Fluorodeoxyglucose rate constants, lumped constant, and glucose metabolic rate in rabbit heart

The isolated arterially perfused rabbit interventricular septum was used to measure myocardial metabolic rate for glucose (MMRGlc) and rate constants and lumped constant (LC) for the glucose analogue [18F]fluorodeoxyglucose (FDG) using a tracer kinetic model. FDG was delivered by constant infusion during coincidence counting of tissue 18F radioactivity. The MMRGlc was measured by the Fick method. Control septa were paced at 72 beats/min and perfused at 1.5 ml/min with oxygenated perfusate containing 5.6 mM glucose and 5 mU/ml insulin. The following conditions were tested: 3.0 and 4.5 ml/min; insulin increased to 25 mU/ml; insulin omitted; 2.8 mM and 11.2 mM glucose; 144 beats/min and 96 paired stimuli/min; and anoxia. Under all conditions studied the phosphorylation (hexokinase) reaction was rate limiting relative to transport. Compared with control conditions, the phosphorylation rate constant was significantly increased with 2.8 mM glucose as well as in anoxia. With 4.5 ml/min and 11.2 mM glucose, conditions that should increase glucose flux into tissue without increasing demand, the phosphorylation rate constant decreased significantly. With 11.2 mM glucose, 96 paired stimuli/min, and anoxia without insulin, a significant increase in the hydrolysis rate of FDG 6-phosphate was observed and suggests that hydrolysis is also an important mechanism for regulating the MMRGlc. Increased transport rate constants were observed with increased flow rates, 96 paired stimuli/min, and anoxia at 96 beats/min. The LC was not significantly different from control in 11 of 14 conditions studied. Therefore, under most conditions, an average LC can be used to calculate MMRGlc estimates.

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Estimation of rabbit myocardial metabolic rate for glucose using fluorodeoxyglucose

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1982.243.6.h884 ◽

1982 ◽

Vol 243 (6) ◽

pp. H884-H895 ◽

Cited By ~ 5

Author(s):

J. Krivokapich ◽

S. C. Huang ◽

M. E. Phelps ◽

J. R. Barrio ◽

C. R. Watanabe ◽

...

Keyword(s):

Kinetic Model ◽

Glucose Utilization ◽

Interventricular Septum ◽

Constant Infusion ◽

Coincidence Counting ◽

Reverse Transport ◽

Exogenous Glucose ◽

Tracer Kinetic

The isolated arterially perfused rabbit interventricular septum was used to determine the feasibility of using the glucose analogue 18F-2-deoxy-2-fluoro-d-glucose (DG) with a tracer kinetic model to estimate the rate of exogenous glucose utilization. FDG was delivered to the septum by constant infusion, and tissue 18F radioactivity was measured as a function of time by external coincidence counting. The following four conditions were studied: flow rates of 0.5, 1.0, and 1.5 ml/min with a heart rate of 72 beats/min and flow at 1.5 ml/min with 96 beats/min. The rate constants for FDG forward and reverse transport between the vascular and extravascular compartments (k*1, k*2, respectively), phosphorylation of FDG (k*3), and dephosphorylation of FDG-6-phosphate (FDG-6-P) (k*4) were determined from the tissue curves using a tracer kinetic model. The lumped constant (LC) of the deoxyglucose model calculated using Fick-derived myocardial metabolic rates of glucose (MMRGlc), was 0.60 +/- 0.10 and was stable over the range of conditions studied. Average k*'s and LC were used to calculate MMRGlc's employing the model and were not significantly (P greater than 0.05) different from those determined by the Fick method. Tissue analyses using high-pressure liquid chromatography documented that tissue 18F radioactivity wa due to FDG and FDG-6-P, and their relative fractions agreed well with the values predicted from the tracer kinetic model. Only FDG was detected in the effluent. These studies also indicate the presence of a myocardial enzyme that can hydrolyze FDG-6-P to FDG. Thus our results support the use of the FDG method with positron-computed tomography for the in vivo determination of the myocardial rate of exogenous glucose utilization.

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Time-Dependent Changes of Lumped and Rate Constants in the Deoxyglucose Method in Experimental Cerebral Ischemia

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/jcbfm.1987.117 ◽

1987 ◽

Vol 7 (5) ◽

pp. 640-648 ◽

Cited By ~ 18

Author(s):

Hirofumi Nakai ◽

Y. Lucas Yamamoto ◽

Mirko Diksic ◽

Hiroshi Matsuda ◽

Eiichi Takara ◽

...

Keyword(s):

Rate Constants ◽

Time Course ◽

Time Dependent ◽

Sham Operation ◽

Coincidence Counting ◽

Mca Occlusion ◽

Significant Difference ◽

Lumped Constant ◽

Arterial Plasma ◽

Deoxyglucose Method

Time-dependent changes in the lumped and rate constants in a bilateral middle cerebral artery (MCA) occlusion in cats were evaluated. These variables were measured in 11 cats after a sham operation, in five after a 1-h occlusion, in two after a 2-h occlusion, in five after a 4-h occlusion, and in four after a 16-h occlusion. The time course of the cerebral tissue radioactivity [Ci* ( t)] was monitored by external coincidence counting during a programmed infusion of [18F]2-fluorodeoxyglucose (FDG). Arterial plasma concentration [Cp* ( t)] of tracer was kept constant during the first 45 min. Comparison of k2* and k3* in the sham-operated group, estimated by external coincidence counting, and by the ratio of extraction fractions of glucose and [18F]2-FDG, demonstrated no significant difference between these rate constants in these two groups of animals. The rate and lumped constants were also estimated from Ci* ( t) and Cp* ( t), as well as from the ratio of extraction fractions of glucose and [18F]2-FDG, respectively, in the MCA occlusion group. Significant decrease in k3* was observed after 1 h of occlusion (20% lower than in the sham operation, p < 0.05); in ki* decrease occurred within 4 h of occlusion (21% lower than in the sham operation, p < 0.05). However, decrease in k2* was observed only after 16 h of occlusion (26% lower than in the sham operation, p < 0.05). Namely, decrease of rate constants occurred first in k3* then in k1* and k2*. In contrast to the rate constants where decrease was observed, a significant increase in the lumped constant occurred between 1 and 4 hours after occlusion (55% higher than in the 1-h occlusion, p < 0.05). However, the values of the lumped constant were not significantly different between the 4-h occlusion group and the 16-h occlusion group.

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Estimation of Local Cerebral Glucose Utilization by Positron Emission Tomography: Comparison of [18F]2-Fluoro-2-Deoxy-D-Glucose and [18F]2-Fluoro-2-Deoxy-D-Mannose in Patients with Focal Brain Lesions

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/jcbfm.1991.92 ◽

1991 ◽

Vol 11 (3) ◽

pp. 485-491 ◽

Cited By ~ 13

Author(s):

K. Wienhard ◽

G. Pawlik ◽

B. Nebeling ◽

J. Rudolf ◽

G. Fink ◽

...

Keyword(s):

Rate Constant ◽

Glucose Utilization ◽

Brain Lesions ◽

Emission Tomography ◽

Local Cerebral Glucose Utilization ◽

Regional Variability ◽

Positron Emission ◽

Lumped Constant ◽

Regional Basis ◽

Phosphorylation Rate

A comparative PET study of [18F]2-fluoro-2-deoxy-D-glucose (FDG) and [18F]2-fluoro-2-deoxy-D-mannose (FDM) uptake was performed in 13 patients with focal brain lesions. Differences between FDG and FDM with respect to model rate constants, lumped constant, and estimated metabolic rate for glucose were determined on a regional basis. Across whole brain, the transport rate constant K*1 was almost unchanged, whereas k*2, describing the transport back from tissue to plasma, was 6% higher, and the phosphorylation rate constant k*3 was 9% lower for FDM compared to FDG. This implies a 20% lower lumped constant for FDM. No significant regional variability of this differential tracer behavior was observed in normal or in lesioned brain tissue. Thus, results from previous FDG studies, where the radiotracer was not 100% pure FDG but contained varying amounts of FDM, can easily be corrected by adjustment of the lumped constant employed in metabolic quantitation.

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Alternative Approach to Single-Scan Estimation of Cerebral Glucose Metabolic Rate Using Glucose Analogs, with Particular Application to Ischemia

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/jcbfm.1984.5 ◽

1984 ◽

Vol 4 (1) ◽

pp. 35-40 ◽

Cited By ~ 72

Author(s):

G. D. Hutchins ◽

J. E. Holden ◽

R. A. Koeppe ◽

J. R. Halama ◽

S. J. Gatley ◽

...

Keyword(s):

Metabolic Rate ◽

Linear Relationship ◽

Rate Constants ◽

Glucose Utilization ◽

Tissue Concentration ◽

Accurate Estimation ◽

Transport Parameter ◽

Glucose Metabolic Rate ◽

Time Courses ◽

Phosphorylation Rate

In the glucose analog method for determining local glucose utilization rates, time courses of tissue and plasma radioactivity are measured and then analyzed in terms of first-order exchange of label between tissue compartments. The rate of glucose utilization is assumed to have a fixed, linear relationship to the analog phosphorylation rate calculated from the fitted rate constants. Accurate estimation of the rate constants requires many hours of dynamic data acquisition. Therefore, techniques assuming a linear relationship between analog phosphorylation rate and total tissue concentration of label were developed to predict glucose utilization rates from a single scan. Previously reported linearizations differ in their sensitivity to differences between current and average kinetic rate constants, and thus in their accuracy. We have developed a method that is insensitive to the presumed value of the blood flow–capillary wall transport parameter k1. This new single-scan approach has been validated by comparison of the single-scan metabolic rate values with the values calculated from the dynamic measurements.

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A new in-situ method to determine the hydrolysis rate constant of adenosine triphosphate (ATP) by application of Raman spectroscopy in a hydrothermal diamond anvil cell

10.5194/egusphere-egu21-3419 ◽

2021 ◽

Author(s):

Christoph Moeller ◽

Christian Schmidt ◽

Francois Guyot ◽

Max Wilke

Keyword(s):

Adenosine Triphosphate ◽

Rate Constant ◽

Rate Constants ◽

Diamond Anvil Cell ◽

Elevated Temperatures ◽

Hydrolysis Rate ◽

Extreme Conditions ◽

Hydrolysis Rate Constant ◽

Diamond Anvil

In recent decades increasing evidence was found for life under extreme conditions, e.g., near black smokers on the ocean floor. The synthesis and stability of vital molecules like adenosine triphosphate (ATP) and adenosine diphosphate (ADP) are essential to maintain the metabolism of all known organisms. The lifetime of these molecules in water is limited by the non-enzymatic hydrolysis reaction that becomes dominant at elevated temperatures. A better understanding of this mechanism will provide us insights of life at extreme conditions.Previous studies determined the hydrolysis rate constants of ATP for several compositions, temperatures and pressures using quench experiments and subsequent analysis. So far, it was not tested whether quench artefacts might have affected those results. Therefore, the current study was performed to develop a method to follow the reaction in-situ with a high sampling rate at elevated temperatures. A confocal micro-Raman spectrometer and a hydrothermal diamond anvil cell were used to perform experiments at elevated temperatures and vapour pressure. Spectra were obtained in the range of 660 cm-1 to 1157 cm-1 as a function of time. Different solutions of ATP and ADP were measured at 353 K, 373 K, and 393 K, at starting pH values of 3 and 7. First findings are consistent with previous studies and show that with decreasing pH value the hydrolysis rate increases. The data indicate hydrolysis rate constants in the magnitude of 10-3 s-1 by 393 K, 10-4 s-1 by 373 K and 10-5 s-1 by 353 K. These initial observations show that this technique produces reliable kinetic data on this reaction. It also provides much better sampling statistics than quench experiments.&#160;The high reaction rates suggest that a mechanism exists to regulate this reaction at higher temperatures, which is necessary to allow metabolism under extreme conditions. Moreover, it is commonly known that ATP interacts with various metal ions with different effects on the reaction rate. An application of this method would be the quantification of the hydrolysis rate constant in chemically more complex systems.

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Solvent effect as a criterion of solvolysis mechanism. Solvolysis of 3-acyl-1,3-diphenyltriazenes

Collection of Czechoslovak Chemical Communications ◽

10.1135/cccc19812091 ◽

1981 ◽

Vol 46 (9) ◽

pp. 2091-2103 ◽

Cited By ~ 2

Author(s):

Oldřich Pytela ◽

Petr Svoboda ◽

Miroslav Večeřa

Keyword(s):

Transition State ◽

Solvent Effect ◽

Mole Fraction ◽

Rate Constant ◽

Rate Constants ◽

Proton Donor ◽

Hydrolysis Rate ◽

Solvent Mixtures ◽

Solvent Dependence ◽

Hydrolysis Of

Solvent dependence of hydrolysis rate constants of 3-acetyl-1,3-diphenyltriazene (I) and 3-(N-methylcarbamoyl)-1,3-diphenyltriazene (II) has been followed in the solvent mixtures ethanol-water, methanol-water, dioxane-water, and formamide-water within the mole fraction x = 0.0 to 0.5 at 25, 35 and 45 °C. A criterion has been suggested, based on sign of change of logarithm of the observed rate constant in dependence on change of the solvent composition, for evaluation of the reaction molecularity and, hence, participation of water in the hydrolysis mechanism. It has been found that water takes part as a proton donor in the transition state of hydrolysis of the substrates studied.

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Effect of Ischemia on Quantification of Local Cerebral Glucose Metabolic Rate in Man

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/jcbfm.1981.5 ◽

1981 ◽

Vol 1 (1) ◽

pp. 37-51 ◽

Cited By ~ 136

Author(s):

Randall A. Hawkins ◽

Michael E. Phelps> ◽

Sung-Cheng Huang ◽

David E. Kuhl

Keyword(s):

Glucose Metabolism ◽

Metabolic Rate ◽

Rate Constants ◽

Normal Values ◽

Cerebral Glucose Metabolism ◽

Stroke Rate ◽

Metabolic Rates ◽

Lumped Constant ◽

Glucose Metabolic Rate ◽

The Stability

The model for quantifying local cerebral glucose metabolic rates originally developed by Sokoloff et al. and modified by Phelps, Huang and co-workers was applied to humans with cerebral ischemia (i.e., stroke). Rate constants for fluorodeoxyglucose were measured in ischemic and nonischemic regions with positron computed tomography. Using measured rate constants for ischemia, the model generates more accurate estimates of local cerebral glucose metabolism as compared to the use of rate constants from normal young adults, because the local metabolic rate is significantly underestimated, and temporal instability of the model is observed when normal values are applied to ischemic regions. A method was also developed to test the stability of the local lumped constant. The estimates of the lumped constant showed no or only small variations between ischemic and nonischemic types. Thus, errors introduced in the calculated local cerebral glucose metabolism by inappropriate rate constants appear to be more significant than those caused by any potential change in the lumped constant in ischemia.

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Determination of rate constants of redox reactions of second order from current-less potential-time curves by a simplified graphical-numerical method

Collection of Czechoslovak Chemical Communications ◽

10.1135/cccc19831358 ◽

1983 ◽

Vol 48 (5) ◽

pp. 1358-1367 ◽

Cited By ~ 4

Author(s):

Antonín Tockstein ◽

František Skopal

Keyword(s):

Numerical Method ◽

Explicit Form ◽

Rate Constant ◽

Optimization Algorithm ◽

Rate Constants ◽

Redox Reactions ◽

Second Order ◽

Wide Region ◽

Recurrent Formula

A method for constructing curves is proposed that are linear in a wide region and from whose slopes it is possible to determine the rate constant, if a parameter, θ, is calculated numerically from a rapidly converging recurrent formula or from its explicit form. The values of rate constants and parameter θ thus simply found are compared with those found by an optimization algorithm on a computer; the deviations do not exceed ±10%.

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The Effect of p-Toluidine on the Two-Step Electroreduction of Zn(II) in Water-Methanol and Water-Dimethylformamide

Collection of Czechoslovak Chemical Communications ◽

10.1135/cccc19990585 ◽

1999 ◽

Vol 64 (4) ◽

pp. 585-594 ◽

Cited By ~ 2

Author(s):

Barbara Marczewska

Keyword(s):

Electron Transfer ◽

Binary Mixtures ◽

Rate Constant ◽

Rate Constants ◽

Electrode Surface ◽

Mercury Electrode ◽

Forward Rate ◽

Solvent Molecules ◽

Activated Complex

The acceleration effect of p-toluidine on the electroreduction of Zn(II) on the mercury electrode surface in binary mixtures water-methanol and water-dimethylformamide is discussed. The obtained apparent and true forward rate constants of Zn(II) reduction indicate that the rate constant of the first electron transfer increases in the presence of p-toluidine. The acceleration effect may probably be accounted for by the concept of the formation on the mercury electrode an activated complex, presumably composed of p-toluidine and solvent molecules.

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Radiolysis studies on the corrosion inhibitors 1 -hexyn-3-ol, cinnamonitrile, and 1,3-diethyl-2-thiourea

Canadian Journal of Chemistry ◽

10.1139/v95-264 ◽

1995 ◽

Vol 73 (12) ◽

pp. 2137-2142 ◽

Cited By ~ 1

Author(s):

A.J. Elliot ◽

M.P. Chenier ◽

D.C. Ouellette

Keyword(s):

Hydrogen Atom ◽

Hydroxyl Radical ◽

Temperature Dependence ◽

Rate Constant ◽

Rate Constants ◽

Corrosion Inhibitors ◽

Hydrated Electron

In this publication we report: (i) the rate constants for reaction of the hydrated electron with 1-hexyn-3-ol ((8.6 ± 0.3) × 108 dm3 mol−1 s−1 at 18 °C), cinnamonitrile ((2.3 ± 0.2) × 1010 dm3 mol−1 s−1 at 20 °C), and 1,3-diethyl-2-thiourea ((3.5 ± 0.3) × 108 dm3 mol−1 s−1 at 22 °C). For cinnamonitrile and diethylthiourea, the temperature dependence up to 200 °C and 150 °C, respectively, is also reported; (ii) the rate constants for the reaction of the hydroxyl radical with 1-hexyn-3-ol ((5.5 ± 0.5) × 109 dm3 mol−1 s−1 at 20 °C), cinnamonitrile ((9.2 ± 0.3) × 109 dm3 mol−1 s−1 at 21 °C), and diethylthiourea ((8.0 ± 0.8) × 108 dm3 mol−1 s−1 at 22 °C). For cinnamonitrile, the temperature dependence up to 200 °C is also reported; (iii) the rate constant for the hydrogen atom reacting with 1-hexyn-3-ol ((4.3 ± 0.4) × 109 dm3 mol−1 s−1 at 20 °C). Keywords: radiolysis, corrosion inhibitors, rate constants.

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