Schelbert H R, Henze E, Sochor H, Grossman R G, Huang S C, Barrio J R, Schwaiger M, Phelps M E
Am Heart J. 1986 Jun;111(6):1055-64. doi: 10.1016/0002-8703(86)90006-2.
The possibility of demonstrating noninvasively with C-11 palmitate and positron emission tomography (PET) changes in myocardial substrate metabolism in normal and diseased human myocardium in response to altered substrate availability in blood and disease-related abnormalities was examined in five normal volunteers and 16 patients with ventricular dysfunction. C-11 palmitate injection and serial PET imaging were performed after an overnight fast (control period) and again 2 hours later after oral glucose (50 gm). Myocardial C-11 time-activity curves from serial PET images revealed a biexponential clearance pattern. An early rapid phase, defined by relative size and clearance half-time, reflects C-11 palmitate oxidation and the late slow phase tracer deposition in the endogenous lipid pool. During the control period, the tracer fraction entering the early rapid phase averaged 47 +/- 13% (SD) in normal subjects and 45 +/- 12% in patients. Corresponding clearance half-times were 19 +/- 7 and 20 +/- 5 minutes, respectively. Heart rate and blood pressure remained unchanged after glucose, but plasma glucose levels rose by 72.5% in normal subjects and by 98.9% in patients, while free fatty acid levels fell by 72% and 42% (p less than 0.001), respectively. In normal subjects, the tracer fraction in the early rapid phase fell by 43% (p less than 0.005) and the clearance half-time increased by 46% (p less than 0.01). In patients, the response of C-11 palmitate tissue kinetics to glucose was variable. In nine patients, it was similar to that in normal subjects while in the other seven patients a "paradoxic" response occurred. The tracer fraction entering the rapid clearance phase increased after glucose by 30% (p less than 0.05) associated with a 36% (p less than 0.05) decline in clearance half-times. The paradoxic response was unrelated to disease etiology or plasma substrate levels but occurred mostly in left ventricles with more severely depressed function. Thus, PET and C-11 palmitate allow the noninvasive demonstration of the known response of substrate metabolism of the human heart to altered substrate availability. Glucose administration in fasted humans serves as a provocative test of substrate regulation which can be abnormal in myocardial disease and can be demonstrated noninvasively.
我们利用C-11软脂酸盐和正电子发射断层扫描（PET）对5名正常志愿者和16名心室功能不全患者进行研究，以探讨能否通过非侵入性方法显示正常和患病人类心肌中，心肌底物代谢随血液中底物可用性改变及疾病相关异常情况而发生的变化。在禁食过夜（对照期）后，静脉注射C-11软脂酸盐并进行PET连续成像，2小时后口服葡萄糖（50克），再次进行PET连续成像。PET连续图像的心肌C-11时间-活性曲线显示出双指数清除模式。根据相对大小和清除半衰期定义的早期快速相反映了C-11软脂酸盐氧化，晚期缓慢相反映了示踪剂在内源性脂质池中的沉积。在对照期，正常受试者进入早期快速相的示踪剂分数平均为47±13%（标准差），患者为45±12%。相应的清除半衰期分别为19±7分钟和20±5分钟。口服葡萄糖后心率和血压保持不变，但正常受试者血浆葡萄糖水平升高72.5%，患者升高98.9%，而游离脂肪酸水平分别下降72%和42%（p<0.001）。在正常受试者中，早期快速相的示踪剂分数下降43%（p<0.005），清除半衰期增加46%（p<0.01）。在患者中，C-11软脂酸盐组织动力学对葡萄糖的反应存在差异。9名患者的反应与正常受试者相似，而另外7名患者出现“反常”反应。口服葡萄糖后，进入快速清除相的示踪剂分数增加30%（p<0.05），清除半衰期下降36%（p<0.05）。这种反常反应与疾病病因或血浆底物水平无关，但大多发生在功能严重受损的左心室。因此，PET和C-11软脂酸盐能够非侵入性地显示已知的人类心脏底物代谢对底物可用性改变的反应。禁食状态下给人类服用葡萄糖可作为一种底物调节激发试验，该试验在心肌疾病中可能异常，且可通过非侵入性方法显示。
