Validation of a model for [1-11C]acetate as a tracer of cardiac oxidative metabolism
| Autor: | H. R. Schelbert, Sung-Cheng Huang, C. K. Ng, D. B. Buxton |
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| Rok vydání: | 1994 |
| Předmět: |
Male
Physiology Citric Acid Cycle Kinetics Myocardial Ischemia Oxidative phosphorylation Acetates Rats Sprague-Dawley Oxygen Consumption Reference Values Physiology (medical) medicine Animals Tissue Distribution Carbon Radioisotopes Amino Acids Total Tissue Chromatography medicine.diagnostic_test Chemistry Myocardium Models Cardiovascular Glutamate receptor Rats Metabolic pathway Biochemistry Evaluation Studies as Topic Positron emission tomography Cardiology and Cardiovascular Medicine Flux (metabolism) Perfusion |
| Zdroj: | American Journal of Physiology-Heart and Circulatory Physiology. 266:H1304-H1315 |
| ISSN: | 1522-1539 0363-6135 |
| Popis: | To develop a compartmental model for estimating myocardial oxygen consumption rate (MVO2) with [1-11C]acetate, the metabolic fate of radiolabeled acetate was determined in normoxic and ischemic conditions in isolated perfused rat hearts. Glutamate composed 63 +/- 1 and 44 +/- 7% of the total tissue radioactivity 2 min postinjection in normoxic and ischemic myocardium, respectively, and radiolabeled glutamate remained the largest fraction throughout 40 min of perfusion. Based on the biochemical pathway of the tracer and the temporal distribution of 14C-labeled metabolites, a six-compartment model was formulated. Studies using [1-11C]acetate and a pair of NaI detectors were then performed in the same perfused heart system to validate the model. Consistency between the model predictions and biochemical measurements of tissue and effluent metabolites supported the validity of the kinetic model in normoxic and ischemic conditions. Model-estimated MVO2 correlated well with experimentally measured MVO2 for normoxic, hypoxic, and ischemic conditions, with a slope of 0.97 (r = 0.95). In addition, the model-estimated rate constant, k42, which corresponded to the oxidative flux, correlated strongly with the myocardial clearance rate (k1 or kmono) determined from the tissue kinetics. These findings provide a mechanistic basis for the use of k1 or kmono as an index of MVO2 in both normoxic and ischemic myocardium studied with [1-11C]acetate and positron emission tomography. |
| Databáze: | OpenAIRE |
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