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.

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.

Blood flow, volume, and transit time in the pulmonary microvasculature using laser-Doppler

1994 ◽  
Vol 76 (6) ◽  
pp. 2643-2650 ◽  
Author(s):  
T. S. Hakim ◽  
E. Gilbert ◽  
E. M. Camporesi
Keyword(s):  
Blood Flow ◽  
Blood Volume ◽  
Transit Time ◽  
Flow Rate ◽  
Venous Pressure ◽  
Laser Doppler ◽  
Flow Volume ◽  
Doppler Flowmetry ◽  
Blood Flow Volume ◽  
Wide Range

Capillary transit time is determined by the ratio of capillary volume to flow rate. Exercise-induced hypoxemia is thought to occur because of the short transit time of erythrocytes in capillaries. The effect of flow rate on capillary volume (recruitment vs. distension) is controversial. In a perfused left lower lobe preparation in canine lungs, we used laser-Doppler flowmetry (model ALF21R) to monitor changes in blood flow, volume, and transit time in the microvasculature near the subpleural surface. Changes in total flow, blood volume, and total transit time (tt) were also measured. The results showed that microvascular volume approached maximum when flow rate was at resting value (0.4 l/min) and pressure in the pulmonary artery was > 6 mmHg relative to the level of the capillaries. In contrast, the total blood volume increased gradually over a wide range of flow rates. When flow increased 4.2 times (from 155 to 650 ml/min), tt decreased from 7.32 to 3.53 s; meanwhile, microvascular flow increased from 6.0 to 12.7 units and microvascular transit time decreased from 3.14 to 1.81 units. The changes in microvascular volume and transit time were essentially independent of whether the venous pressure was higher or lower than alveolar pressure. At very high flow (6–10 times resting value), tt fell gradually to approximately 1 s. Direct monitoring of transit time with the laser-Doppler also revealed a gradual decline in microvascular transit time as flow rate increased from 2 to 10 times the normal flow. (ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Temperature Effects on Radiocolloid Uptake by the Isolated Rat Liver

1957 ◽  
Vol 189 (1) ◽  
pp. 24-30 ◽  
Author(s):  
Ralph W. Brauer ◽  
R. J. Holloway ◽  
George F. Leong
Keyword(s):  
Blood Flow ◽  
Rat Liver ◽  
Hepatic Blood Flow ◽  
Reaction Rate ◽  
Extraction Efficiency ◽  
Liver Blood Flow ◽  
Isolated Rat Liver ◽  
Isolated Rat ◽  
Unambiguous Interpretation

Effect of temperatures between 20° and 38°C on the relation between blood flow and CrPO4 colloid uptake by the isolated rat liver has been studied. The Q10 for the over-all reaction rate is substantially constant and equal to 1.92 over this range. Theoretical limitations prevent the unambiguous interpretation of this value as a measure of the Q10 of the basic uptake reaction. Hemodynamic data indicate that cooling affects liver blood flow and liver blood distribution primarily, but not exclusively, through increasing blood viscosity. Evidence pointing to possible vasorelaxation under these conditions is mentioned. The application of these results to measurements of liver blood flow in hypothermia in vivo is discussed and the required diagram relating hepatic blood flow with the product of CrPO4 extraction efficiency and hepatic blood flow for the rat is presented.

Autoregulation of cochlear blood flow in guinea pigs

1994 ◽  
Vol 266 (2) ◽  
pp. H458-H467 ◽  
Author(s):  
J. N. Brown ◽  
A. L. Nuttall
Keyword(s):  
Blood Flow ◽  
Guinea Pigs ◽  
Venous Pressure ◽  
Vena Cava ◽  
Systemic Blood Pressure ◽  
Vascular Effects ◽  
Cochlear Blood Flow ◽  
Pharmacological Agents ◽  
Posterior Portion ◽  
Wide Range

Autoregulation of blood flow in the inner ear following uncontrolled changes in systemic blood pressure (BP), which was induced by the application of pharmacological agents that cause local and/or systemic vascular effects, has been reported in previous studies. In the current study, carotid BP was systematically manipulated without drugs, while the resulting cochlear blood flow (CBF) changes were measured using a laser Doppler flowmeter (LDF). Anesthesized guinea pigs were used, and the probe of a LDF was held against the ventral-posterior portion of the surgically exposed cochlea. A mechanical occluder was placed around the descending aorta or the inferior vena cava. BP could be elevated or lowered over a wide range and was held stable during 2-min occlusions. The mean level (+/- SD) of regulation (% delta CBF/% delta BP) for BP changes less than +/- 35% of preocclusion baseline was 0.24 +/- 0.2 (or 0.18 +/- 0.2 if BP is corrected by subtracting central venous pressure). Significant regulation occurred for BP between 20 and 70 mmHg. A demonstration of the cochlear origin of the regulatory response was obtained by “pharmacological blockade” following topical application of the vasodilator, sodium nitroprusside, to the cochlea. In this condition, CBF changed in nearly direct proportion to BP.

The effect of normothermic cardiopulmonary bypass on hepatic blood flow in the dog

Perfusion ◽  
1986 ◽  
Vol 1 (4) ◽  
pp. 245-253 ◽  
Author(s):  
RT Mathie ◽  
JB Desai ◽  
KM Taylor
Keyword(s):  
Blood Flow ◽  
Cardiopulmonary Bypass ◽  
Vascular Resistance ◽  
Flow Rate ◽  
Hepatic Blood Flow ◽  
Liver Blood Flow ◽  
Relative Reduction ◽  
Blood Flows ◽  
Pump Flow ◽  
Pump Flow Rate

Hepatic blood flow was investigated in two groups of eight anaesthetized dogs during and after one hour of either pulsatile or non-pulsatile cardiopulmonary bypass (CPB). Mean perfusion pressure was maintained at 60 mmHg. Hepatic arterial (HA) and portal venous (PV) blood flows were measured using electromagnetic flow probes, and hepatic O 2 consumption determined. The results demonstrate that: (a) pulsatile CPB reduces peripheral vascular resistance during and after perfusion, and more effectively preserves pump flow rate and cardiac output than non-pulsatile CPB; (b) total liver blood flow is sustained more effectively by pulsatile CPB than by non-pulsatile CPB due to relative preservation of both HA and PV flows; (c) hepatic O2 consumption is only marginally better preserved during and after pulsatile CPB than with non-pulsatile perfusion. We conclude that: (a) pulsatile CPB tends to maintain hepatic blood flow through a relative reduction in HA vascular resistance and an improvement in PV flow produced passively by a greater pump flow rate; (b) pulsatile CPB less effectively benefits hepatic O2 consumption because of poor O2 uptake from the hepatic PV blood supply.

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.

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