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

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.

1989 ◽  
Vol 67 (10) ◽  
pp. 1225-1231 ◽  
Author(s):  
C. V. Greenway ◽  
L. Bass

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.


1989 ◽  
Vol 67 (7) ◽  
pp. 728-733 ◽  
Author(s):  
C. V. Greenway

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.


Perfusion ◽  
1986 ◽  
Vol 1 (4) ◽  
pp. 245-253 ◽  
Author(s):  
RT Mathie ◽  
JB Desai ◽  
KM Taylor

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.


1986 ◽  
Vol 64 (10) ◽  
pp. 1310-1315 ◽  
Author(s):  
F. J. Burczynski ◽  
C. V. Greenway

Experiments were carried out to determine the accuracy and validity of estimations of hepatic blood flow from clearance data during infusions of galactose in anesthetized cats. Clearance calculations were compared directly with the measured hepatic blood flows using a hepatic venous long-circuit technique. This technique allowed direct measurement and alteration of hepatic blood flow and collection of arterial and mixed hepatic venous blood samples without depletion of the animal's blood volume. It was found that infusions of galactose could not be used to estimate accurately hepatic blood flow. Infusion rate could not be used as an estimate of hepatic or splanchnic uptake owing to substantial and variable extrasplanchnic uptake. As a result, estimated hepatic flows allowing for incomplete extraction overestimated the true flow. On the other hand, extraction was less than 100%. This caused systemic galactose clearance to underestimate hepatic blood flow. These errors could cancel each other giving an apparently good estimate of hepatic flow from systemic galactose clearance. This agreement was fortuitous and occurred only at a specific dose and blood flow. We conclude that in the absence of independent measurements of both extrasplanchnic uptake and splanchnic extraction of galactose, systemic galactose clearance is not a reliable measure of hepatic blood flow in anesthetized cats. Until proved otherwise, it seems likely that this is also true in humans.


1957 ◽  
Vol 189 (1) ◽  
pp. 24-30 ◽  
Author(s):  
Ralph W. Brauer ◽  
R. J. Holloway ◽  
George F. Leong

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.


1978 ◽  
Vol 234 (5) ◽  
pp. H597-H607 ◽  
Author(s):  
D. F. Stowe ◽  
D. G. Mathey ◽  
W. Y. Moores ◽  
S. A. Glantz ◽  
R. M. Townsend ◽  
...  

We determined the mechanical and metabolic effects of graded myocardial ischemia in 23 open-chest, anesthetized pigs. By connecting the midportion of the left anterior descending artery (LAD) to the carotid artery via a constant volume, calibrated pump, we reduced the flow in the LAD to 0, 25, 50, and 75% of control rates for periods of 1 h. Flows of 100% and 150% were also examined. Using pairs of ultrasonic crystals to measure segment dimensions, we calculated segment shortening and thickening, and total and systolic stroke work in the ischemic and normally perfused segments. Blood gases, pH, and lactate and inosine balances were determined from the regional coronary venous blood. At coronary blood flows of 0, 25, 50, and 75% of normal resting flow, total segment work was 8 +/- 8, 25 +/- 4, 51 +/- 5, and 80 +/- 6% of control, respectively, while systolic segment work was -2 +/- 5, -10 +/- 5, 40 +/- 5, and 86 +/- 7% of control, respectively (means +/- SE). Thus, the decrease in total segment stroke work is proportional to the decrease in flow over the range 0-100%. However, no useful work (i.e., systolic work) is done until flow exceeds 25%. Segment shortening and thickening are significantly depressed with flows diminished by only 25%. Segmental inosine production correlates with lactate production and parallels decreased mechanical performance.


1991 ◽  
Vol 260 (2) ◽  
pp. E232-E237 ◽  
Author(s):  
T. Brundin ◽  
J. Wahren

Pulmonary, splanchnic, and interscapular O2 uptake was studied in 14 male volunteers before and for 90 min after a mixed meal. Thermistor catheters were inserted into a hepatic vein, the azygous vein, the pulmonary artery, and the aorta. Systemic and regional blood flows were determined during indirect calorimetry measurements and recordings of blood temperature. After the meal, pulmonary O2 uptake rose by 33-49 ml/min and splanchnic O2 uptake increased by 16-25 ml/min. In the azygous region O2 uptake did not increase significantly. Cardiac output increased after the meal by 1.1-1.5 l/min and splanchnic blood flow rose by 0.4-0.9 l/min. Azygous venous blood flow increased from 130 +/- 19 ml/min to 163 +/- 23 ml/min. In relation to splanchnic O2 uptake, the blood-drained splanchnic heat was low, 11 +/- 1 J/ml, and decreased to 7 +/- 1 J/ml after the meal. We conclude that after a mixed meal approximately one-half of the rise in O2 uptake occurs in the splanchnic organs; azygous-drained tissues, including possible interscapular brown adipose tissue, contribute minimally. The amount of heat drained with blood from the splanchnic region was low in relation to the splanchnic O2 uptake, indicating that splanchnic heat may be dissipated by routes other than the perfusing blood.


1991 ◽  
Vol 81 (2) ◽  
pp. 169-175 ◽  
Author(s):  
A. M. Cooper ◽  
G. D. Braatvedt ◽  
M. I. Qamar ◽  
H. Brown ◽  
D. M. Thomas ◽  
...  

1. The effects of the subcutaneous administration of a long-acting somatostatin analogue (octreotide) or of placebo on the splanchnic blood flow response to a mixed solid meal has been examined in eight normal subjects by using a transcutaneous Doppler ultrasound technique. Each subject was studied on two occasions more than 1 week apart. 2. On the control day, feeding had a pronounced effect on both superior mesenteric artery and portal venous blood flows, causing a peak rise of 82% in superior mesenteric artery blood flow at 15 min and of 75% in portal venous blood flow at 30 min post-prandially (P < 0.001). Blood flows remained elevated 2 h after the meal. Pulse and blood pressure showed no significant changes from baseline. 3. Octreotide reduced fasting superior mesenteric artery blood flow by 59% (P < 0.05) and portal venous blood flow by 49% (P < 0.01) and blunted the normal post-prandial rise. Pulse and blood pressure did not change in response to either the injection or the ingestion of the meal. 4. Octreotide suppressed the release of insulin, glucagon and pancreatic polypeptide in response to feeding and resulted in post-prandial hyperglycaemia. 5. The mechanism of action of octreotide on splanchnic blood flow is uncertain. It may be mediated via a direct vascular effect or it may act via suppression of vasoactive intestinal hormones.


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