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

1989 ◽  
Vol 67 (7) ◽  
pp. 728-733 ◽  
Author(s):  
C. V. Greenway
Keyword(s):  
Blood Flow ◽  
Hepatic Blood Flow ◽  
Ethanol Concentration ◽  
Hepatic Uptake ◽  
Distributed Model ◽  
Tube Model ◽  
Logarithmic Mean ◽  
Parallel Tube ◽  
Predicted Values ◽  
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 μmol/(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.Key words: liver circulation, ethanol metabolism, sinusoidal heterogeneity, distributed model for hepatic uptake.

Derecruitment in cat liver: extension of undistributed parallel tube model to effects of low hepatic blood flow on ethanol uptake

1989 ◽  
Vol 67 (10) ◽  
pp. 1225-1231 ◽  
Author(s):  
C. V. Greenway ◽  
L. Bass
Keyword(s):  
Blood Flow ◽  
Hepatic Blood Flow ◽  
Venous Pressure ◽  
Liver Blood Flow ◽  
Hepatic Uptake ◽  
Tube Model ◽  
Low Flows ◽  
Wide Range ◽  
Parallel Tube ◽  
Parallel Tube Model

Previous studies showed two deviations from the predictions of the undistributed parallel tube model for hepatic uptake of substrates: a small deviation at high flows and a large deviation at low flows. We have examined whether these deviations could be described by a single correction factor. In cats anesthetized with pentobarbital, a hepatic venous long-circuit technique with an extracorporeal reservoir was used to vary portal flow and hepatic venous pressure, and allow repeated sampling of arterial, portal, and hepatic venous blood without depletion of the cat's blood volume. Hepatic uptake of ethanol was measured over a wide range of blood flows and when intrahepatic pressure was increased at low flows. This uptake could be described by the parallel tube model with a correction for hepatic blood flow: [Formula: see text]. In 22 cats, [Formula: see text], k = 0.021 ± 0.0015 when flow (F) was in millilitres per minute per 100 g liver, and Km = 150 ± 20 μM when ĉ is the log mean sinusoidal concentration. (1 − e−kF) represents the proportion of sinusoids perfused and metabolically active. A dynamic interpretation of this proportion is related to intermittency (derecruitment) of sinusoidal flow. Half the sinusoids were perfused at a flow of 33 mL/(min∙100 g liver) and the liver was essentially completely perfused (> 95%) at the normal flow of 150 mL/(min∙100 g liver). Derecruitment was not changed by raising hepatic venous pressure, and it was not related to hepatic venous resistance.Key words: liver circulation, ethanol metabolism, liver blood flow, sinusoidal perfusion, portal pressure.

Effects of liver blood flow on hepatic uptake kinetics of galactose in anesthetized cats: parallel tube model

1987 ◽  
Vol 65 (6) ◽  
pp. 1193-1199 ◽  
Author(s):  
C. V. Greenway ◽  
F. J. Burczynski
Keyword(s):  
Blood Flow ◽  
Steady State ◽  
Hepatic Blood Flow ◽  
Venous Blood ◽  
Liver Blood Flow ◽  
Control Flow ◽  
Tube Model ◽  
Blood Flows ◽  
Parallel Tube ◽  
Parallel Tube Model

Hepatic galactose uptake in cats anesthetized with pentobarbital was determined during (i) steady-state infusions at several doses, (ii) rapidly increasing infusion rates at different blood flows, and (iii) prolonged infusion of a single dose at different blood flows. The hepatic venous long-circuit technique was used to allow frequent sampling of arterial, portal, and hepatic venous blood without depletion of the animal's blood volume and to allow measurement and alteration of total hepatic blood flow. Uptake was shown to follow Michaelis–Menten kinetics and was consistent with the "parallel tube model." The kinetic parameters Vmax and Kmax could be determined under steady-state and nonsteady-state conditions and were independent of hepatic blood flow over the range 60–150% of control flow. Mean Vmax was 80 μmol/(min∙100 g liver) and mean Km was 215 μM. Vmax declined by 50% when flow was reduced to half normal. It is concluded that the parallel tube model can be used to describe and predict hepatic galactose kinetics in anesthetized cats, although other models may fit the data equally well.

EXTRAHEPATIC METABOLISM OF RECOMBINANT TISSUE-TYPE PLASMINOGEN ACTIVATOR (tPA) IN DOGS

1987 ◽  
Author(s):  
K L L Fong ◽  
K E Boyle ◽  
C S Crysler ◽  
M S Landi ◽  
H E Griffin ◽  
...  
Keyword(s):  
Blood Flow ◽  
Hepatic Blood Flow ◽  
Systemic Circulation ◽  
Volume Of Distribution ◽  
Hepatic Uptake ◽  
Tissue Type ◽  
Systemic Clearance ◽  
Artery Ligation ◽  
Β Phase

Hepatic uptake has been proposed as the major mechanism of tPA clearance from systemic circulation. However, our recent studies demonstrated that tPA was rapidly Inactivated through complexation with protease Inhibitors in dog plasma In vitro, and that tPA-inhibitor complexes were present in plasma of dogs receiving tPA. Therefore, the present work was undertaken to differentiate hepatic from extrahepatlc clearance of tPA. Pharmacokinetics of tPA were determined in anesthetized beagle dogs with either Intact hepatic circulation or with Interrupted hepatic blood flow achieved by hepatic artery ligation and portal caval shunt.Recombinant two-chain tPA was administered as an Intravenous bolus dose (80 μg/kg) and plasma active tPA concentrations were measured using a modified and validated S-2251 chromogenlc assay. Following tPA administration to Intact dogs, plasma active tPA concentration declined blexponentlally with time with 84% of the active tPA eliminated during the α-phase. The t1/2's of the a and β-phase were 1.76 ± 0.74 and 6.23 ± 1.56 min, respectively. The systemic clearance was 25.98 ± 1.13 ml/min/kg and the volume of distribution at steady state (VDss) was 73.9 ± 15.1 ml/kg. Upon the elimination of hepatic blood flow, the systemic clearance was reduced by 54% while VDss was unaffected. The contribution of plasma Inactivation of tPA to the systemic clearance was estimated from in vitro Inactivation studies In 37°C plasma. Based on the pseudo first order Inactivation rate constants of 0.184 min-1 and 0.095 min-1 at Initial tPA concentrations of 25 and 250 IU/ml respectively, clearance rates from 5.02 to 9.2 ml/min/kg were calculated. These data suggest that (1) in Intact dogs, 46% of the tPA clearance occurs extrahepatlcally and (2) Inactivation of tPA in plasma accounts for a major portion of the extrahepatlc clearance.

Regulation of Gluconeogenesis and Ketogenesis during Rest and Exercise in Diabetic Subjects and Normal Men

1977 ◽  
Vol 53 (5) ◽  
pp. 411-418 ◽  
Author(s):  
L. Sestoft ◽  
J. Trap-Jensen ◽  
J. Lyngsøe ◽  
J. P. Clausen ◽  
J. J. Holst ◽  
...  
Keyword(s):  
Blood Flow ◽  
Hepatic Blood Flow ◽  
Ketone Bodies ◽  
Venous Blood ◽  
Hepatic Metabolism ◽  
Hepatic Uptake ◽  
Diabetic Group ◽  
Hepatic Venous Blood ◽  
Juvenile Diabetic ◽  
Normal Men

1. The splanchnic—hepatic metabolism of glucose, lactate, pyruvate, alanine, glycerol, non-esterified fatty acids (NEFA), ketone bodies and oxygen were investigated in five normal men and six juvenile diabetic subjects at rest and during exercise after an overnight fast. 2. A linear relationship was found between load (arterial concentration multiplied by hepatic blood flow) and splanchnic—hepatic uptake of lactate, pyruvate, glycerol and NEFA. The uptake of alanine was highly sensitive to load, but was also regulated by the concentration of hepatic venous glucagon. The uptake of pyruvate was high in exercising diabetic subjects, who had a high lactate/pyruvate concentration ratio in hepatic venous blood. 3. The rate of uptake of the total measured gluconeogenic precursors was significantly higher in the diabetic group at a given load. 4. The rate of ketogenesis was linearly related to the NEFA load in both groups; however, the rate of ketogenesis was twofold at a given load in the diabetic group. The highest rates of ketogenesis were found coincident with the highest concentrations of glucagon in hepatic venous blood. 5. The observed antiketogenic effect of exercise was due to a decreased load of NEFA, mainly caused by a decrease in the hepatic blood flow.

scholarly journals Tracer Disposition Kinetics in the Determination of Local Cerebral Blood Flow by a Venous Equilibrium Model, Tube Model, and Distributed Model

1987 ◽  
Vol 7 (4) ◽  
pp. 433-442 ◽  
Author(s):  
Y. Sawada ◽  
Y. Sugiyama ◽  
T. Iga ◽  
M. Hanano
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Equilibrium Model ◽  
Blood Concentration ◽  
Tissue Concentration ◽  
Distributed Model ◽  
Tube Model ◽  
Local Cerebral Blood Flow ◽  
Capillary Tube Model

Tracer distribution kinetics in the determination of local cerebral blood flow (LCBF) were examined by using three models, i.e., venous equilibrium, tube, and distributed models. The technique most commonly used for measuring LCBF is the tissue uptake method, which was first developed and applied by Kety (1951). The measurement of LCBF with the 14C-iodoantipyrine (IAP) method is calculated by using an equation derived by Kety based on the Fick's principle and a two-compartment model of blood–tissue exchange and tissue concentration at a single data point (Sakurada et al., 1978). The procedure, in which the tissue is to be in equilibrium with venous will be referred to as the tissue equilibration model. In this article, effects of the concentration gradient of tracer along the length of the capillary (tube model) and the transverse heterogeneity in the capillary transit time (distributed model) on the determination of LCBF were theoretically for the tissue sapling method. Similarities and differences among these models are explored. The rank order of the LCBF calculated by using arterial blood concentration time courses and the tissue concentration of tracer based on each model were tube model (model II) < distributed model (model III) < venous equilibrium model (model I). Data on 14C-IAP kinetics reported by Ohno et al. (1979) were employed. The LCBFs calculated based on model I were 45–260% larger than those in models II or III. To discriminate among three models, we propose to examine the effect of altering the venous infusion time of tracer on the apparent tissue-to-blood concentration ratio (Λapp). A range of the ratio of the predicted Λapp in models II or III to that in model I was from 0.6 to 1.3. In the future, there may be a need to determine which model should be used to calculate the LCBF based on this discriminator and to develop another discriminator by using multiple data points based on positron emission tomography.

Effect of fasting, epinephrine and glucose and insulin on hepatic uptake of nonesterified fatty acids

1960 ◽  
Vol 199 (3) ◽  
pp. 403-406 ◽  
Author(s):  
Melwyn B. Fine ◽  
Robert H. Williams
Keyword(s):  
Fatty Acids ◽  
Blood Flow ◽  
Hepatic Blood Flow ◽  
Operative Procedure ◽  
Hepatic Uptake ◽  
Hepatic Veins ◽  
Nonesterified Fatty Acids

Catheters placed in the portal and hepatic veins of dogs were maintained in position for 2–4 weeks, and experiments were performed in the unanesthetized state no less than 3 days after the operative procedure. Hepatic uptake of nonesterified fatty acids (NEFA) was determined from the portal-hepatic NEFA difference and the hepatic blood flow. Hepatic NEFA uptake was found to increase with fasting and after administration of epinephrine. It was found to decrease after the administration of glucose and insulin. It was concluded that these factors did not directly influence the liver to alter its NEFA uptake but that the liver responded primarily to the concentration of NEFA in the blood entering it.

scholarly journals Mechanism of increased hepatic uptake of unesterified fatty acid from serum of ethanol-treated rats

1976 ◽  
Vol 156 (1) ◽  
pp. 47-54 ◽  
Author(s):  
M A Abrams ◽  
C Cooper
Keyword(s):  
Blood Flow ◽  
Fatty Acid ◽  
Carbon Tetrachloride ◽  
Hepatic Blood Flow ◽  
General Circulation ◽  
Hepatic Uptake ◽  
Unesterified Fatty Acid ◽  
Moderate Dose ◽  
Dose Response Relationship ◽  
To Receive

Studies were made on the mechanism by which livers of ethanol-treated rats take up an increased fraction of the total flux of unesterified fatty acid in serum. It was found that ethanol (0.7g/kg) causes a twofold rise in the serum content of liver, and that this serum is in rapid equilibrium with the general circulation. The fractional hepatic uptake from serum of group of compounds with varying uptake mechanisms and metabolic fates was studied in control and ethanol-treated animals. All the compounds tested, including unesterified fatty acid, showed an enhanced uptake when ethanol was given. For one of the compounds, carbon tetrachloride, a dose/response relationship was established between the amount administered, the amount taken up by liver, and the amount metabolized. These findings were interpreted to mean that this dose of ethanol causes the liver to receive an increased flow of blood, and as a result all compounds present and capable of being taken by liver are taken up at an increased rate. Hepatic blood flow was measured by a technique that monitors the rate of clearance of a colloidal lipid emulsion. It was found that ethanol increased hepatic blood flow by about 60%. This effect of ethanol on hepatic blood flow provides an explanation for the fatty liver and the synergistic effect between an acute dose of ethanol and carbon tetrachloride. A hypothesis to explain why a moderate dose of ethanol causes triglyceride to accumulate in liver is presented.

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