Hepatic blood flow: accuracy of estimation from galactose clearances in cats

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.

1988 ◽  
Vol 66 (9) ◽  
pp. 1192-1197 ◽  
Author(s):  
C. V. Greenway ◽  
W. W. Lautt ◽  
D. S. Sitar

Experiments were carried out to determine the accuracy and validity of estimations of hepatic blood flow from systemic clearances of ethanol during very low dose (8 μmol∙min−1∙kg−1) infusions of ethanol in anesthetized cats. Systemic clearances were compared with directly measured hepatic blood flow using a hepatic venous long-circuit technique. This technique allowed direct measurement and alteration of hepatic blood flow and collection of arterial, portal, and hepatic venous blood samples without depletion of the animal's blood volume. In 18 cats, Vmax for ethanol was 93 ± 7 μmol∙min−1 per 100 g liver or 21 ± 2 μmol∙min−1∙kg·body weight−1 and Km was 144 ± 19 μM in terms of logarithmic mean sinusoidal concentration. At the dose of 8 μmol∙min−1∙kg body weight−1 used for estimation of hepatic blood flow, extraction was 0.95 ± 0.07 (mean ± SD). Systemic clearance of ethanol overestimated directly measured hepatic blood flow by 15 ± 16%. Hepatic blood flow changes expressed as percentages of the control level were accurately estimated from systemic ethanol clearance (100 ± 10%). Since 73 ± 12% of the infused ethanol was eliminated by the liver and 83 ± 11% was eliminated by the splanchnic bed, an extrasplanchnic uptake of 17% accounted for the overestimation of hepatic blood flow. Estimation of hepatic blood flow from systemic clearances of ethanol during very low dose infusions may have advantages over other clearance methods. Its use in cats was illustrated in a separate series of experiments and it was shown that surgery significantly reduced hepatic blood flow. The method may merit trial for estimation of hepatic blood flow in humans.


1977 ◽  
Vol 53 (5) ◽  
pp. 411-418 ◽  
Author(s):  
L. Sestoft ◽  
J. Trap-Jensen ◽  
J. Lyngsøe ◽  
J. P. Clausen ◽  
J. J. Holst ◽  
...  

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.


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.


1987 ◽  
Vol 252 (5) ◽  
pp. H953-H962 ◽  
Author(s):  
F. J. Burczynski ◽  
K. L. Pushka ◽  
D. S. Sitar ◽  
C. V. Greenway

Experiments were performed to determine the validity of the indocyanine green (ICG) clearance technique, with and without allowances for incomplete hepatic extraction, as an estimate of hepatic plasma flow. This technique was compared with that of directly measured hepatic blood flow using a hepatic venous long-circuit preparation in the anesthetized cat. This preparation allowed direct measurement and alteration of hepatic blood flow and collection of arterial, portal, and hepatic venous blood samples without depletion of the animal's blood volume. Measurements of ICG by spectrophotometry and high-pressure liquid chromatography (HPLC) were equally accurate, but the HPLC was 100 times more sensitive and allowed smaller sample volumes. It was determined that systemic clearance of ICG after a bolus dose (1.3 mumol/kg) was much smaller than hepatic blood flow. Allowance must be made for the incomplete extraction. When the clearance was multiplied by extraction, mean estimated hepatic plasma flow exceeded the measured flow values by 20-30%, and this difference was attributed to temporary extrahepatic distribution. In all experiments estimated hepatic plasma flows were highly variable, and reasons for this are discussed. In hepatectomized cats ICG was found to be distributed into extrahepatic tissues.


1987 ◽  
Vol 252 (5) ◽  
pp. G648-G653
Author(s):  
S. Gelman ◽  
E. Dillard ◽  
D. A. Parks

The present study was performed on eight young pigs to test the hypothesis that glucagon increases hepatic oxygen supply to a greater extent than hepatic oxygen uptake, providing a better hepatic oxygen supply-demand relationship. The experiments were performed under pentobarbital sodium anesthesia and controlled ventilation. Splanchnic blood flow was studied using radioactive microspheres. Glucagon was administered in doses of 1 and 5 micrograms X kg-1 X min-1. During glucagon infusion, hepatic arterial blood flow substantially increased, splenic and pancreatic blood flows increased moderately, while stomach and intestinal blood flows, as well as portal blood flow did not change significantly. Shunting of both 9- and 15-micron spheres through preportal tissues did not change significantly. Oxygen content in arterial or portal venous blood did not change significantly, while it increased in hepatic venous blood by 30%. There were no differences in the effects between the doses of glucagon administered. There was no correlation found between changes in hepatic oxygen supply and cardiac output or blood pressure. The changes observed during glucagon administration resulted in an increase in oxygen delivery to the liver and hepatic oxygen supply-uptake ratio.


1988 ◽  
Vol 255 (3) ◽  
pp. H563-H568
Author(s):  
C. D. Kurth ◽  
L. C. Wagerle ◽  
M. Delivoria-Papadopoulos

We examined cerebral blood flow (CBF) regulation by the sympathetic nerves in 12 newborn lambs (3–11 days old) during seizures, a potent reflex stimulator of the sympathetic nervous system. CBF was measured with microspheres, and seizures were induced with bicuculline. In six of these lambs, one hemibrain was denervated (D) chronically by interrupting the ipsilateral cervical sympathetic trunk; the other hemibrain remained innervated (I). Before and after 10, 35, and 70 min of seizures, cerebral gray matter blood flow (mean +/- SE ml.min-1.100 g-1) was, respectively, 12 +/- 3 (9%), 71 +/- 12 (21%), 120 +/- 15 (38%), and 54 +/- 5 (14%) greater (P less than 0.05) in the D than in the I hemibrain. In the cerebral white matter, hippocampus, caudate, and thalamus blood flows to the D and I hemibrains were similar before seizures but during seizures they were 10–39% greater (P less than 0.05) in the D than in the I hemibrain. Midbrain, brainstem, and cerebellum D and I blood flows were always similar. In the other six lambs, acute denervation during seizures increased ipsilateral cerebral gray and hippocampus blood flow by 10–31%, but unilateral electrical stimulation decreased ipsilateral cerebral gray, cerebral white, hippocampus, thalamus, and caudate blood flow by 17–27%. The data demonstrate that, during seizures, sympathetic nerve activity modifies regional CBF and the effect is sustained, suggesting a role for the sympathetic nervous system in newborn CBF regulation.


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.


1978 ◽  
Vol 235 (2) ◽  
pp. H262-H265
Author(s):  
W. W. Lautt ◽  
C. Wong ◽  
J. S. Durham ◽  
P. Taillon

A method for obtaining pure, mixed hepatic venous blood is described and evaluated in anesthetized cats. Hepatic vascular congestion does not occur with this “intracaval cannulation”, however small elevations in central venous blood pressure were noted. Although these changes persisted they did not result in systemic vascular congestion, judging from the normal arterial and portal pressures and from the lack of progressive decrease in arterial blood pressure. Blood samples obtained using the intracaval cannulation were shown to contain identical levels of oxygen as those obtained using a more complex surgical preparation. Reflux of blood from the vena cava does not occur during sampling. The responsiveness of this sampling method to rapid changes in venous content was evaluated by following the changes in glucose balance caused by direct stimulation of the hepatic nerves. The responses measured were similar to those measured in a separate set of experiments obtained using blood samples from a surgically isolated hepatic venous supply.


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.


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.


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