Hepatic arterial perfusion regulates portal venous flow between hepatic sinusoids and intrahepatic shunts in the normal rat liver in vitro

Intrahepatic shunts regulate portal venous pressure during periods of acute portal hypertension when the transhepatic portal resistance is momentarily increased in the normal rat liver in vivo. Hepatic arterial inflow may also increase the transhepatic portal resistance and activate intrahepatic shunts. In the present study, the transhepatic portal resistance and the activity of intra-hepatic shunts were measured in vitro and the point of confluence between the hepatic artery and portal vein in the rat determined. Livers of male Sprague-Dawley rats were single-pass, dual-perfused in vitro. Total cessation or diversion of the hepatic arterial inflow to the portal venous vasculature, whilst maintaining total hepatic perfusate flow, decreased intrasinusoidal pressure, increased transhepatic portal venous resistance and opened the portal venous intrahepatic shunts in a manner similar to intraportal injection of 15-microm diameter microspheres. Injections of the microspheres into the hepatic arterial circulation increased hepatic arterial pressure dramatically, consistent with complete occlusion of the arterial vasculature. The intrahepatic shunts are located at a pre-sinusoidal level because no increases were detected in hepatic arterial pressure following intraportal injection of microspheres. The hepatic arterial vasculature, unlike the portal supply, does not possess a collateral shunt circulation and coalesces with the portal vein at an intrasinusoidal location     

Nitric oxide modulates acetylcholine-induced vasodilatation in the hepatic arterial vasculature of the dual-perfused rat liver.

The role of nitric oxide in the modulation of hepatic arterial vascular reactivity was investigated in an isolated dual-perfused rat liver preparation. Twelve male Wistar rats (200-250 g) were anaesthetized with sodium pentobarbitone (60 mg kg-1 i.p.). The livers were then excised and perfused in vitro through hepatic arterial and portal venous cannulae at constant flow rates. Concentration-dependent dose-response curves to acetylcholine (10(-8)-10(-5) M), sodium nitroprusside (10-6(-5) x 10(-4) M), and adenosine triphosphate (ATP) (10(-8)-10(-5) M) in the hepatic artery were constructed after the tone was raised by addition of methoxamine (3 micorM L(-1)). Acetylcholine-induced vasodilatation in the hepatic artery was significantly attenuated with inhibition of nitric oxide synthase by using NG-nitro-L-arginine methyl ester (30 microM), Emax = 51.7 +/- 2.8 vs. 32.5 +/- 3.1 mmHg, before vs. after NG-nitro-L-arginine methyl ester, respectively. ATP-induced hepatic arterial vasoconstriction which was significantly enhanced with L-NAME, Emax = 94.0 +/- 9.3 vs. 127.0 +/- 8.0 mmHg, before vs. after NG-nitro-L-arginine methyl ester, respectively. Sodium nitroprusside-induced hepatic arterial vasodilatation remained unchanged with NG-nitro-L-arginine methyl ester, Emax = 57.0 +/- 3.4 vs. 57.0 +/- 4.1, before vs. after NG-nitro-L-arginine methyl ester, respectively. The data from the present study suggest that acetylcholine-induced vasodilatation in the intrahepatic arterial vasculature of the rat liver is at least, in part, mediated by the release of nitric oxide. In addition, ATP-induced hepatic arterial vasoconstriction is also modulated by the release of nitric oxide (*P < 0.05, Student's paired t-test).     

Three-dimensional organization of the hepatic microvasculature in hereditary hemorrhagic telangiectasia

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant systemic fibrovascular dysplasia. Although hepatic vascular shunts are often observed in HHT, the responsible pathological mechanism is unknown. This issue was addressed by performing a 3-dimensional reconstruction study of the hepatic microvasculature of an HHT-involved liver in a 79-year-old woman. Clinical observation revealed high-output congestive heart failure and hepatic encephalopathy due to arteriovenous and portovenous shunts, respectively. Angiography revealed tortuous dilation of hepatic arterial branches and intrahepatic arteriovenous shunts. The 3-dimensional analysis of the autopsy liver revealed focal sinusoidal ectasia, arteriovenous shunts through abnormal direct communications between arterioles and ectatic sinusoids, and portovenous shunts due to frequent and large communications between portal veins and ectatic sinusoids. Type 1 HHT was suggested by the lack of endoglin immunoreactivity in the liver. The 3-dimensional reconstruction study of hepatic microvasculature was successful in identifying the pathological changes responsible for the intrahepatic shunts in HHT.     

Portal vein or hepatic vein? A curious aberrant vasculature in the liver with idiopathic portal hypertension

The existence of aberrant vasculatures has been described as one of the characteristic findings in the liver with idiopathic portal hypertension (IPH). In this paper, the morphological features and the genesis of aberrant vasculatures were studied on the basis of autopsy and biopsy materials of IPH and animal experiments. Aberrant vasculatures in IPH livers are characterized as thin-walled vessels located mainly adjacent to the portal tracts and at times in the hepatic lobules. Although some of them are morphologically very similar to hepatic vein branches, they are portal in nature. These aberrant vessels develop in order to compensate for portal circulatory insufficiency due to obliteration of portal vein branches, and play an important role in maintaining an adequate blood supply to the parenchyma. It is predicted that decrease of these intrahepatic collateral vessels is responsible for or related to parenchymal atrophy and deterioration of liver function in the advanced stage of this disease. We regard these vasculatures as characteristic of the intrahepatic portal venous obstruction, particularly with portal hypertension accompanied by increased portal blood flow.     

PORTAL VEIN OR HEPATIC VEIN ?

The existence of aberrant vasculatures has been described as one of the characteristic findings in the liver with idopathic portal hypertension (IPH). In this paper, the morphological features and the genesis of aberrant vasculatures were studied on the basis of autopsy and biopsy materials of IPH and animal experiments. Aberrant vasculatures in IPH livers are characterized as thin-walled vessels located mainly adjacent to the portal tracts and at times in the hepatic lobules. Although some of them are morphologically very similar to hepatic vein branches, they are portal in nature. These aberrant vessels develop in order to compensate for portal circulatory insufficiency due to obliteration of portal vein branches, and play an important role in maintaining an adequate blood supply to the parenchyma. It is predicted that decrease of these intrahepatic collateral vessels is responsible for or related to parenchymal atrophy and deterioration of liver function in the advanced stage of this disease. We regard these vasculatures as characteristic of the intrahepatic portal venous obstruction, particularly with portal hypertension accompanied by increased portal blood flow. ACTA PATHOL. JPN. 35 : 885–897, 1985.     

The clinical anatomy of congenital portosystemic venous shunts

Congenital portosystemic venous shunts are rare. Their gross anatomy has not been well defined. Four different varieties of congenital portosystemic venous shunts are described in six children seen during a 10-year period, focusing on the anatomy of the shunt as determined by imaging studies and surgery. A detailed review of the literature indicates that congenital portosystemic venous shunts are best classified as: extrahepatic or intrahepatic. Extrahepatic shunts may be further subdivided into portocaval shunts (type 1 end-to-side and type 2 side-to-side) and others. Intrahepatic shunts are due to an abnormal intrahepatic connection between the portal vein and hepatic vein/inferior vena cava or a persistent patent ductus venosus. Additional congenital anomalies, particularly cardiac malformations, may be associated with any type. Some congenital intrahepatic portosystemic venous shunts close spontaneously in infancy; all other congenital portosystemic venous shunts tend to remain patent. To a variable extent, depending largely on the volume and duration of the shunt, affected individuals are at risk of developing hepatic encephalopathy and/or an intrahepatic tumor. The key to understanding the pathogenesis of these shunts lies in the normal developmental mechanisms underlying the formation of the portal vein and inferior vena cava in the embryo.     

Liver Hemodynamics and Liver Function in Cats during Graded Hypoxic Hypoxemia

In 15 cats, anesthetized with chloralose and curarized, liver hernodynamics and liver function were followed during graded hypoxic hypoxemia. Hepatic arterial and intrahepatic portal venous conductance were not influenced by hypoxia, whereas severe hypoxemia increased gastrointestinal conductance. Total liver blood flow remained constant and hypoxemia was compensated for by an increase in hepatic extraction of oxygen approaching 100% Only when the hepatic venous PO₂ fell below 5–10 mmHg did hypoxemia decrease liver function. The results indicate that the sinusoidal perfusion is homogeneous.     

Control of hepatic and intestinal blood flow: effect of isovolaemic haemodilution on blood flow and oxygen uptake in the intact liver and intestines.

1. Limited isovolaemic haemodilution was produced in cats by addition of dextran 75-Ringer solution to an extracorporeal blood reservoir connected in series with the cat. Total hepatic venous outflow was neasured using a hepatic venous long-circuit and hepatic arterial flow was measured with an electromagnetic flow probe. Oxygen uptake was monitored in the guts and liver. Na-pentobarbitone anaesthesia was used. 2. Following reduction of the haematocrit (from 31 to 22) the oxygen uptake of the gut segment and liver were maintained. Gut conductance increased to 125% of control while the oxygen extraction ratio increased to only 109%. The hepatic arterial conductance did not change in spite of a greatly reduced (to 68%) oxygen delivery. Hepatic extraction increased to 140% of control. 3. The hepatic artery did not dilate to maintain constant oxygen supply to the liver thus confirming our previous observation that blood flow is not coupled to hepatic metabolism. 4. Oxygen extraction in the gut correlated well with changes in portal blood flow but not with changes in vascular conductance, arterial blood pressure or oxygen delivery. 5. The blood flow of the gut (vascular beds draining into the portal vein in the splenectomized preparation) was controlled in a manner that prevented changes in portal venous PO2 in spite of a reduction in oxygen content. Local PO2 and perhaps pH, are suggested as the factors controlling gut blood flow following haemodilution. 6. Changes in portal blood flow correlated with changes in portal vascular (intrahepatic) conductance such that increased portal flow produced an increased portal conductance thereby maintaining portal venous pressure constant.     

Influence of somatostatin on splanchnic haemodynamics in patients with liver cirrhosis

The influence of intravenous somatostatin infusion (7.6 micrograms/min) on systemic and splanchnic haemodynamics was examined in 10 patients with liver cirrhosis and portal hypertension. The hepatic vein catheter technique was employed and indocyanine green dye was injected to evaluate hepatic blood flow. Mean wedged hepatic venous pressure fell from 24.9 +/- 2.8 in the basal state to 21.4 +/- 3.2 mmHg (P less than 0.2) at 60 min of infusion and the mean arterial pressure decreased from 87 +/- 5 to 80 +/- 6 mmHg (P less than 0.05). The rate of indocyanine green dye disappearance decreased from 8.7 +/- 1.9 to 6.6 +/- 1.7%/min (P less than 0.001) during the infusion, indicating decreased hepatic blood flow. Arterial-hepatic venous oxygen differences rose from 69 +/- 11 to 78 +/- 11 ml/l. Blood glucose levels fell from 4.84 +/- 0.31 to 3.79 +/- 0.33 mmol/l at 60 min of infusion (P less than 0.005). It is concluded that a continuous infusion of somatostatin in patients with liver cirrhosis and portal hypertension causes a decreased hepatic blood flow with augmented hepatic oxygen extraction and a modest reduction in mean wedged hepatic venous pressure. In view of the magnitude of the observed haemodynamic changes the findings do not suggest an important role for somatostatin in the treatment of patients with bleeding oesophageal varices.     

Intrahepatic distribution of portal and hepatic arterial blood flows in anaesthetized cats and dogs and the effects of portal occlusion, raised venous pressure and histamine

1. Radioactive microspheres were used to determine the distribution of arterial and portal flows within the liver. (141)Ce-microspheres and (51)Cr-spheres were given to allow two determinations of flow distribution in each animal and experiments are described to establish the accuracy and validity of the method.2. Mean flow/g to any lobe or segment of a lobe in a group of animals was not markedly different from the mean flow/g to the whole liver, and in general the liver was homogeneously perfused with both portal and arterial blood. However, in any one liver, some areas received a relatively greater flow (up to 300%) and some a relatively smaller flow (down to 50%) at the time the microspheres were given. The gall bladder received a much smaller portal flow/g than the parenchyma but its arterial flow/g varied widely in different animals.3. If portal flow to an area of parenchyma was reduced by occlusion of a branch of the portal vein, this area received a significantly increased arterial flow.4. An increase in hepatic venous pressure did not cause a significant change in the intrahepatic distribution of either arterial or portal flows in cats.5. In dogs, infusions of histamine into the portal vein caused a redistribution of portal flow away from the free ends of the lobes towards the hilar ends but the distribution between lobes did not change and there was no redistribution of arterial flow.     

Effect of acid-base alterations on hepatic lactate utilization

1. The effect of acid-base changes on hepatic lactate utilization was investigated in anaesthetized, mechanically ventilated dogs.2. Portal vein flow and hepatic artery flow were measured with electromagnetic flowmeters, lactate concentration of portal vein, arterial and mixed hepatic venous blood was determined by an enzymatic technique, and hepatic lactate uptake was calculated using the Fick principle.3. Respiratory alkalosis (Delta pH 0.25 +/- 0.02) in four dogs resulted in a significant fall in total hepatic blood flow (-22 +/- 4%) and a significant rise in both arterial lactate concentration (2.18 +/- 0.32 m-mole/l.) and hepatic lactate utilization (3.9 +/- 1.2 mumole/min.kg).4. 0.6 M-Tris buffer infusion (Delta pH 0.21 +/- 0.02) in four dogs produced no significant changes in liver blood flow, arterial lactate concentration or hepatic lactate uptake.5. Respiratory acidosis (Delta pH -0.20 +/- 0.03) in six dogs and metabolic acidosis (Delta pH -0.20 +/- 0.02) in four dogs produced no significant changes in liver blood flow, decreases in arterial lactate concentration of 0.38 +/- 0.09 m-mole/l. (P < 0.05) and 0.13 +/- 0.13 m-mole/l., respectively, and no significant changes in hepatic lactate uptake.6. A significant correlation (r = 0.63; P < 0.01) was found between hepatic lactate utilization and arterial lactate concentration during the hyperlactataemia associated with respiratory alkalosis.7. Hyperlactataemia induced in four dogs by infusion of buffered sodium lactate (Delta pH 0.05 +/- 0.01;% Delta liver blood flow 29 +/- 7%) was also significantly correlated with hepatic lactate utilization (r = 0.70; P < 0.01) and the slope of the regression was similar to that during respiratory alkalosis.8. These data suggest that the hyperlactataemia of alkalosis is not due to impaired hepatic utilization of lactate and that the principal determinant of hepatic lactate uptake during alkalosis or lactate infusion is blood lactate concentration, rather than liver blood flow or acid-base status.     

Quantitative analysis of hepatic macro‐ and microvascular alterations during cirrhogenesis in the rat

Cirrhosis represents the end‐stage of any persistent chronically active liver disease. It is characterized by the complete replacement of normal liver tissue by fibrosis, regenerative nodules, and complete fibrotic vascularized septa. The resulting angioarchitectural distortion contributes to an increasing intrahepatic vascular resistance, impeding liver perfusion and leading to portal hypertension. To date, knowledge on the dynamically evolving pathological changes of the hepatic vasculature during cirrhogenesis remains limited. More specifically, detailed anatomical data on the vascular adaptations during disease development is lacking. To address this need, we studied the 3D architecture of the hepatic vasculature during induction of cirrhogenesis in a rat model. Cirrhosis was chemically induced with thioacetamide (TAA). At predefined time points, the hepatic vasculature was fixed and visualized using a combination of vascular corrosion casting and deep tissue microscopy. Three‐dimensional reconstruction and data‐fitting enabled cirrhogenic features to extracted at multiple scales, portraying the impact of cirrhosis on the hepatic vasculature. At the macrolevel, we noticed that regenerative nodules severely compressed pliant venous vessels from 12 weeks of TAA intoxication onwards. Especially hepatic veins were highly affected by this compression, with collapsed vessel segments severely reducing perfusion capabilities. At the microlevel, we discovered zone‐specific sinusoidal degeneration, with sinusoids located near the surface being more affected than those in the middle of a liver lobe. Our data shed light on and quantify the evolving angioarchitecture during cirrhogenesis. These findings may prove helpful for future targeted invasive interventions.     

Biliary secretion in elasmobranchs. II. Hepatic uptake and biliary excretion of organic anions.

[35S]Bromosulfophthalein ([35C]BSP), [14C]sodium taurocholate ([14C]NaTC), AND 10 MG OF UNLABELED BSP.and of phenol-3,6-dibromophthalein disulfonate (DBSP) per kilogram body weight were injected in the caudal artery of free-swimming dogfish sharks (Squalus acanthias) and small skates (Raja erinacea). Twenty-four hours later, 85.8 +/- 15.7% of [35S]BSP was recovered in bile and liver in dogfish and 78.4 +/- 9.9% in skates. Similar results were obtained for [14C]NaTC. Unlabeled BSP or DBSP (10 mg/kg body wt) were also selectively excreted in bile over a 4-day period and at comparable rates in both species. More than 85% of [35S]BSP, BSP, and DBSP in bile was in unconjugated form. Selective hepatic clearance of BSP occurred despite nonselective binding to liver homogenates and very low concentrations of binding proteins in liver cytosol. Analysis of the organic anion plasma disappearance curves suggest that the clearance of anions into bile in elasmobranchs is delayed disproportionately relative to hepatic uptake. Albumin-BSP infusions did not prevent selective hepatic uptake of [35S]BSP, although biliary excretion was delayed further. These studies demonstrate that transport systems for biliary excretion of organic anions evolved prior to migration of marine life from the sea and relatively independently of intrahepatic conjugation and organic anion-binding proteins.     

Hepatic insulin and glucagon extraction after their augmented secretion in dogs

Effects of intravenous arginine and cholecystokinin-pancreozymin (CCK-PZ) infusion on hepatic extraction of insulin (EI) and glucagon (EGG) and also on hepatic glucose output (HGO) were studied in anesthetized dogs. Because insulin and glucagon exert antagonistic effects on HGO, insulin:glucagon (I/GG) molar ratios were determined in the portal vein and also in peripheral vessels. During the arginine-CCK-PZ infusion the amount of insulin and glucagon coming to the liver increased 12- and 15-fold, respectively. In contrast EI decreased significantly from a control value of 62 +/- 6% to a nadir of 22 +/- 13%. EGG (control value 19 +/- 9%), however, was unaffected by arginine-CCK-PZ. The absence of any alteration in EGG cannot be attributed to the molecular heterogeneity of the immunoreactive glucagon. HGO increased fourfold in response to the pancreatic stimulation, whereas portal I/GG decreased significantly from 8.2 +/- 0.9 to 5.0 +/- 0.7. The concurrent femoral arterial I/GG (control 3.7 +/- 1.0) and mesenteric venous I/GG (control 2.1 +/- 0.5) increased significantly. These observations indicate that portal, but not peripheral, I/GG measurements reflect hepatic events in anesthetized dogs, probably because of the different extraction patterns for insulin and glucagon.     

Mesocaval and distal splenorenal shunts: Effect on hepatic function,hepatic hemodynamics,and portal systemic encephalopathy

Summary The effect of the mesocaval interposition shunt (n=12) and the distal splenorenal shunt (n=9) on the wedged hepatic venous pressure, the estimated hepatic blood flow, quantitative hepatic function, and the rate of portal systemic encephalopathy was evaluated in 21 patients who had bled from esophageal varices. After mesocaval shunt the wedged hepatic venous pressure was significantly reduced by 42% (from 26±3 mm Hg to 15±5 mm Hg,P<0.001) compared to 16% only (from 25±3 mm Hg to 21±2 mm Hg,P<0.005) after distal splenorenal shunt. The estimated hepatic blood flow also decreased significantly after mesocaval shunt by 61% (from 1.45±0.46 l/min to 0.56±0.25 l/min,P<0.001) compared to 29% (from 1.29±0.32 l/min to 0.91±0.39 l/min,P<0.05) after distal splenorenal shunt. Despite significantly different influences of both types of shunt operations on wedged hepatic venous pressure and estimated hepatic blood flow (P<0.001), postoperative changes of hepatic function were comparable in both groups of patients. The galactose elimination capacity, the initial plasma disappearance rate of Bromsulphalein, and the plasma ratio of valine, leucine, and isoleucine to phenylalanine and tyrosine were reduced by 13%, 26%, and 29%, respectively, after mesocaval shunt, compared to 12%, 25%, and 17% after distal splenorenal shunt. Only two patients of the mesocaval shunt group with the largest decrease in estimated hepatic blood flow developed portal systemic encephalopathy postoperatively, and the distal splenorenal shunt patients with their minor hemodynamic sequelae remained free of portal systemic encephalopathy.Abbreviations AP Serum alkaline phosphatase - BSP Bromsulphalein - BSP-k_i Initial plasma disappearance rate constant of BSP - BSP-45 min Plasma retention of BSP 45 min after i.v. injection - C_a Concentration of ICG in arterial blood - C_hv Concentration of ICG in hepatic venous blood - ChE Serum cholinesterase - DSRS Distal splenorenal shunt - EHBF Estimated hepatic blood flow - E-ICG Hepatic extraction of ICG - FHVP Free hepatic venous pressure - GEC Galactose elimination capacity - GPT Serum glutamic pyruvic transaminase - HCT Hematocrit - ICG Indocyanine green - MCS Mesocaval shunt - MRUS Maximal rate of urea synthesis - NCT Number-connection test - PHG Portohepatic gradient - PSE Portal systemic encephalopathy - PT Prothrombin time - PVP Portal venous pressure - R Removal of ICG - V + L + I/P + T Molar ratio of valine + leucine + isoleucine/phenylalanine + tyrosine - WHVP Wedged hepatic venous pressure     

Splanchnic clearance of plasma vasopressin in the dog: evidence for prehepatic extraction

It is generally considered that the liver is primarily responsible for the extraction of vasopressin from the circulating blood by the splanchnic viscera. To investigate this matter further, measurements were made in the anesthetized dog of the concentrations of vasopressin in arterial, portal venous, and hepatic venous plasma, and of total splanchnic plasma flow and hepatic arterial plasma flow. The total splanchnic vasopressin extraction ratio was 12.9 +/- 1.0%. However, the concentration of vasopressin in portal venous plasma was consistently lower than in arterial plasma, and there was a substantial prehepatic extraction of vasopressin, averaging 10.5 +/- 0.8%. A quantitative evaluation of the contribution of the "prehepatic" viscera, i.e., viscera with venous drainage into the portal vein, is provided by the relevant clearances of vasopressin. The prehepatic and total splanchnic vasopressin clearances were 1.58 +/- 0.20 and 3.04 +/- 0.31 ml X min-1 X kg-1, respectively. Thus, the splanchnic viscera other than the liver were responsible for approximately half of the splanchnic clearance of vasopressin; the remainder could be attributed to the liver. Immunoreactive vasopressin was not found in the bile. In splenectomized dogs, in which venous blood was collected from the superior mesenteric vein, the vasopressin extraction ratio was 14.6 +/- 2.3%, suggesting that the prehepatic clearance of vasopressin occurs largely in the mesenteric bed. A more specific localization of the prehepatic clearance sites has not as yet been made.     

Angiopoietin-1 causes reversible degradation of the portal microcirculation in mice: implications for treatment of liver disease

In many different liver diseases, such as cirrhosis, degradation of the microcirculation, including obliteration of small portal or hepatic veins contributes to disease-associated portal hypertension. The present study demonstrates the importance of angiogenesis in the establishment of arteriovenous shunts and the accompanying changes to the venous bed. One aspect of angiogenesis involves the branching of new vessels from pre-existing ones, and the molecular mechanisms controlling it are complex and involve a coordinated effort between specific endothelial growth factors and their receptors, including the angiopoietins. We modulated the hepatic vasculature in mice by conditionally expressing angiopoietin-1 in hepatocytes. In mice exposed to angiopoietin-1 during development, arterial sprouting, enlarged arteries, marked loss of portal vein radicles, hepatic vein dilation, and suggestion of arteriovenous shunting were observed. Most importantly, these phenotypic changes were completely reversed within 14 days of turning off transgene expression. Expression of excess angiopoietin-1 beginning in adulthood did not fully recapitulate the phenotype, but did result in enlarged vessels. Our findings suggest that controlling excessive angiogenesis during liver disease may promote the restoration of the portal vein circuit and aid in the resolution of disease-associated portal hypertension.     

血吸虫病性门静脉高压症兔肝脏微血管构筑变化的研究

目的:探讨血吸虫病门静脉高压症时肝脏微血管构筑的变化及其可能在全身高动力循环状态中的作用。方法:采用腹部敷贴法感染血吸虫尾蚴建立血吸虫病性肝纤维化模型,经插管检测心输出量(CO)、平均动脉压(MAP)、心率(HR)和肝静脉嵌塞压(WHVP),按公式计算心脏指数(CI)、外周血管阻力(SVR);通过血管铸型方法观察肝脏微血管构筑。结果:与正常兔比较,血吸虫病兔CO、CI明显增高,MAP和SVR显著降低,WHVP升高,两组间HR差异无统计学意义。肝脏微血管铸型观察,血吸虫病时肝内微血管形态和比例严重失常,肝窦显著膨大,门静脉主干增粗,肝内形成广泛的小吻合支,其间以门静脉终末支与肝静脉终末支、门静脉小分支直接引流入肝静脉多见。结论:血吸虫病性门静脉高压症兔存在肝内门-体分流病理改变,可能是形成全身高动力循环状态并维持门静脉高压的一个重要环节。     

A comparative histological and morphometric study of vascular changes in idiopathic portal hypertension and alcoholic fibrosis/cirrhosis

AIM: To examine the pathological changes of hepatic arteries in idiopathic portal hypertension (IPH) which is characterized by the obliteration of the intrahepatic portal vein branches and presinusoidal portal hypertension. METHODS AND RESULTS: Liver specimens (biopsied or surgically resected) from 20 patients with IPH, 20 patients with alcoholic fibrosis/cirrhosis (AF/C) and 20 histologically normal livers were used. The vascular lumina of arterial and venous vessels in portal tracts were morphometrically evaluated by an image analysis system. The ratio of portal venous luminal area to portal tract area (portal venous index) of IPH and that of AF/C were significantly reduced compared with normal liver. The portal venous index for IPH was significantly lower than that for AF/C. The ratio of hepatic arterial luminal area to portal tract area for AF/C was significantly higher than that in normal liver; however, that for IPH was similar to normal. The peribiliary vascular plexus was increased in AF/C but not in IPH. In AF/C, the number of mast cells and macrophages known to be the source of angiogenic substances was significantly increased in the portal tract compared with normal liver, while in IPH it was not increased. CONCLUSIONS: In AF/C, a reduction in portal venous lumen was associated with an increase of hepatic arterial lumen and of angiogenesis-related cells in portal tracts. However, such compensatory arterial changes were not evident in IPH, and this compensatory failure may be a feature of IPH.     

Comparison of the effects of hepatic nerve stimulation on arterial flow, distribution of arterial and portal flows and blood content in the livers of anaesthetized cats and dogs

1. The responses to hepatic nerve stimulation were studied in cats and dogs anaesthetized with sodium pentobarbitone. In three series of experiments, hepatic arterial flow was recorded by an electromagnetic flowmeter, intrahepatic distributions of arterial and portal flows were studied by radioactive microspheres, and hepatic volume responses were measured by a plethysmographic method.2. In cats, nerve stimulation produced a frequency-dependent decrease in hepatic arterial flow which was not maintained and autoregulatory escape occurred. In dogs, the initial decrease in arterial flow was similar but escape did not occur and the vasoconstriction was well maintained.3. In both cats and dogs, stimulation of the hepatic nerves did not cause a redistribution of either arterial or portal flows within the liver. Autoregulatory escape in the liver of the cat was not associated with an intrahepatic redistribution of arterial flow and is best interpreted as relaxation of the same vessels which were initially constricted, due to increased production of a vasodilator factor.4. Stimulation of the hepatic nerves caused a marked frequency-dependent decrease in hepatic volume which was well maintained and the responses were similar in cats and dogs. The quantitative importance of the liver as a blood reservoir is compared in relation to other vascular beds and the concept of the blood volume reserve is discussed.