Handling of tracer norepinephrine by the dog liver

Goresky, Carl A.; Bach, Glen G.; Cousineau, Denis; Schwab, Andreas; Rose, Colin P.; Lee, S.; Goresky, S.

doi:10.1152/ajpgi.1989.256.1.g107

Cited by 8 publications

(7 citation statements)

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“…In the denervated isolated perfused rat liver, norepinephrine hepatic clearance ranges from 0.63 to 0.74 ml/min/g liver in the physiological range of concentration (10-9-10 -8 M) (Ballet et al, 1985). These values are close to those calculated from the study of Goresky in dogs (Goresky et al, 1989), (0.80-0.89ml/min/g liver) and to those estimated by Esler in man (0.535 1/min) (Esler et al, 1984). It has been estimated that norepinephrine hepatosplanchnic clearance represents 25% of total plasma norepinephrine clearance (Esler et al, 1984).…”

Section: Hepatic Nervessupporting

confidence: 88%

Hepatic circulation: Potential for therapeutic intervention

Ballet

1990

Pharmacology & Therapeutics

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In recent years, knowledge of the physiology and pharmacology of hepatic circulation has grown rapidly. Liver microcirculation has a unique design that allows very efficient exchange processes between plasma and liver cells, even when severe constraints are imposed upon the system, i.e. in stressful situations. Furthermore, it has been recognized recently that sinusoids and their associated cells can no longer be considered only as passive structures ensuring the dispersion of molecules in the liver, but represent a very sophisticated network that protects and regulates parenchymal cells through a variety of mediators. Finally, vascular abnormalities are a prominent feature of a number of liver pathological processes, including cirrhosis and liver cell necrosis whether induced by alcohol, ischemia, endotoxins, virus or chemicals. Although it is not clear whether vascular lesions can be the primary events that lead to hepatocyte injury, the main interest of these findings is that liver microcirculation could represent a potential target for drug action in these conditions.

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Section: Hepatic Nervessupporting

confidence: 88%

Hepatic circulation: Potential for therapeutic intervention

Ballet

1990

Pharmacology & Therapeutics

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“…rather, also defined with respect to the celhlar volume; because this parameter is less prone to disturbances in flow (23) or vascular volume changes in response to sympathomimetic agents (27)(28)(29)(30). The products k,V,,,, and k -lVcell are tively; they have been found to be independent of flow ( timed samples; the values obtained were therefore averaged to provide a mean 5 S.D.…”

Section: Resultsmentioning

confidence: 99%

Salicylamide sulfate cell entry in perfused rat liver: A multiple-indicator dilution study

Schwab

Barker

et al. 1994

Hepatology

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The hepatocellular entry of salicylamide sulfate conjugate, which binds to both red blood cells and albumin, was examined with the multiple-indicator dilution technique in the perfused rat liver, with medium containing both 20% red cells and 1% albumin (set A), red cells only (set B), albumin only (set C) and neither red cells nor albumin (set D). [14C]Salicylamide sulfate, 51Cr-labeled red cells (a vascular reference), 125I-labeled albumin, [3H]sucrose or [58Co] ethylenediaminetetraacetic acid (EDTA) (high and low molecular weight interstitial references, respectively) and 3H2O or D2O (a cellular reference) were injected as a bolus into the portal vein. Among all sets of outflow data, the earliest immediate vascular recoveries for the [14C] salicylamide sulfate were lower than those for the vascular reference. For sets A and B, the upslopes precessed those for the 58Co-EDTA curve, then crossed over the 58Co-EDTA curves, with lower magnitude peaks occurring at the same time as those for labeled albumin, whereas for sets C and D, in which red cells were absent, the upslopes of [14C]salicylamide sulfate lagged behind those for labeled albumin and [3H]sucrose, reaching lower magnitude peaks coincidental in time with those for labeled sucrose. The precession of the [14C]salicylamide sulfate curve over 58Co-EDTA or [3H]sucrose in the presence (sets A and B) but not in the absence (sets C and D) of red cells and the absence of precession with albumin alone (set C) suggest that a red cell effect on the upslope is more evident than that for albumin. For all experiments, the downslopes of the sulfate curve crossed over those of the labeled red cells, albumin, 58Co-EDTA and sucrose curves and then the water curve at around the peak. The downslopes of the [14C]salicylamide sulfate were similar to those for labeled water, suggesting rapid cellular influx and efflux of salicylamide sulfate. Quantitative evaluation with a barrier-limited space-variable transit-time model for rapidly equilibrating red cell and albumin binding accounted for the upslope effects on [14C]salicylamide sulfate behavior and demonstrated its relatively high liver cell permeability. Values for the unbound permeability surface area product (0.029 to 0.036 ml sec-1.gm-1) were not different, regardless of the presence or absence of red cells and albumin, and slightly exceeded values for hepatic blood flow (0.0186 +/- 0.0016 ml sec-1.gm-1). Comparable influx (0.083 to 0.14 sec-1) and efflux (0.10 to 0.18 sec-1) coefficients were obtained, suggesting rapid cellular entry and efflux of salicylamide sulfate.(ABSTRACT TRUNCATED AT 400 WORDS)

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“…This allows determination of the mean transit time (e.g. Besides capillary permeability the multi-indicator technique gave information on the extracellular space, other volumes and metabolic turnover of tracers and indicators, and later in the 1980s, the technique gave information on, for example synaptic transmitters and other neurotransmitters (Goresky, 1963;Goresky et al, 1989), see Fig. This is derived from the central kinetic dogma: volume = flow 9 mean transit time (Lassen & Perl, 1979).…”

Section: Indicator Concentrationmentioning

confidence: 99%

“…In cardiac insufficiency, there is a changed sucrose space and reduced noradrenaline extraction. Redrawn from Goresky et al (1989).…”

Section: Indicator Concentrationmentioning

confidence: 99%

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A century of indicator dilution technique

Henriksen

Jensen

Larsson

2013

Clin Physio Funct Imaging

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This review imparts the history and the present status of the indicator dilution technique with quantitative bolus injection. The first report on flow measurement with this technique appeared 100 years ago. In 1928, the use of intravascular dyes made possible a widespread application in animals and human during the next decades. Multiple indicators, radioactive tracers, inlet-outlet detection and residue detection were introduced in the 1950s and 1960s, and refined along with the development of indicator kinetics. From the 1970s, a wide clinical use in the study of heart, brain, lungs, liver and kidneys developed, and powerful computers in the 1980s and 1990s accorded the technique a new dimension. Today, the indicator dilution technique, on one hand, is applied in the same way as 100 years ago, on the other hand it forms the basis of quantitative SPECT, positron emission tomography, and dynamic MR scans. The technique still undergoes refinement and elaboration as a lasting concept with a high potential for further development.

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Handling of tracer norepinephrine by the dog liver

Cited by 8 publications

References 0 publications

Hepatic circulation: Potential for therapeutic intervention

Hepatic circulation: Potential for therapeutic intervention

Salicylamide sulfate cell entry in perfused rat liver: A multiple-indicator dilution study

A century of indicator dilution technique

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