Journal Article•
The theory and applications of the exchange of inert gas at the lungs and tissues
About: This article is published in Pharmacological Reviews.The article was published on 1951-03-01 and is currently open access. It has received 1669 citations till now. The article focuses on the topics: Inert gas.
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TL;DR: A standard set of quantity names and symbols related to the estimation of kinetic parameters from dynamic contrast‐enhanced T1‐weighted magnetic resonance imaging data, using diffusable agents such as gadopentetate dimeglumine (Gd‐DTPA), are described.
Abstract: We describe a standard set of quantity names and symbols related to the estimation of kinetic parameters from dynamic contrast-enhanced T(1)-weighted magnetic resonance imaging data, using diffusable agents such as gadopentetate dimeglumine (Gd-DTPA). These include a) the volume transfer constant K(trans) (min(-1)); b) the volume of extravascular extracellular space (EES) per unit volume of tissue v(e) (0 < v(e) < 1); and c) the flux rate constant between EES and plasma k(ep) (min(-1)). The rate constant is the ratio of the transfer constant to the EES (k(ep) = K(trans)/v(e)). Under flow-limited conditions K(trans) equals the blood plasma flow per unit volume of tissue; under permeability-limited conditions K(trans) equals the permeability surface area product per unit volume of tissue. We relate these quantities to previously published work from our groups; our future publications will refer to these standardized terms, and we propose that these be adopted as international standards.
3,078 citations
Cites background or methods from "The theory and applications of the ..."
...Following the approach of Kety (3), we assume tracer flux into the EES is proportional to the difference between plasma and EES concentrations:...
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...Note that Kety (3) used F to denote total flow of blood (ml min21); some workers have used F to denote plasma flow per unit volume of tissue (this is Fr(1 2 Hct) in our nomenclature)....
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...Flow-Limited Kety Model (3) (High Permeability)...
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...Kety (3,9,13) produced a model of flow-limited tracer uptake in tissue that has been used extensively....
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...The subscripts are in lower case, according to widespread previous use (3,6), although some pharmacokinetic work has used upper case (11)....
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TL;DR: Iodo[14C]antipyrine appears, therefore, to be a satisfactory nonvolatile tracer for the measurement of local cerebral blood flow.
Abstract: The autoradiographic diffusible tracer technique for the measurement of local cerebral blood flow was originally designed for use with the radioactive, inert gas 131I-labeled trifluoroiodomethane and is applicable only with tracers that exhibit unrestricted diffusion through the blood-brain barrier. Because of the technical problems associated with the use of gaseous tracers, a suitable nonvolatile tracer has been sought. [14C] Antipyrine has been used previously and found to be unsuitable because of limitations in its diffusion through the blood-brain barrier. An analogue of [14C]antipyrine, iodo [14C]antipyrine, exhibits higher partition coefficients than [14C]antipyrine between nonpolar solvents and water and might, therefore, be expected to diffuse more freely through the barrier. Its use as the tracer in the local blood flow technique leads to values considerably above those obtained with [14C]antipyrine in the rat and cat and essentially the same as those obtained with the gas trifluoro[131I]iodomethane in the cat. Iodo[14C]antipyrine appears, therefore, to be a satisfactory nonvolatile tracer for the measurement of local cerebral blood flow.
1,032 citations
TL;DR: The main virtue of this method lies in the fact that repeated measurements of local blood flow can be obtained without access to arterial or local venous blood, which also provides information on the distribution of blood flow.
Abstract: When a platinized platinum electrode is polarized at the potential of the standard calomel electrode, the current generated is proportional to the concentration of dissolved hydrogen gas. The effects of physiological variations in oxygen tension, pH, temperature, and ascorbic acid concentration were found to be negligible. Although absolute calibration in vivo is not possible, the rate of tissue hydrogen saturation or desaturation can be measured by needle-shaped electrodes inserted into the tissue. Arterial and venous concentration can be measured with catheter electrodes. Solubility of hydrogen gas in kidney slices was found to be the same as in blood. With the assumption that tissue is in instantaneous diffusion equilibrium with local venous blood with respect to hydrogen, the local blood flow per volume of tissue can be calculated according to the Fick principle from the rate of tissue desaturation when arterial concentration is lowered to zero. The method was tested on dogs in myocardium, kidney, and skeletal muscle. Hydrogen was administered by respiration or by intra-arterial infusion of hydrogen-saturated saline, giving an arterial concentration of 3% to 5% saturation. Tissue desaturation curves were recorded simultaneously from two to three tissue electrodes. Good agreement with flow measured simultaneously with other methods was obtained in myocardium and renal cortex, while the data on skeletal muscle do not permit any definite conclusion. The main virtue of this method lies in the fact that repeated measurements of local blood flow can be obtained without access to arterial or local venous blood. Reliable measurements of regional blood flow were also obtained from continuously recorded venous desaturation curves, which also provide information on the distribution of blood flow.
951 citations
TL;DR: An in vivo method for use with positron emission tomography (PET) that results in a quantitative characterization of neuroleptic binding sites using radiolabeled spiperone, the first direct evidence that PET can be used to characterize quantitatively, locally and in vivo, drug binding sites in brain.
Abstract: We propose an in vivo method for use with positron emission tomography (PET) that results in a quantitative characterization of neuroleptic binding sites using radiolabeled spiperone. The data are analyzed using a mathematical model that describes transport, nonspecific binding, and specific binding in the brain. The model demonstrates that the receptor quantities Bmax (i.e., the number of binding sites) and KD-1 (i.e., the binding affinity) are not separably ascertainable with tracer methodology in human subjects. We have, therefore, introduced a new term, the binding potential, equivalent to the product BmaxKD-1, which reflects the capacity of a given tissue, or region of a tissue, for ligand-binding site interaction. The procedure for obtaining these measurements is illustrated with data from sequential PET scans of baboons after intravenous injection of carrier-added (18F)spiperone. From these data we estimate the brain tissue nonspecific binding of spiperone to be in the range of 94.2 to 95.3%, and the regional brain spiperone permeability (measured as the permeability-surface area product) to be in the range of 0.025 to 0.036 cm3/(s X ml). The binding potential of the striatum ranged from 17.4 to 21.6; these in vivo estimates compare favorably to in vitro values in the literature. To ourmore » knowledge this represents the first direct evidence that PET can be used to characterize quantitatively, locally and in vivo, drug binding sites in brain. The ability to make such measurements with PET should permit the detailed investigation of diseases thought to result from disorders of receptor function.« less
951 citations
TL;DR: A method is described for estimating the clearance rate and fractional blood flow of the fast (gray matter) compartment of the brain from the first ten minutes of 122 XE clearance curves, following a one-minute inhalation.
Abstract: A method is described for estimating the clearance rate and fractional blood flow of the fast (gray matter) compartment of the brain from the first ten minutes of 133Xe clearance curves, following a one-minute inhalation. Computer-simulated data were used to test the adequacy of the two-compartmental model employed, and to evaluate the stability of the parameters in the presence of random noise. A comparison was made between this approach and the previously reported three-compartmental analysis. Regional cerebral blood flow data were obtained on 48 young control subjects and 20 elderly demented patients. Hemispheral regional, and test-retest variations were determined, as well as differences between the groups.
864 citations