Investigation of the sup 18 F-2FDG/glucose lumped constant behavior in isolated working rat hearts
The behavior of the {sup 18}F-2FDG/Glucose lumped constant (LC) in heart was investigated using an improved isolated perfused working rat heart model, quantitative external counting of total tissue radioactivity by fast coincidence detection of positron-emitting radionuclides, and digital compartmental modeling of tracer kinetics. The ability of the 2FDG compartmental model to predict the time courses of the fractions of the total radioactivity attributable to 2FDG6-phosphate was biochemically validated for six perfusion conditions by directly assaying the 2FDG-6-phosphate fractions from acid extractions of freeze-clamped myocardial tissue. In {sup 14}C 2FDG recirculation experiments, chromatographic analyses indicated that the only two significant species in the myocardium were {sup 14}C 2FDG and {sup 14}C 2FDG-6phosphate. The use of 2-({sup 3}H)glucose for measuring glucose phosphorylation rates was also validated by correlating steady-state tritiated water production with enzymatic assay of glucose disappearance. From constant infusion experiments, the values of the LC were determined to be 0.942 {plus minus} 0.062, 0.770 {plus minus} 0.166, 1.191 {plus minus} 0.054, 0.685 {plus minus} 0.093, and 0.334 {plus minus} 0.026, for hearts perfused with 5 and 30 mM glucose without insulin, and 2, 3.5, and 5 mM glucose with insulin respectively. The monotonic decrease of the LC as glucose concentration is increased in the presence of insulin can be explained by the shift in control strength for glucose uptake between membrane transport and the phosphorylation reaction. Bolus injection experiments analyzed with compartmental models indicated the occurrence of the following sequence: limited glucose supply relative to metabolic demand; decreased cellular glucose content; increased importance of the transport process in the limitation of hexose uptake; increased value for the LC.
- Research Organization:
- Wisconsin Univ., Madison, WI (USA)
- OSTI ID:
- 5735143
- Resource Relation:
- Other Information: Thesis (Ph. D.)
- Country of Publication:
- United States
- Language:
- English
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GLUCOSE
METABOLISM
RADIOPHARMACEUTICALS
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL MODELS
FLUORINE 18
HEART
INSULIN
PERFUSED ORGANS
POSITRON COMPUTED TOMOGRAPHY
RATS
ALDEHYDES
ANIMALS
BETA DECAY RADIOISOTOPES
BETA-PLUS DECAY RADIOISOTOPES
BODY
CARBOHYDRATES
CARDIOVASCULAR SYSTEM
COMPUTERIZED TOMOGRAPHY
DIAGNOSTIC TECHNIQUES
DRUGS
EMISSION COMPUTED TOMOGRAPHY
FLUORINE ISOTOPES
HEXOSES
HORMONES
HOURS LIVING RADIOISOTOPES
ISOMERIC TRANSITION ISOTOPES
ISOTOPES
KINETICS
LABELLED COMPOUNDS
LIGHT NUCLEI
MAMMALS
MONOSACCHARIDES
NANOSEC LIVING RADIOISOTOPES
NUCLEI
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
ORGANS
PEPTIDE HORMONES
PROTEINS
RADIOISOTOPES
REACTION KINETICS
RODENTS
SACCHARIDES
TOMOGRAPHY
VERTEBRATES
550601* - Medicine- Unsealed Radionuclides in Diagnostics