GLUCOSE-UPTAKE AND LUMPED CONSTANT VARIABILITY IN NORMAL HUMAN HEARTSDETERMINED WITH [F-18] FLUORODEOXYGLUCOSE

Background. Myocardial glucose uptake can be measured with [F-18]fluor o-2-deoxyglucose (FDG) and positron emission tomography (PET). However , changes of myocardial metabolism may alter the ratio between the net rates of FDG and glucose uptake, known as the lumped constant. We tes ted the hypothesis that the variability of the lumped constant determi ned in animals explains the disagreement between human net myocardial glucose uptake calculated from aortocoronary sinus deficits and measur ed with PET. Methods and Results. In the three-compartment model of gl ucose transfer into cells, the lumped constant is a function of the re lationship between the net and the unidirectional rates of uptake of g lucose and glucose tracers such as FDG. Using this principle, validate d in the human brain and the animal heart under experimental condition s, we estimated the lumped constant of the human heart by PET in 10 he althy men under several metabolic conditions established by altering t he circulating insulin level during a euglycemic clamp and with somato statin and heparin infusions, The lumped constant varied systematicall y between 0.44 and 1.35. At insulin levels below 100 pmol/L, free fatt y acids were inversely related to serum insulin levels and the lumped constant increased linearly with serum insulin concentration. At insul in levels above 100 pmol/L, free fatty acids were suppressed and the l umped constant varied in inverse proportion to the insulin level. When the lumped constant was estimated in this manner, net myocardial gluc ose uptake agreed with that determined in previous measurements of blo od flow and aortocoronary sinus deficit. Conclusion. In the intact hum an organism, the cardiac lumped constant varies with the metabolic con dition, as predicted from studies of the brain and animal heart under experimental conditions.