Effects of substrate availability on myocardial C-11 palmitate kinetics by positron emission tomography in normal subjects and patients with ventricular dysfunction

• Published in: The American heart journal Vol. 111; no. 6; pp. 1055 - 1064
• Main Authors: Schelbert, Heinrich R., Henze, Eberhard, Sochor, Heinz, Grossman, Robert G., Huang, Sung-Cheng, Barrio, Jorge R., Schwaiger, Markus, Phelps, Michael E.
• Format: Journal Article
• Language: English
• Published: New York, NY Mosby, Inc 01.06.1986; Elsevier
• Subjects: Adult; Biological and medical sciences; Blood Glucose - metabolism; Carbon Radioisotopes; Cardiology. Vascular system; Fatty Acids, Nonesterified - blood; Female; Heart; Heart Diseases - metabolism; Heart Diseases - physiopathology; Heart failure, cardiogenic pulmonary edema, cardiac enlargement; Hemodynamics; Humans; Kinetics; Male; Medical sciences; Metabolic Clearance Rate; Middle Aged; Myocardium - metabolism; Palmitates - metabolism; Palmitic Acids - metabolism; Tomography, Emission-Computed; Radionuclide study; Human; Heart disease; Oral administration; Myocardium; Cardiovascular disease; Lipids; Glucose; Left ventricular failure; Metabolism; Positron emission tomography
• ISSN: 0002-8703; 1097-6744
• 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 < 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.