Effects of a Meal on Plasma Clearance of [14C]Glycocholic Acid and Indocyanine Green in Man

1981 ◽  
Vol 61 (3) ◽  
pp. 325-330 ◽  
Author(s):  
J. H. Marigold ◽  
I. T. Gilmore ◽  
R. P. H. Thompson
Keyword(s):  
Indocyanine Green ◽  
Plasma Clearance ◽  
Enterohepatic Circulation ◽  
Liver Blood Flow ◽  
Normal Subjects ◽  
Volume Of Distribution ◽  
Blue Dye ◽  
Glycocholic Acid ◽  
Disappearance Curve ◽  
Plasma Disappearance Curve

1. The fasting plasma disappearance curve of [14C]glycocholic acid after intravenous injection was compared in nine normal subjects with that obtained 100 min after a standard liquid test meal. 2. Plasma disappearance curves of indocyanine green were determined in 13 normal subjects under the same conditions. 3. Plasma clearances were significantly increased after the meal for both [14C]glycocholic acid (median 455 ml min−1 m−2, range 376–672 increased to 704, 528–1968; P < 0.01) and indocyanine green (359, 227–473 increased to 435, 358–985; P < 0.01). 4. Median initial volume of distribution was unaltered, but in four subjects it was greatly increased after the meal, although no alteration in plasma volume, measured with Evans blue dye, was observed. 5. The increased postprandial plasma clearance of glycocholic acid is probably due to an increase in liver blood flow, and suggests that in health this part of the enterohepatic circulation of bile acids also varies with meals.

Clearance and Non-Invasive Determination of the Hepatic Extraction of Indocyanine Green in Baboons and Man

1983 ◽  
Vol 64 (2) ◽  
pp. 207-212 ◽  
Author(s):  
S. L. Grainger ◽  
P. W. N. Keeling ◽  
I. M. H. Brown ◽  
J. H. Marigold ◽  
R. P. H. Thompson
Keyword(s):  
Indocyanine Green ◽  
Accurate Determination ◽  
Liver Blood Flow ◽  
Compartment Model ◽  
Hepatic Extraction ◽  
Non Invasive ◽  
Two Compartment Model ◽  
Hepatic Extraction Ratio ◽  
Plasma Disappearance Curve

1. The disposition of an intravenous bolus of indocyanine green (ICG) has been studied in healthy man and baboons using a novel analysis of a two compartment pharmacokinetic model. 2. This analysis enabled the hepatic extraction ratio (ER) of dye to be determined solely from the plasma disappearance curve, and the ER determined did not differ from that measured by hepatic vein catheterization. 3. When compared with clearance measured at steady state, the two compartment model gave a significantly more accurate determination of plasma clearance than did the conventional one compartment model. 4. It is concluded that, in health, liver blood flow may be calculated accurately and noninvasively after a single intravenous injection of ICG.

Hepatic removal of two fractions of indocyanine green after bolus injection in anesthetized pigs

1994 ◽  
Vol 266 (6) ◽  
pp. G1108-G1122 ◽  
Author(s):  
P. Ott ◽  
S. Keiding ◽  
A. H. Johnsen ◽  
L. Bass
Keyword(s):  
Indocyanine Green ◽  
Bolus Injection ◽  
Plasma Concentrations ◽  
Hepatic Uptake ◽  
Hepatic Extraction ◽  
First Order ◽  
Extraction Fraction ◽  
Disappearance Curve ◽  
Detailed Mathematical Analysis ◽  
Plasma Disappearance Curve

In the anesthetized pig, we studied the kinetics after intravenous bolus injection of two fractions of indocyanine green (ICG): the genuine ICGg (95-99% of total) and a degradation product, ICGdp (1-5%). Plasma concentrations were followed in the carotid artery and a hepatic vein. ICGg disappearance curves (n = 7) were biexponential with rate constants alpha = 0.189 +/- 0.021 min-1 and beta = 0.0356 +/- 0.0061 min-1. The hepatic extraction fraction was constant with time. A detailed mathematical analysis showed this to be in disagreement with the conventional assumption that the biexponential plasma disappearance curve is a result of backflux from the liver storage to plasma. In contrast, our observations were predicted by an alternative model assuming temporary extrahepatic, extravasal redistribution during first-order, one-way hepatic uptake. Nevertheless, when a large bolus of sulfobromophthalein (BSP) was injected 20 min after ICG, a net backflux of ICG could be demonstrated, presumably due to countertransport. Thus a sufficient description of ICGg kinetics must include the complex kinetic behavior of the hepatic membrane carrier involved. Mass spectrometry suggested that ICGdp is formed by two ICGg molecules. Plasma elimination of ICGdp was slower (alpha = 0.0094 +/- 0.0007 min-1). Analysis of the bile after bolus injection (n = 2) of ICGdp revealed two possible metabolites of ICGdp that were not found in urine. Since BSP injection did not alter the ICGdp disappearance curve, ICGdp is probably not taken up by the same hepatic membrane carrier as ICGg.

scholarly journals Erythropoietin kinetics in rats: generation and clearance

Blood ◽  
1986 ◽  
Vol 67 (3) ◽  
pp. 646-649 ◽  
Author(s):  
SE Steinberg ◽  
JF Garcia ◽  
GR Matzke ◽  
J Mladenovic
Keyword(s):  
Intravenous Injection ◽  
Plasma Volume ◽  
Rat Model ◽  
Clearance Rate ◽  
Half Life ◽  
Plasma Clearance ◽  
Compartment Model ◽  
Volume Of Distribution ◽  
Two Compartment Model ◽  
Disappearance Curve

Abstract Detailed studies to analyze the early events of erythropoietin (Ep) secretion and clearance were performed in a rat model using a double antibody radioimmunoassay. Ep clearance was determined following intravenous injection of 1 mL of Ep-rich plasma, 1,080 mU/mL, obtained from phlebotomized rats. Analysis revealed a disappearance curve that conformed to a two-compartment model with an alpha half-life t1/2 of 3.6 minutes and a beta t1/2 of 86 minutes. The volume of distribution was similar to the calculated plasma volume. In anephric animals, there was no change in the plasma clearance rate or the volume of distribution. Rapid Ep secretion was elicited by a single 15 mL/kg phlebotomy (hematocrit decrement 45% to 30%), so that levels reached 20 to 30 times baseline (524 +/- 76 v 24 +/- 7 mU/mL) at five hours, whereas they plateaued for at least 33 hours. The increase in the rate of secretion was geometric, from 9.9 mU/h baseline secretion to 429 mU/h. These data identify a very sensitive and rapidly responsive system for Ep modulation in the rat.

Direct Measurement of Hepatic Extraction of Bile Acids in Subjects with and without Liver Disease

1981 ◽  
Vol 60 (1) ◽  
pp. 65-72 ◽  
Author(s):  
I. T. Gilmore ◽  
R. P. H. Thompson
Keyword(s):  
Liver Disease ◽  
Indocyanine Green ◽  
Bile Acids ◽  
Cholic Acid ◽  
Enterohepatic Circulation ◽  
Extraction Ratio ◽  
Constant Infusion ◽  
Hepatic Extraction ◽  
Glycocholic Acid ◽  
Hepatic Extraction Ratio

1. The hepatic extraction ratio of 14C-labelled bile acids has been measured directly by hepatic vein catheterization in five patients without liver disease (glycocholic acid, three; cholic acid, two) and in 16 patients with histologically confirmed liver disease (glycocholic acid, seven; cholic acid, nine). 2. After intravenous administration of [14C]-glycocholic acid by bolus injection (two control subjects) or constant infusion (one control subject), directly measured hepatic extraction ratio was 0.91, 0.84 and 0.88, greater than that for indocyanine green. The extraction ratio of [14C]cholic acid in two subjects was 0.72 and 0.70, confirming a lower extraction of the unconjugated bile acid. 3. The hepatic extraction ratio of both bile acids was reduced in patients with chronic liver disease (range 0.07–0.69), although the extraction ratio of glycocholic acid remained normal in one patient with viral hepatitis. 4. Estimates of liver flow calculated from the extraction of [14C]glycocholic acid, but not cholic acid, correlated with those calculated from indocyanine green kinetics, although numbers were small. 5. Measurement of the hepatic extraction of individual bile acids, not previously reported in man, allows a more accurate description of the enterohepatic circulation.

Disappearance of palmitic acid from plasma of fetal and newborn sheep

1993 ◽  
Vol 74 (1) ◽  
pp. 62-67 ◽  
Author(s):  
G. G. Power ◽  
Y. Yoneyama ◽  
H. Asakura ◽  
R. Sawa
Keyword(s):  
Palmitic Acid ◽  
Clearance Rate ◽  
Half Life ◽  
Plasma Clearance ◽  
Exponential Model ◽  
Volume Of Distribution ◽  
Membrane Transporter ◽  
Double Exponential ◽  
Disappearance Curve ◽  
Double Exponential Model

These studies were undertaken to measure the kinetic constants that characterize the disappearance of a representative free fatty acid (FFA) from the plasma of fetal and newborn sheep. A bolus of albumin-complexed [14C]palmitic acid was infused intravenously, and during the next 8 min, 24 arterial samples were collected to characterize the disappearance curve. Palmitic acid disappearance from plasma was well described by a double-exponential model. When birth was simulated in utero, kinetic values were not changed by cooling. However, after intrauterine ventilation with O2, the volume of distribution of the FFA increased 29%, its plasma clearance rate decreased 26%, and its apparent half-life in the plasma lengthened from 0.8 to 1.2 min (all P < 0.01, n = 8). After umbilical cord occlusion, plasma clearance rate decreased a further 19% and half-life lengthened to 1.4 min. About 60% of the increase in FFA concentration during simulated birth is explained by increased release from adipose stores, and 40% is explained by decreased clearance. Further experiments tested the influence of FFA concentrations themselves. After infusion of unlabeled FFA, clearance of the tracer decreased 23% (P < 0.05, n = 5), a result consistent with a saturable membrane transporter of FFAs.

Hepatic clearance of rat plasma intestinal alkaline phosphatase

1984 ◽  
Vol 247 (4) ◽  
pp. G419-G426 ◽  
Author(s):  
G. P. Young ◽  
I. S. Rose ◽  
S. Cropper ◽  
S. Seetharam ◽  
D. H. Alpers
Keyword(s):  
Alkaline Phosphatase ◽  
Biliary Excretion ◽  
Enterohepatic Circulation ◽  
Hepatic Clearance ◽  
Rat Plasma ◽  
Intestinal Alkaline Phosphatase ◽  
Rapid Clearance ◽  
Specific Receptors ◽  
Disappearance Curve ◽  
Plasma Disappearance Curve

The mechanism and route of clearance of intestinal alkaline phosphatase from plasma have been studied in rats to define the magnitude of hepatic extraction and biliary excretion of the enzyme. Plasma clearance, tissue distribution, and biliary excretion of enzyme were followed after intravenous administration of physiological amounts of 125I-labeled rat intestinal alkaline phosphatase. The plasma disappearance curve was biphasic; the initial phase was rapid, during which 50% of injected enzyme was selectively extracted by the liver over 5 min. Less than 4% of total hepatic radioactivity was excreted into bile over 80 min; this was shown by chromatographic analysis to be degraded enzyme only. Rapid clearance of enzyme could be significantly slowed by injection of large amounts of mannan or N-acetylglucosamine-bovine serum albumin, but not by desialylated fetuin, demonstrating that clearance was probably mediated by mannose/N-acetylglucosamine-specific receptors. It is concluded that, under physiological conditions, rat plasma intestinal alkaline phosphatase is rapidly cleared from the circulation by the liver. However, biliary excretion of undergraded enzyme is negligible, and a physiologically significant enterohepatic circulation seems most unlikely.

Disposal and distribution of rT3 in humans: a new double-tracer kinetic study

1993 ◽  
Vol 264 (2) ◽  
pp. E239-E249 ◽  
Author(s):  
A. Pilo ◽  
G. Iervasi ◽  
F. Vitek ◽  
S. Turchi ◽  
R. Bianchi
Keyword(s):  
Experimental Data ◽  
Compartment Model ◽  
Normal Subjects ◽  
Peripheral Tissues ◽  
Experimental Base ◽  
Tracer Kinetic ◽  
Disappearance Curve ◽  
Definition Of ◽  
Plasma Disappearance Curve

A satisfactory definition of reverse 3,3',5'-triiodothyronine (rT3) kinetics in humans cannot be obtained if the plasma disappearance curve of the injected labeled hormone is the only experimental data available; most of the kinetic parameters can only be bounded within ranges showing unacceptable variabilities. To gain additional experimental data a double-tracer approach is proposed. After simultaneous injection of [125I]rT3 and 131I the following three experimental curves were determined in plasma: 1) the disappearance of [125I]rT3, 2) the disappearance of 131I, and 3) the appearance of 125I generated in vivo from labeled rT3 degradation. Combined analysis of these three curves, based on a complex six-compartment model, was developed and applied to data obtained in a group of normal subjects. Through this new analysis, fractional disposal rates and fractional exchange rates between the plasma compartment and the periphery are uniquely determined. The main physiologically interesting information on the degradation of the hormone that emerges from these studies are 1) all degradative pathways of rT3 generate iodide, being in all cases the [125I]rT3 dose completely recovered as 125I in plasma; and 2) most rT3 is degraded (65–90%) in peripheral tissues rapidly exchanging with the plasma pool. The extended experimental base is not yet sufficient to compute unique values for production rate (PR) and body mass (Qt); the validity of estimates of PR and Qt is based on the assumption that injected [125I]rT3 is able to trace all rT3 peripherally produced (from thyroxine). The new approach yields ranges for PR and Qt (1.12–2.15 micrograms/h and 2.88–8.24 micrograms) much narrower than those computable from the [125I]rT3 disappearance curve only (1.12–5.07 micrograms/h for PR and 2.88-23.7 micrograms for Qt).

Hepatic uptake and biliary excretion of Indocyanine green and its use in estimation of hepatic blood flow in dogs

1960 ◽  
Vol 199 (3) ◽  
pp. 481-484 ◽  
Author(s):  
Sigmund G. Ketterer ◽  
Bernard D. Wiegand ◽  
Elliot Rapaport
Keyword(s):  
Blood Flow ◽  
Indocyanine Green ◽  
Plasma Volume ◽  
Biliary Excretion ◽  
Liver Blood Flow ◽  
Hepatic Function ◽  
Volume Of Distribution ◽  
Hepatic Uptake ◽  
Constant Infusion ◽  
Volume Recovery

Indocyanine green when injected intravenously into normal dogs rapidly disappears, after mixing, from the circulation in an initial exponential fashion. This property enables one to calculate its original volume of distribution and its clearance from the circulation. The initial volume of distribution corresponded closely with the circulating plasma volume. Recovery of the dye from surgically created biliary fistulas approached 100% of the injected amounts and averaged 91%. During constant infusion, significant hepatic arteriovenous differences in dye concentrations occurred, making it possible to calculate hepatic clearances, extraction ratios and liver blood flow. The values obtained by the latter method agreed well with those obtained following single injections. The virtually complete hepatic uptake of Indocyanine green, ease of quantitative plasma and biliary determinations and its exponential loss from the circulation with a short half-life provide advantages over previously used substances in evaluating hepatic function and blood flow.

Hepatic blood flow and metabolism in severe falciparum malaria: clearance of intravenously administered galactose

1992 ◽  
Vol 82 (1) ◽  
pp. 63-70 ◽  
Author(s):  
S. Pukrittayakamee ◽  
N.J. White ◽  
T. M. E. Davis ◽  
S. Looareesuwan ◽  
W. Supanaranond ◽  
...  
Keyword(s):  
Blood Flow ◽  
Indocyanine Green ◽  
Falciparum Malaria ◽  
Plasma Clearance ◽  
Plasma Concentrations ◽  
Liver Blood Flow ◽  
Severe Infection ◽  
Acute Illness ◽  
Plasma Lactate ◽  
Severe Falciparum Malaria

1. Hypoglycaemia and lactic acidosis are important manifestations of severe falciparum malaria. To investigate hepatic gluconeogenesis in acute falciparum malaria, liver blood flow and galactose clearance were estimated in seven adult patients with moderately severe infection and seven patients with severe infection (three of whom died later). Nine patients were restudied in convalescence. 2. Liver blood flow, determined from the plasma clearance of Indocyanine Green, was lower in acute illness than in convalescence [16.1 (7.0) versus 23.9 (7.2) ml min−1 kg−1, mean (sd)], but this difference was not statistically significant (P= 0.15). There was a significant inverse correlation between admission venous plasma lactate concentrations and the liver blood flow estimated from the clearance of Indocyanine Green (rs = 0.71, P = 0.004). 3. The plasma clearance of galactose after intravenous injection was similar in the acute [15.4 (4.90) ml min−1 kg−1] and convalescent study [12.8 (2.1) ml min−1 kg−1]. The ratio of galactose clearance to Indocyanine Green clearance was significantly higher in acute disease [1.41 (0.51)] than in convalescence [0.70 (0.34)], largely because of the elevated ratios in severely ill patients [1.48 (0.50)]. 4. The rise in blood glucose concentration after galactose administration was significantly higher during acute illness [1.48 (0.72) mmol/l] than in convalescence [0.67 (0.41) mmol/l, P = 0.022], but the insulin response was similar, indicating reduced tissue insulin sensitivity. There was no significant change in the plasma concentrations of other metabolites (lactate, pyruvate, alanine and triacylglycerol) in either study. 5. These results suggest that the segment of the glycolytic pathway between galactose and glucose is unimpaired in patients with severe falciparum malaria. Since galactose does not stimulate insulin secretion directly and does not appear to increase plasma lactate concentrations, this simple sugar may be an alternative to glucose in the treatment of malaria-associated hypoglycaemia.

Fate of circulating amino-terminal propeptide of type III procollagen in conscious pigs

1993 ◽  
Vol 265 (1) ◽  
pp. R139-R145
Author(s):  
L. T. Jensen ◽  
J. H. Henriksen ◽  
J. Risteli ◽  
H. P. Olesen ◽  
M. D. Nielsen ◽  
...  
Keyword(s):  
Plasma Clearance ◽  
Initial Distribution ◽  
Initial Slope ◽  
Type Iii Collagen ◽  
Type Iii ◽  
Amino Terminal ◽  
Type Iii Procollagen ◽  
Venous Shunt ◽  
Disappearance Curve ◽  
Plasma Disappearance Curve

The amino-terminal propeptide of type III procollagen (PIIINP, M(r) 42,000) is a promising marker for the formation of type III collagen of granulation tissue in experimental and clinical studies. The disposal kinetics of circulating PIIINP is, however, almost unknown. In conscious pigs with a thoracic duct-venous shunt, 125I-labeled PIIINP was injected intravenously. The initial distribution volume was 2.2 liters, which was 1.7 times the plasma volume (P < 0.01). The disappearance curve was three-phased, with an initial steep decline (t1/2 58 min), followed by two slower phases (t1/2 239 min and 289 h). Consecutive gel filtrations showed that the initial slope of the plasma disappearance curve corresponded to the plasma clearance of the intact PIIINP. The initial plasma clearance was 26.5 ml plasma/min, whereas the urinary clearance was 8.7 ml plasma/min (P < 0.01). The other components of the plasma disappearance curve originated from the formation and disappearance of a high and a low molecular weight (MW) fraction as part of the degradation of PIIINP. The high MW fraction (approximately M(r) 90,000) was similar to a previously described, but not further characterized, PIIINP immunoreactive component. The existence of the low MW fraction (approximately M(r) 20,000) has not been reported before. The lymphatic recirculation of intact PIIINP was rapid, and the lymph-serum ratio was almost constant within 1 h of injection. We conclude that the t1/2 of circulating PIIINP is 58 min, that PIIINP escapes the circulation very quickly, and that the degradation of PIIINP includes at least two intermediary steps.

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