Combined Hepatic Vein, Umbilicoportal Vein, and Superior Mesenteric Artery Catheterization in Portal Hypertension: Estimation of the Portal Fraction of Total Hepatic Blood Flow in Cirrhotic Patients

Hemodynamic data were obtained in 13 cirrhotic patients with severe portal hypertension, undergoing combined hepatic vein, umbilicoportal vein, and superior mesenteric artery catheterization. The relative clearance of indocyanine green, the portohepatic gradient (difference between the free portal venous pressure and the free hepatic venous pressure), and the estimated hepatic blood flow were measured. The portal fraction (PF) of total hepatic blood flow was calculated in all patients using indicator dilution curves obtained from the portal bifurcation, a right hepatic vein, and when possible a left hepatic vein (six cases) after injection of ⁵¹Cr-labeled red blood cells (⁵¹Cr RBC) into the superior mesenteric artery. Flows were overestimated because of loss of indicator through spontaneous portosystemic shunts; however, the ratio between hepatic and portal indicator dilution curves can be used to calculate the portal fraction of total hepatic blood flow since no extrahepatic shunts existed after the bifurcation of the portal vein (as shown on portography). In 10 patients, 15 series of curves were calculable and the PF varied between 30.1 and 100% (mean ± SE: 71.1 ± 6.2%). In the three other patients, only delayed activity from recirculation was detected from portal and hepatic vein samples and PF was 0%; in these three cases, portography and arteriography revealed spontaneous portacaval shunting with reverse and/or stagnant circulation in the portal vein. In the 13 patients, no correlation existed between PF and the relative clearance of indocyanine green or the portohepatic gradient, parameters generally used as indices of severity in cirrhosis. In 10 patients, no correlation was found between PF and the estimated hepatic blood flow.     

肝硬化患者肝脏门静脉血流与肝叶萎缩之间关系的研究

目的：探讨肝硬化患者肝脏右叶、左叶体积变化,检测肝硬化患者门静脉血流情况,分析二者之间的关系,以及门静脉血流与肝功能之间关系。方法：本研究纳入54例肝硬化患者和40例正常人,采用超声多普勒方法分析这些受试者的肝脏体积和门静脉主干及左右分支的内径、血流速、流量数据,并通过静脉血检测白蛋白、胆红素、胆碱酯酶水平等评估患者肝功能水平。结果：肝硬化组平均年龄46.3岁,男性32例,其中childA级患者16例,childB级患者27例,childC级患者11例;正常对照组平均年龄41．8岁,男性24例。肝硬化组患者右左肝叶之比明显低于正常对照组（p〈0．05）,门静脉内径和血流量明显高于正常对照组（p〈0．05）．随着child分级升高,门静脉血流量也明显升高。肝硬化组门静脉右支血流量明显低于左支血流量（p〈0．05）;此外肝硬化患者门静脉右支和左支血流量之比明显低于正常人群门静脉右左支之比（p〈0．05）;而且肝硬化患者门静脉右左支血流量之比与右左肝叶具有明显的相关性与右左肝叶之比具有明显的相关性（r=0．64,p〈0．05）。结论：评估肝硬化病人门静脉血流情况,对于判断肝脏病理变化程度,评价治疗效果,以及选择治疗方案方面都具有重要的临床价值     

Validation of ⁹⁹mTechnetium-labeled mebrofenin hepatic extraction method to quantify meal-induced splanchnic blood flow responses using a porcine model

The aim of this study was to evaluate the measurement of the total splanchnic blood flow (SBF) using a clinical diagnostic method based on Fick's principle and hepatic extraction of 99mTc-mebrofenin (99mTc-MBF) compared with a paraaminohippuric acid (pAH) dilution method in a porcine model. Another aim was to investigate whether enterohepatic cycling of 99mTc-MBF affected the SBF measurement. Five indwelling catheters were placed in each pig (n = 15) in the portal, mesenteric, and hepatic veins, as well as in the aorta and the vena cava. The SBF was measured using both methods. The portal blood flow; the intestinal and hepatic oxygen uptake; the net fluxes of oxygen, lactate, and glucose; and the extraction fraction (EF) of 99mTc-MBF were measured before and for 70 min after feeding. The mean baseline SBF was 2,961 ml/min vs. 2,762 ml/min measured by pAH and 99mTc-MBF, respectively, and increased significantly to 3,977 ml/min and 3,981 ml/min postprandially. The hepatic EF of 99mTc-MBF decreased from 40% at the start of the investigation to 16% 70 min after feeding. The arterial-portal difference in 99mTc-MBF concentration was 0.21% (P = 0.48), indicating no intestinal extraction or metabolism. The clinical method for measuring the SBF based on hepatic 99mTc-MBF extraction is robust compared with the indicator dilution method, despite the decrease seen in hepatic extraction of 99mTc-MBF. Because there was no difference in the content of 99mTc-MBF between the arterial and portal vein plasma, the SBF can be calculated from an arterial and a hepatic vein sample.     

Splanchnic and systemic hemodynamic alterations in chronic, progressive portal hypertensive rats

Systemic and splanchnic hemodynamics were studied by using the radioactive microsphere technique, in rats in which a chronic and progressive portal or intrahepatic hypertension was produced by the placement of a nonconstricting, well fitted ligature around the portal or suprahepatic vein when the rat weighted about 100 g. The hemodynamic measurements were performed 80-90 days after ligature placement. Suprahepatic ligated rats presented portal and intrahepatic hypertension, but nonportal-systemic shunts (PSS). The only hemodynamic disturbance observed was a decrease in renal blood flow. Portal ligated rats showed a wide range of PSS and were divided in two subgroups. The subgroups with high PSS rate (greater than 10%) showed increased cardiac output and plasma renin content, as well as decreased splanchnic blood flow, portal venous inflow, hepatic blood flow and renal blood flow. Low portal-systemic shunts subgroups showed decreased cardiac output while its distribution was similar to the control rats. There was no correlation between portal pressure and shunt rate. Low shunt groups, furthermore, showed increased levels of plasma renin concentration.     

Intraportal glucose infusion and pancreatic islet blood flow in anesthetized rats

The aim of the study was to evaluate whether a selective increase in portal vein blood glucose concentration can affect pancreatic islet blood flow. Anesthetized rats were infused (0.1 ml/min for 3 min) directly into the portal vein with saline, glucose, or 3-O-methylglucose. The infused dose of glucose (1 mg. kg body wt(-1). min(-1)) was chosen so that the systemic blood glucose concentration was unaffected. Intraportal infusion of D-glucose increased insulin release and islet blood flow; the osmotic control substance 3-O-methylglucose had no such effect. A bilateral vagotomy performed 20 min before the infusions potentiated the islet blood flow response and also induced an increase in whole pancreatic blood flow, whereas the insulin response was abolished. Administration of atropine to vagotomized animals did not change the blood flow responses to intraportal glucose infusions. When the vagotomy was combined with a denervation of the hepatic artery, there was no stimulation of islet blood flow or insulin release after intraportal glucose infusion. We conclude that a selective increase in portal vein blood glucose concentration may participate in the islet blood flow increase in response to hyperglycemia. This effect is probably mediated via periarterial nerves and not through the vagus nerve. Furthermore, this blood flow increase can be dissociated from changes in insulin release.     

克仑特罗对绵羊肝脏血液中IGF-Ⅰ、GH和胰岛素水平的影响

克仑特罗 (ｃｌｅｎｂｕｔｅｒｏｌ ,ＣＬ)为一种 β -肾上腺素能受体激动剂。自 80年代初发现 β -受体激动剂可促进机体生长并改变机体胴体组成以来 ,许多研究均显示 β -激动剂具促进脂肪动员、减少体脂沉积、增加氮素贮存和促进蛋白质合成等作用 ,进而调节机体的生长发育 ,因而 β -激动剂又被称为“营养分重分配剂” (Ｙａｎｇ＆ＭｃＥｌｌｉｇｏｔｔ ,1989;Ｃａｒｄｏｓｏ＆Ｓｔｏｃｋ ,1996;Ｓｍｉｔｈ ,1998)。然而机体内代谢水平在很大程度上受内分泌的调控。在对影响机体生长发育的内分泌研究中 ,越来越多的证据表明胰岛素样生长…     

Glucose absorption, hormonal release and hepatic metabolism after guar gum ingestion.

Six non-anaesthetized Large White pigs (mean body weight 59 +/- 1.7 kg) were fitted with permanent catheters in the portal vein, the brachiocephalic artery and the right hepatic vein and with electromagnetic flow probes around the portal vein and the hepatic artery. The animals were provided a basal none-fibre diet (diet A) alone or together with 6% guar gum (diet B) or 15% purified cellulose (diet C). The diets were given for 1 week and according to a replicated 3 x 3 latin-square design. On the last day of each adaptation period test meals of 800 g were given prior to blood sampling. The sampling was continued for 8 h. Guar gum strongly reduced the glucose absorption as well as the insulin, gastric inhibitory polypeptide (GIP) and insulin-like growth factor-1 (IGF-1) production. However, the reduction in peripheral blood insulin levels caused by guar gum was not associated with a change in hepatic insulin extraction. IGF-1 appeared to be strongly produced by the gut. The liver had a net uptake of the peptide. Ingestion of guar gum increased the hepatic extraction coefficient of gut produced IGF-1. Guar gum ingestion also appeared to decrease pancreatic glucagon secretion. Cellulose at the level consumed had very little effect on the parameters considered. It is suggested that the modulation of intestinal mechanisms by guar gum was sufficient to mediate the latter internal metabolic effects.     

Active and passive liver microvascular responses from angiotensin, endothelin, norepinephrine, and vasopressin

Vasoconstrictor agents may induce a decrease in hepatic vascular volume passively, by decreasing distending pressure, or actively, by stimulating contractile elements of capacitance vessels. Hepatic venular resistance was estimated in anesthetized rabbits from hepatic venular pressure (P(mu hv); by servo-null micropipette), inferior vena cava pressure, and total hepatic blood flow (F(hv); by ultrasound flow probe). Changes in liver volume were estimated from measures of liver lobe thickness. Angiotensin (ANG) II, endothelin (ET)-1, norepinephrine (NE), and vasopressin (VP) were infused into the portal vein at a constant rate for 5 min. We conclude that ANG II and NE induced active constriction of hepatic capacitance vessels, because the liver lobe thickness decreased significantly even though P(mu hv) and portal venous distending pressure (P(pv)) increased. All four agents increased splanchnic and hepatic venous resistances in similar proportions. With VP, P(mu hv) and P(pv) decreased, but with ET-1, P(mu hv) and P(pv) increased. However, lobe thickness was not significantly changed by either drug during the infusion compared with the 2-min control period. Thus VP and ET-1 have only minor effects on hepatic capacitance vessels. ET-1, at 0.04 microg. min(-1). kg body wt(-1), caused an increase in systemic arterial blood pressure, but erythrocyte movement through the sinusoids in some animals stopped.     

Effects of hepatic blood flow on hepatic ethanol kinetics measured in cats and predicted from the parallel tube model

In cats anesthetized with pentobarbital, a long-circuit technique was used to measure hepatic blood flow while portal flow was varied from 0 to 300% of normal in random steps. Arterial, portal, and hepatic venous blood samples were analyzed for ethanol concentrations during continuous infusion of ethanol (20 mumol/(min.kg body weight) into the reservoir. Measured values for logarithmic mean sinusoidal ethanol concentration, hepatic venous ethanol concentration, hepatic ethanol uptake, and ethanol extraction were compared with the values predicted by the parallel tube model for hepatic uptake of substrates using Vmax and Km determined in each cat at the start of the experiment. Measured and predicted values were very similar at all blood flows above 65% control, but statistical regression analysis indicated a small but highly significant deviation of the measured values from the predicted values. At low flows, measured values of logarithmic mean sinusoidal and hepatic venous concentrations markedly exceeded the predicted values in most cats. The results indicate that the parallel tube model, which assumes all sinusoids are identical and equally perfused, provides a useful approximation for the effects of hepatic blood flow on hepatic ethanol kinetics except at low flows. However, there appears to be a significant degree of sinusoidal heterogeneity that results in a better fit to the distributed model. Our previously reported data for hepatic galactose uptake followed a similar pattern when reanalyzed in this more rigorous way.     

A portal-arterial glucose concentration gradient as a signal for an insulin-dependent net glucose uptake in perfused rat liver

Since in the usual perfusion of isolated rat liver via the portal vein an insulin-dependent increase of hepatic glucose uptake could not be demonstrated, the possibility was considered that hepatic glucose uptake might not be a function of the absolute concentration of this substrate but of its concentration gradient between the portal vein and the hepatic artery. Therefore a new method was established for the simultaneous perfusion of isolated rat liver via both the hepatic artery (20-35% flow) and the portal vein (80-65% flow). When glucose was offered in a concentration gradient, 9.5 mM in the portal vein and 6 mM in the hepatic artery, insulin given via both vessels caused a shift from net glucose release to uptake. This insulin-dependent shift was not observed when glucose was offered without a gradient or with an inverse gradient, 6 mM in the portal vein and 9.5 mM in the hepatic artery. Using a portal-arterial glucose gradient as a signal the liver might be able to differentiate between endogenous and exogenous glucose.     

An integrative model of amino acid metabolism in the liver of the lactating dairy cow

The objective of this work was to construct a dynamic model of hepatic amino acid metabolism in the lactating dairy cow that could be parameterized using net flow data from in vivo experiments. The model considers 22 amino acids, ammonia, urea, and 13 energetic metabolites, and was parameterized using a steady-state balance model and two in vivo, net flow experiments conducted with mid-lactation dairy cows. Extracellular flows were derived directly from the observed data. An optimization routine was used to derive nine intracellular flows. The resulting dynamic model was found to be stable across a range of inputs suggesting that it can be perturbed and applied to other physiological states. Although nitrogen was generally in balance, leucine was in slight deficit compared to predicted needs for export protein synthesis, suggesting that an alternative source of leucine (e.g. peptides) was utilized. Simulations of varying glucagon concentrations indicated that an additional 5 mol/d of glucose could be synthesized at the reference substrate concentrations and blood flows. The increased glucose production was supported by increased removal from blood of lactate, glutamate, aspartate, alanine, asparagine, and glutamine. As glucose output increased, ketone body and acetate release increased while CO(2) release declined. The pattern of amino acids appearing in hepatic vein blood was affected by changes in amino acid concentration in portal vein blood, portal blood flow rate and glucagon concentration, with methionine and phenylalanine being the most affected of essential amino acids. Experimental evidence is insufficient to determine whether essential amino acids are affected by varying gluconeogenic demands.     

Diminished hyperaemic response of the hepatic artery to portal venous occlusion (the buffer response) in Asian hybrid minipigs: a comparison of the response to that observed in dogs

The hyperaemic response of the hepatic artery to portal vein occlusion (the buffer response) and the action of exogenous adenosine upon hepatic artery blood flow was studied in Asian hybrid minipigs as a potential alternative experimental model to that previously developed in dogs. Adenosine produced a dose-dependent hepatic artery vasodilatation, but of lesser extent than that observed in dogs. A greatly diminished buffer response was observed in the pigs compared to that seen in dogs, and could not be replicated consistently. The adenosine uptake inhibitor dipyridamole did not potentiate responses to adenosine or the buffer response. It is concluded that the minipig is an unsuitable alternative model for the study of the hepatic artery buffer response.Abbreviations bw body weight - DPD dipyridamole - GDV gastroduodenal vein - HA hepatic artery - PV portal vein - PVO portal venous occlusion - PVP portal venous pressure - SE standard error     

Effect of reinfusions of autologous blood on the systemic and portal circulation in acute blood loss in rats

The experiments on rats using the method of contact luminescent biomicroscopy coupled with the ultrasonic measurement of systemic blood pressure and blood flow velocity in the portal vein and hepatic artery have revealed that portal micro- and macrocirculation reflects the degree of efficacy of acute hemorrhage treatment with autoblood. Autoblood infusion in animals with compensatory type of posthemorrhagic period restored systemic blood pressure and blood flow velocity in the portal vein and hepatic artery, promoting the development of erythrocyte aggregation and local microcirculation disturbances in the central zone of hepatic functional elements.     

Effect of met-enkephalin and morphine on gastric secretion and blood flow

The effects of met-enkephalin and morphine on gastric acid and pepsin secretion and gastric mucosal and total blood flow were studied in anaesthetized dogs with an in vivo chambered secretion stomach preparation. It was found that both agents infused intraarterially caused an increase in histamine-induced acid and pepsin secretion and mucosal and total blood flow. The above responses were significantly blocked by naloxone and nalorphine. In the resting stomach both opiates did not induce secretory changes but they increased mucosal and total blood flow. Met-enkephalin and morphine were also effective after intravenous administration. Met-enkephalin but not morphine fails to stimulate acid secretion if given into the portal vein. The likely mechanism of action of opiates on gastric secretion is discussed and a hypothesis of existence of opiate receptors in the gastric wall is presented.     

Method for measuring hepatic uptake of oxygen or other blood-borne substances in situ.

A preparation is described by which hepatic arterial blood flow and portal venous blood flow can be accurately and continuously measured while simultaneously providing a method by which multiple blood samples can be taken from the hepatic artery, portal vein, and hepatic vein without disrupting hepatic hemodynamics or causing hemodilution. By this means hepatic uptake or release of blood-borne substances can be measured in situ and correlated with hemodynamic parameters. In 13 splenectomized cats, oxygen uptake by the denervated liver was 4.5 +/- 0.3 ml . min-1. 100 g-1 of tissue, representing 54% of total oxygen removed by the splanchnic bed. The hepatic hemodynamics determined by this method are similar to those reported by others in vivo and the metabolic state of the liver remained stable for at least 2 h during which an average of 29 blood samples were taken. Advantages of this preparation over other methods of obtaining similar data are discussed.     

The use of 8-phenyltheophylline as a competitive antagonist of adenosine and an inhibitor of the intrinsic regulatory mechanism of the hepatic artery

Reduction of portal blood flow results in compensatory vasodilation of the hepatic artery, the hepatic arterial buffer response. The hypothesis tested is that the regulation of the buffer response is mediated by adenosine, where the local concentration of adenosine in the region of the hepatic arterial resistance vessels is regulated by washout of adenosine into portal venules that are in intimate contact with hepatic arterioles. In anesthetized cats, portal flow was reduced to zero by complete occlusion of all arterial supply to the guts. The resultant dilation of the hepatic artery compensated for 23.9 +/- 4.9% of the decrease in portal flow. Dose-response curves were obtained for the effect of intraportal adenosine infusion on hepatic arterial conductance in doses that did not lead to recirculation and secondary effects on the hepatic artery via altered portal blood flow. The dose to produce one-half maximal response for adenosine is 0.19 mg X kg-1 X min-1 (intraportal) and the estimated maximal dilation is equivalent to an increase in hepatic arterial conductance to 245% of the basal (100%) level. The adenosine antagonist, 8-phenyltheophylline, produced dose-related competitive antagonism of the dilator response to infused adenosine (but not to isoproterenol) and a similar, parallel antagonism of the hepatic arterial buffer response. If supramaximal blocking doses were used, the hepatic artery showed massive and prolonged constriction with blood flow decreasing to zero. The data strongly support the hypothesis that intrinsic hepatic arterial buffer response is mediated entirely by local adenosine concentration.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of portal hypertension on splenic blood flow,intrasplenic extravasation and systemic blood pressure

We have previously shown that intrasplenic fluid extravasation is important in controlling blood volume. We proposed that, because the splenic vein flows in the portal vein, portal hypertension would increase splenic venous pressure and thus increase intrasplenic microvascular pressure and fluid extravasation. Given that the rat spleen has no capacity to store/release blood, intrasplenic fluid extravasation can be estimated by measuring the difference between splenic arterial inflow and venous outflow. In anesthetized rats, partial ligation of the portal vein rostral to the junction with the splenic vein caused portal venous pressure to rise from 4.5 +/- 0.5 to 12.0 +/- 0.9 mmHg (n = 6); there was no change in portal venous pressure downstream of the ligation, although blood flow in the liver fell. Splenic arterial flow did not change, but the arteriovenous flow differential increased from 0.8 +/- 0.3 to 1.2 +/- 0.1 ml/min (n = 6), and splenic venous hematocrit rose. Mean arterial pressure fell (101 +/- 5.5 to 95 +/- 4 mmHg). Splenic afferent nerve activity increased (5.6 +/- 0.9 to 16.2 +/- 0.7 spikes/s, n = 5). Contrary to our hypothesis, partial ligation of the portal vein caudal to the junction with the splenic vein (same increase in portal venous pressure but no increase in splenic venous pressure) also caused the splenic arteriovenous flow differential to increase (0.6 +/- 0.1 to 1.0 +/- 0.2 ml/min; n = 8). The increase in intrasplenic fluid efflux and the fall in mean arterial pressure after rostral portal vein ligation were abolished by splenic denervation. We propose there to be an intestinal/hepatic/splenic reflex pathway, through which is mediated the changes in intrasplenic extravasation and systemic blood pressure observed during portal hypertension.     

Involvement of the liver in the regulation of tryptophan availability. Possible role in the responses of liver and brain to starvation

The concentrations of free and total (free plus albumin bound) tryptophan were measured in plasma of blood taken from the portal vein, hepatic vein and abdominal aorta of male rats, fed, and starved for one and three days. Liver and brain tryptophan concentrations were measured in similar groups of rats.On starvation, there was an increase in arterial plasma free tryptophan concentration which took place peripherally and was paralleled by an increase in brain tryptophan. In both the fed and starved rats, the portal vein concentrations of free tryptophan were high and as the blood flowed through the liver they were reduced to relatively low levels not directly related to the arterial values. All these changes were due to alterations in degree of binding of tryptophan to plasma albumin.The measurements of plasma total tryptophan concentrations showed that postabsorptively and during starvation there was a net uptake of tryptophan by the peripheral tissues (which included brain), but no overall fall in plasma concentration. At the same time, there was a net release from the liver, and to a lesser extent from the portal-drained tissues. The released tryptophan largely entered the albumin bound plasma pool. Accompanying the hepatic output was a fall in tryptophan concentration in the liver which was apparently caused by altered cell membrane transport.The results suggest (1) that the liver protects the brain from the high free tryptophan level in portal blood, (2) that the availability of tryptophan to the brain is maintained postabsorptively and during starvation by hepatic output into the albumin bound pool and (3) that this release of tryptophan from the liver and the fall in intracellular tryptophan concentration are initiated by altered membrane transport. The pattern of changes is consistent with a role for tryptophan in the mediation of changes in liver protein synthesis and gluconeogenesis and cerebral serotonin turnover on starvation.     

克伦特罗对绵羊肝脏氮、挥发性脂肪酸和葡萄糖流量的影响

目的 :探讨克伦特罗 (CL)影响机体物质代谢的有关肝脏机制。方法 :利用多血管导管技术在 4只绵羊上测定CL (0 .8mg kgbw)对其肝脏氮、挥发性脂肪酸 (VFA)和葡萄糖流量的影响。结果 :CL处理期绵羊血中尿素氮昼夜流量始终低于对照期 ,肝静脉及门静脉处尿素氮平均水平分别下降 16 .86 % (P <0 .0 1) ,15 .5 1% (P <0 .0 1)。CL使肝静脉多肽水平下降 ,其平均流量下降 38.71% (P <0 .0 1) ,而门静脉处多肽流量变化不明显。CL还使门静脉处VFA流量有较大幅度的提高 ,其中乙酸平均流量增加 19.49% (P <0 .0 1) ,而肝静脉处VFA的昼夜水平变化不明显。此外 ,CL可使肝静脉中葡萄糖流量有较大幅度的提高 ,其葡萄糖平均流量上升 2 5 .96 % (P <0 .0 1)。门静脉血中葡萄糖循环水平也相应提高。结论 :CL可通过增加对肝脏氮的储留 ,促进肝脏对VFA的吸收和利用及提高肝脏中葡萄糖的异生从而促进机体的物质代谢     

Perfusion-limited effects of plasma drug binding on hepatic drug extraction

The hepatic elimination of phenytoin has been studied in the isolated rat liver perfused at constant flow with Krebs solution alone and in the presence of albumin. At an albumin concentration of 0.5 g/dl, 46.6% of the phenytoin was bound in the perfusate and the comparable value at 5.0 g/dl was 87.4%. The increase in binding resulted in a reduction in the hepatic extraction ratio from 0.67 in Krebs to 0.54 and 0.28 at the two albumin concentrations, respectively. Analysis of this data together with that from the literature on propranolol and warfarin indicated that they were consistent with the perfusion-limited model of hepatic clearance. Accordingly, the general relationship between the extraction ratio and the free fraction of drug in the blood is hyperbolic with the precise shape being determined by the ratio of the clearance of the drug from liver water to the hepatic blood flow rate.