after mesocaval shunt, splenic venous blood still enters the liver and thus the regulatory mechanism could operate.Financial support was received from the Staff Research Fund of the University of Cape Town, the Harry Crossley Fund, and the Mauerberger Bequest.     

The evolution of changes in quantitative liver function tests in a rat model of biliary cirrhosis: correlation with morphometric measurement of hepatocyte mass

The aim of this study was to determine the prognostic significance of functional changes in the liver during progression of cirrhosis. Liver function was quantitated weekly by the aminopyrine breath test (measuring microsomal function) and the galactose breath test (measuring cytosolic function) in rats made cirrhotic by bile duct ligation (n = 14) and in sham-surgery controls (n = 9). Nine rats died spontaneously of cirrhosis. Both the aminopyrine breath test and galactose breath test were sensitive (89%) predictors of death within 1 week, but the galactose breath test was more specific (83%). Morphometric measurements of livers from surviving cirrhotic animals and controls (n = 5 each) showed that mean hepatocyte mass was maintained in the cirrhotic livers [cirrhosis (17.0 +/- 2.0) vs. controls (13.9 +/- 0.9 gm)]. The galactose breath test was also maintained, whereas the aminopyrine breath test was significantly decreased in the surviving cirrhotics. The galactose breath test, but not the aminopyrine breath test, correlated with hepatocyte mass (r = 0.67). The aminopyrine breath test correlated with microsomal aminopyrine N-demethylase activity (r = 0.78). Serial use of quantitative liver tests allows prediction of time of death from cirrhosis in this model.     

Cholesterol homeostasis in the rat with a portacaval anastomosis.

Studies were undertaken to determine the effect of portacaval anastomosis on cholesterol homeostasis in rats fed sucrose/lard under conditions of normal body growth. Four to 6 weeks after portacaval shunt surgery, we found decreases in plasma cholesterol and triglyceride concentrations, total liver weight, and hepatic microsomal protein concentration. Measurements oof hepatic 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase (EC 1.1.1.34) activity showed decreases in specific activity and total liver activity in portacaval shunt rats, but the enzyme diurnal rhythm remained. Decreased reductase activity in shunted rats was not due to an altered Km for D-HMG-COA, nor was an enzyme inhibitor found in the livers of the portacaval shunt animals. Sterol balance measurements in rats with shunts showed a 22% decrease in whole body cholesterol synthesis rate compared to controls. These metabolic studies, coupled with postmortem data, showed diminished bile acid synthesis, unchanged fecal neutral steroid excretion, and decreased net tissue accumulation of cholesterol during growth. The decreased whole body cholesterol synthesis rate ultimately led to a diminished total carcass cholesterol concentration in the rats with shunts.     

Case report: Portal-systemic encephalopathy due to a congenital extrahepatic portosystemic shunt

We present a case of portal-systemic encephalopathy due to a congenital splenorenal shunt. A 69 year old woman was admitted to hospital because of recurrent episodes of disturbed consciousness. The present episode had begun 3 months prior to admission. Although the patient demonstrated mildly slurred speech, the remainder of her neurological examination was unremarkable. She showed no clinical signs of portal hypertension and her liver function, except for a serum hepaplastin test of 58% and an ICG retention rate of 28% at 15 min, was normal. Her serum ammonium level was 210 μg/dL. The venous phase of a superior mesenteric arteriogram revealed a splenorenal shunt and narrowing of the portal vein, which was 4 mm in diameter. The histological findings, demonstrated by a needle liver biopsy specimen, were consistent with mild fibrosis and lymphocytic infiltration. Following the diagnosis of a splenorenal shunt in the absence of liver cirrhosis, ligature of the shunt was performed with a splenectomy. The portal vein pressure after ligature of the shunt rose from 12.5 to 18.8 mmHg. This shunt was thought to be of congenital origin. The high preoperative serum ammonia concentration decreased to the normal range postoperatively and the serum hepaplastin test and ICG retention rate similarly improved postoperatively. A follow-up superior mesenteric arteriogram was performed during the venous phase, demonstrating resolution of the shunt and decreased portal vein narrowing. The patient has suffered no further episodes of disturbed consciousness postoperatively.     

Hepatocyte ultrastructure in rats with portacaval shunt

The principal reported morphological consequence of portacaval shunt in the rat is liver atrophy. The present study was designed to investigate ultrastructural changes in hepatocytes using electron microscopy morphometry. Two weeks following portacaval shunt, rat livers were fixed by perfusion and hepatocyte organelles from the two opposite zones of the acinus (zones 1 and 3) were quantified. Liver weight/body weight decreased by 50%, hepatocyte-specific volume decreased by 30% (28% in zone 1 and 35% in zone 3). Estimated sinusoidal space increased, and estimated number of hepatocytes decreased by 50%. Hepatocytes had a normal ultrastructure except for mitochondria. Smooth endoplasmic reticulum-specific surface area was reduced by 65% (zone 3), and rough endoplasmic reticulum surface density was increased in zone 1 only. Mitochondriaspecific volume was unchanged but decreased inner and outer membrane-specific surface area in zone 3 suggests in this zone a change in their conformation and possibly their number. Golgi-rich area surface density increased but not significantly. Hepatocyte loss and atrophy and rearrangement of organelles represent a new ultrastructural steady state following portacaval shunt that may help explain the new functional steady state.     

Amino acid imbalance following portal diversion in the rat. The relevance of nutrition and of hepatic function

End-to-end portacaval transposition has previously been shown to produce less hepatocellular dysfunction than end-to-side portacaval shunt in the rat. Liver weight is also significantly reduced after portacaval shunt compared to portacaval transposition and these differences are not abolished by pair-feeding. Histological evidence of CNS damage is also reduced in transposed rats compared to shunted animals. This study examines the amino acid and hormone changes in these models. The characteristic amino acid changes of chronic liver disease (decreased branched-chain and elevated aromatic amino acids) are reproduced in portacaval shunt rats, but not in portacaval transposition. The differences between these groups in the branched-chain amino acids, but not those in the aromatic amino acids, are reduced by pair-feeding. Insulin and glucagon are elevated to a similar extent in both groups. These findings add further support to a role for peripheral amino acid imbalance in the pathogenesis of portal-systemic encephalopathy. Normal liver function, maintained by replacement of portal inflow with systemic blood, appears to minimize both CNS damage and amino acid changes.     

Phosphate-activated glutaminase activity is enhanced in brain, intestine and kidneys of rats following portacaval anastomosis

AIM: To assess whether portacaval anastomosis (PCA) in rats affects the protein expression and/or activity of glutaminase in kidneys, intestines and in three brain areas of cortex, basal ganglia and cerebellum and to explain the neurological alterations found in hepatic en-cephalopathy (HE). METHODS: Sixteen male Wistar rats weighing 250-350 g were grouped into sham-operation control (n=8) or portacaval shunt (n=8). Twenty-eight days after the procedure, the animals were sacrificed. The duodenum, kidney and brain were removed, homogenised and mitochondria were isolated. Ammonia was measured in brain and blood. Phosphate-activated glutaminase (PAG) activity was determined by measuring ammonia production following incubation for one hour at 37℃with O-phthalaldehyde (OPA) and specific activity expressed in units per gram of protein (μkat/g of protein). Protein expression was measured by immunoblotting. RESULTS: Duodenal and kidney PAG activities together with protein content were significantly higher in PCA group than in control or sham-operated rats (duodenum PAG activity was 976.95±268.87μkat/g of protein in PCA rats vs 429.19±126.92.μkat/g of protein in sham-operated rats; kidneys PAG activity was 1259.18±228.79μkat/g protein in PCA rats vs 669.67±400.8μkat/g of protein in controls, P<0.05; duodenal protein content: 173% in PCA vs sham-operated rats; in kidneys the content of protein was 152% in PCA vs sham-operated rats). PAG activity and protein expression in PCA rats were higher in cortex and basal ganglia than those in sham-operated rats (cortex: 6646.6±1870.4μkat/g of protein vs 3573.8±2037.4μkat/g of protein in control rats, P<0.01; basal ganglia, PAG activity was 3657.3±1469.6μkat/g of protein in PCA rats vs 2271.2±384μkat/g of protein in sham operated rats, P<0.05; In the cerebellum, the PAG activity was 2471.6±701.4μkat/g of protein vs 1452.9±567.8μkat/g of protein in the PCA and sham rats, respectively, P<0.05; content of protein: cerebral cortex: 162%±40% vs 100%±26%, P< 0.009; and basal ganglia: 140%±39% vs 100%±14%, P<0.05; but not in cerebellum: 100%±25% vs 100%±16%,P=ns). CONCLUSION: Increased PAG activity in kidney and duodenum could contribute significantly to the hyperam-monaemia in PCA rats, animal model of encephalopathy. PAG is increased in non-synaptic mitochondria from the cortex and basal ganglia and could be implicated in the pathogenesis of hepatic encephalopathy. Therefore, PAG could be a possible target for the treatment of HE or liver dysfunction.     

Influences of exogenous intake and nitrogen balance on plasma and brain aromatic amino acid concentrations.

In an effort to determine the sum of the factors influencing the plasma and brain concentrations of aromatic amino acids in rats with liver disease, rats with end-to-side portacaval shunts and their sham-operated controls were placed on various oral and intravenous diets by the techniques of parenteral nutrition. In sham-operated animals with normal hepatic function, the source of amino acids and their composition appeared to play little role in the plasma and brain aromatic amino acids and a derivative of brain tyrosine, octopamine. After end-to-side portacaval shunt, however, plasma and brain concentrations of aromatic amino acids were responsive to exogenous intake in the presence of hepatic impairment. In a group of rats with end-to-side portacaval shunt and presumed hepatic impairment, graded increments of protein equivalent were given with isocaloric hypertonic dextrose by the techniques of parenteral nutrition. When the animals achieved positive nitrogen balance, there were decreased levels in plasma and brain of the aromatic amino acids, phenylalanine and tyrosine, and a derivative of tyrosine, octopamine. A clear statistical relationship between plasma and brain tryptophan and nitrogen balance was not observed. The results suggest that in animals with hepatic impairment secondary to end-to-side portacaval shunt both exogenous intake and the level of catabolism (nitrogen balance) influence plasma and brain aromatic amino acids.     

Liver glycogen after portacaval shunt in rats

Theories to explain the metabolic effects of portacaval shunt (PCS) have frequently failed to take into account the sequelae of PCS-induced anorexia. In this study PCS rats, followed up to 42 days postoperatively, had a lower food intake than ad libitum-fed (ALC) controls and also lost 10% body wt compared to a 20% gain of ALC rats. Liver weight was significantly reduced in PCS rats compared to ALC rats, pair-fed sham-operated (S) and pair-fed normal control (PFC) rats. However, liver glycogen was equally reduced in all animals with reduced food intake (PCS, S, and PFC rats) compared to ALC rats. Plasma glucose was significantly lower in PCS rats and PCS rats had markedly elevated plasma glucagon and lower plasma insulin concentrations than ALC rats, with the result that they had a low insulin: glucagon molar ratio of 1.3:1 compared to 10.2:1 in the ALC rats. The pair-fed control groups had intermediate I:G ratios and plasma glucose concentrations, thus an inverse relationship between mean plasma glucose and mean I:G ratio for each group was found, suggesting that the blood glucose concentration was the primary event determining the I:G ratio for each group.These controlled experiments indicate that hepatic atrophy after PCS appears to be directly related to the shunting of portal blood away from the liver, while reduced liver glycogen is related to decreased food intake. Reduction in total body weight, relative hypoglycemia, and elevated I:G ratios appear to be due to a combination of factors.     

Effect of portal arterialization on hepatic cytochrome P-450 in rats with portacaval shunt.

Fractional clearance of colloidal gold particles (k), liver weight and hepatic cytochrome P-450 were measured in rats with portacaval shunt and in rats with portacaval shunt plus arterialization of the hepatic stump of the portal vein. The effects of enzyme induction by phenobarbital was studied in both groups. Total arterialization of the liver provides a probably normal hepatic blood flow and seems to protect the liver from post-shunt atrophy. Nevertheless, in both arterialized and shunted rats, the cytochrome P-450 concentration was significantly lower than in controls. The same results were obtained after treatment by phenobarbital. These findings suggest that normal hepatic blood flow and oxygen supply are not the main determinant of a normal activity of the hepatic microsomal biotransformation system. Substances present in portal blood would probably be necessary in maintaining hepatic cytochrome P-450 level.     

Diet composition and surgical technique influence the postoperative recovery of portacaval shunted rats

In a series of experiments, rats were subjected to end-to-side portacaval shunts using either suture or nonsuture surgical procedures. Rats were maintained on cereal-based or purified diets in pellet form. All rats recovered preoperative body weights within the experimental periods; however, recovery of preoperative body weight was influenced by surgical technique and diet composition. Portacaval shunted rats fed a cereal-based diet required a longer period of time (14 days) to reattain preoperative body weights when compared to portacaval shunted rats fed a purified diet (7 days). Once preoperative body weight was recovered, growth rates of portacaval shunted rats were parallel to those of sham-operated controls. Rats with a suture-portacaval shunt appeared most sensitive to the feeding of a cereal-based diet. All portacaval shunted rats and sham controls fed a purified diet regained preoperative body weights within 7 days after surgery. Sham controls fed either a cereal-based or purified diet recovered preoperative body weights within an average of 4 days. Suture-portacaval shunted rats consuming a pellet form cereal-based diet showed a low feed efficiency which could be reversed by feeding a pellet form purified diet. Rats subjected to a nonsuture glue-portacaval shunt and fed a cereal-based diet showed 50% lower feed efficiencies than did glue-portacaval shunted rats fed a purified diet. Portacaval shunted rats decreased their consumption of cereal-based diets but not of purified diets postoperatively.(ABSTRACT TRUNCATED AT 250 WORDS)     

Improvement of quantitative testing of liver function in patients with chronic hepatitis C after installment of antiviral therapy

AIM: To investigate if and to what extent antiviral therapy influenced a broad panel of quantitative testing of liver function (QTLF). METHODS: Fifty patients with chronic hepatitis C were either treated with interferon (n=8), interferon/ribavirin (n=19) or peg-interferon/ribavirin (n=23). Quantitative testing of liver function, including aminopyrine breath test (ABT), galactose elimination capacity (GEC), sorbitol clearance (SCI) and indocyanine green clearance (ICG) was performed before and 3 mo after initiation of antiviral therapy. RESULTS: After 3 mo of antiviral treatment, 36 patients showed normal transaminases and were negative for HCV-RNA, 14 patients did not respond to therapy. ABT and GEC as parameters of microsomal and cytosolic liver function were reduced in all patients before therapy initiation and returned to normal values in the 36 therapy responders after 3 mo. Parameters of liver perfusion (SCI and ICG) were not affected by antiviral therapy. In the 14 non-responders, no changes in QTLF values were observed during the treatment period. CONCLUSION: ICG and SCI remained unaffected in patients with chronic hepatitis C, while ABT and GEC were significantly compromised. ABT and GEC normalized in responders to antiviral therapy. Early determination of ABT and GEC may differentiate responders from non-responders to antiviral treatment in hepatitis C.     

联合测定吲哚箐绿和D-山梨醇评价肝储备功能

目的 利用高效液相法(HPLC)测定正常肝脏和肝硬化肝脏的吲哚箐绿(ICG)肝固有代谢容量,并结合D-山梨醇无创测量肝功能性血流量、肝内分流率,全面评价肝储备功能。方法 制作大鼠肝硬化模型和肝脏隔离灌注模型,据HPLC法和Bergmeyer酶分光光度法分别测量ICG和D-山梨醇的药代动力学参数。结果 (1)HPLC证实ICG包括ICG原形(ICGg)和ICG降解产物(ICGdp)两种成分,保留时间分别为8.9min和24.2min,两种成分光谱相似,但体内代谢不同。(2)据ICGg计算的肝固有代谢容量(Q_(INT,I))在对照组和肝硬化组分别为(36.57±13.03)ml/min和(14.39±5.13)ml/min,肝硬化组Q_(INT,I)明显下降(t=7.08,P<0.01)。(3)肝功能性血流量(Q_(FUNC)),肝内分流率(Q_(IHS))在对照组和肝硬化组分别为:(34.06±5.12)ml/min和(17.54±7.02)ml/min,(9.9±1.4)％和(47.5±20.9)％,肝硬化组Q_(FUNC)显著下降(t=8.41,P<0.01),Q_(IHS)显著增加(t=8.35,P<0.01)。结论(1)HPLC法可避免ICGdp的干扰,优于传统的分光光度法,能用于肝固有代谢容量测定。(2)D-山梨醇肝清除率,是无创测定正常肝脏的总血流量,和肝硬化肝脏的肝功能性血流量、肝内分流率的实用可靠方法。(3)ICG与D-山梨醇联合使用,有助于全面评价肝脏功能状态。     

The effect of portal diversion upon function of the reticuloendothelial system and upon plasma fibronectin levels

A previous publication suggested that for 9 weeks after portal diversion in dogs, there were no changes in reticuloendothelial function assessed by measurement of t1/2 or phagocytic index of reticuloendothelial test lipid emulsion. The present study was conducted in rats over 18 weeks. It was observed that the phagocytic index decreased and the t1/2 lengthened at 18 weeks after either portacaval shunt or portacaval transposition and that plasma levels of fibronectin were elevated four- or five-fold after either form of diversion, whilst only being elevated two-fold after sham operation. There was an increase in portacaval shunt rats in liver tissue distribution of administered lipid emulsion when tested between 6 and 12 weeks post-operatively which then returned towards normal. The activity in portacaval transposition and sham-operated rats was unaltered. These studies suggest that the delay in clearance of administered particles in portacaval shunt and portacaval transposition rats is related to the portal diversion rather than to altered blood flow and thus the finding is of relevance in patients with cirrhosis who also have significant portacaval shunting.     

A comparison between antipyrine and aminopyrine blood clearances.

The purpose of this study was to investigate the relationship between two quantitative liver functions, that is, antipyrine blood clearance and aminopyrine blood clearance, in normal subjects and in patients with liver cirrhosis. The mean blood clearances of antipyrine and aminopyrine in cirrhotic patients (0.220 +/- 0.085 ml/min/kg and 1.13 +/- 0.56 ml/min/kg; n = 64) was 50% and 38% of that of normal subjects (0.440 +/- 0.110 ml/min/kg and 2.95 +/- 0.59 ml/min/kg; n = 11). While no significant correlation was demonstrated between these two values in normal subjects (n = 11, r = -0.107, p greater than 0.10), a strong positive correlation was observed between antipyrine and aminopyrine blood clearances in cirrhotic patients (n = 64, r = 0.846, p less than 0.001). These results suggest that both antipyrine and aminopyrine blood clearances may be valuable indicators for assessing the total hepatic functioning mass in cirrhotics.