Effects of substrate availability on myocardial C-11 palmitate kinetics by positron emission tomography in normal subjects and patients with ventricular dysfunction.
Effects of substrate availability on myocardial C-11 palmitate kinetics by positron emission tomography in normal subjects and patients with ventricular dysfunction.
复制标题
通过正电子发射断层扫描在正常受试者和心室功能不全患者中底物可用性对心肌 C-11 棕榈酸酯动力学的影响。
DOI：
10.1016/0002-8703(86)90006-2
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发表时间：
1986
影响因子：
4.8
通讯作者：
Phelps,ME
中科院分区：
文献类型：
--
作者：
Schelbert,HR;Henze,E;Sochor,H;Grossman,RG;Huang,SC;Barrio,JR;Schwaiger,M;Phelps,ME
在5名正常志愿者和16名心室功能不全患者中，对C-11棕榈酸酯和正电子发射断层扫描（PET）在正常和患病人体心肌中心肌底物代谢变化的可能性进行了检查，以响应血液中底物可用性的改变和疾病相关的异常。在禁食过夜后（对照期）和口服葡萄糖（50 gm）后2小时再次进行C-11棕榈酸酯注射和系列PET成像。心肌C-11的时间-活性曲线从系列PET图像显示双指数清除模式。由相对大小和清除半衰期定义的早期快速相反映了内源性脂质池中的C-11棕榈酸氧化和晚期缓慢相示踪剂沉积。在对照期间，正常受试者进入早期快速相的示踪剂分数平均为47 ± 13%（SD），患者为45 ± 12%。相应的清除半衰期分别为19 ± 7和20 ± 5分钟。血糖后心率和血压保持不变，但血糖水平在正常人中上升了72.5%，在患者中上升了98.9%，而游离脂肪酸水平分别下降了72%和42%（p< 0.001）。在正常人中，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棕榈酸组织动力学对葡萄糖的反应是可变的。在9例患者中，它类似于在正常人，而在其他7例患者的“矛盾”的反应发生。葡萄糖给药后，进入快速清除期的示踪剂分数增加30%（p< 0.05），清除半衰期下降36%（p< 0.05）。反常反应与疾病病因或血浆底物水平无关，但主要发生在左心室，功能更严重抑制。因此，PET和C-11棕榈酸酯允许非侵入性地证明已知的人类心脏底物代谢对改变的底物可用性的反应。空腹人体葡萄糖给药可作为底物调节的激发试验，其在心肌疾病中可能异常，并且可以无创性证明。
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< 0.001), respectively. In normal subjects, the tracer fraction in the early rapid phase fell by 43% (p< 0.005) and the clearance half-time increased by 46% (p< 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< 0.05) associated with a 36% (p< 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.