Glucose uptake and lumped constant variability in normal human hearts determined with [F-18]fluorodeoxyglucose

Glucose uptake and lumped constant variability in normal human hearts determined with [F-18]fluorodeoxyglucose
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DOI:
10.1016/s1071-3581(97)90061-1
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发表时间:
1997-03-01
影响因子:
2.4
通讯作者:
Gjedde, A
Gjedde, A
中科院分区:
医学3区
文献类型:
--
作者:
Botker, HE;Bottcher, M;Gjedde, A

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背景心肌葡萄糖摄取可以用[F-18]氟-2-脱氧葡萄糖(FDG)和正电子发射断层扫描(PET)测量。然而,心肌代谢的变化可能会改变FDG和葡萄糖摄取的净速率之间的比率,称为集总常数。我们测试的假设,在动物中确定的集总常数的变异性解释了人类净心肌葡萄糖摄取之间的分歧计算从冠状窦赤字和测量与PET.Methods和结果。在葡萄糖转移到细胞中的三室模型中,集总常数是葡萄糖和葡萄糖示踪剂(如FDG)的净摄取速率与单向摄取速率之间关系的函数。使用这一原则,在实验条件下,在人脑和动物心脏验证,我们估计的集总常数PET在10个健康的男性在几种代谢条件下,通过改变循环胰岛素水平在正葡萄糖钳夹和生长抑素和肝素输注,集总常数在0.44和1.35之间系统地变化。当胰岛素水平低于100 pmol/L时,游离脂肪酸与血清胰岛素水平呈负相关,且集总常数随血清胰岛素浓度线性增加。当胰岛素水平高于100 pmol/L时,游离脂肪酸被抑制,并且集总常数与胰岛素水平成反比变化。当以这种方式估计集总常数时,心肌葡萄糖净摄取与以前测量血流量和冠状窦功能不全时的结果一致。在完整的人体组织中,心脏集中常数随代谢条件而变化,正如在实验条件下对大脑和动物心脏的研究所预测的那样。
Background. Myocardial glucose uptake can be measured with [F-18]fluoro-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 tested the hypothesis that the variability of the lumped constant determined in animals explains the disagreement between human net myocardial glucose uptake calculated from aortocoronary sinus deficits and measured with PET.Methods and Results. In the three-compartment model of glucose transfer into cells, the lumped constant is a function of the relationship between the net and the unidirectional rates of uptake of glucose and glucose tracers such as FDG. Using this principle, validated in the human brain and the animal heart under experimental conditions, we estimated the lumped constant of the human heart by PET in 10 healthy men under several metabolic conditions established by altering the circulating insulin level during a euglycemic clamp and with somatostatin and heparin infusions, The lumped constant varied systematically between 0.44 and 1.35. At insulin levels below 100 pmol/L, free fatty acids were inversely related to serum insulin levels and the lumped constant increased linearly with serum insulin concentration. At insulin levels above 100 pmol/L, free fatty acids were suppressed and the lumped constant varied in inverse proportion to the insulin level. When the lumped constant was estimated in this manner, net myocardial glucose uptake agreed with that determined in previous measurements of blood flow and aortocoronary sinus deficit.Conclusion. In the intact human organism, the cardiac lumped constant varies with the metabolic condition, as predicted from studies of the brain and animal heart under experimental conditions.