Regional myocardial free fatty acid extraction in normal and ischemic myocardium.

Abstract

The rate constant for free fatty acid influx (kl) was studied in normal and ischemic myocardium.In 15 normal subjects and 30 patients with coronary artery disease, 20MTl and 15-(p-_231-iodophenyl)-pentadecanoic acid (IPPA) were administered during exercise under fasting conditions and at rest. In 10 patients, the study was repeated after percutaneous transluminal coronary angioplasty; in three patients, the study was repeated after infarction. The initial accumulation of IPPA, related to that of 2`1TI (both background and crossover corrected), was used for determinations of the regional rate constant of IPPA influx into myocardial tissue (kl*). In normal subjects, no significant differences in kl* between major myocardial segments were found; the average value of kl* was 0.57 0. 13/min (mean + SD) at rest and 0.42 0.06/min at exercise (average workload, 123 47 W). With increasing free fatty acid plasma concentration and perfusion, free fatty acid influx increased in a saturable fashion. The Michaelis-Menten constant (KM*) and the maximal velocity (Vm.*) for IPPA influx into myocardial tissue were estimated to be 470 nmol/g and 430 nmol/g * min, respectively. In ischemic areas, k1* was reduced to 57±18 % of k1* value in nonaffected segments. The areas were larger than those showing reduced 201T1 uptake. Preinfarction and postinfarction studies showed that the size of 20`TI defects in postinfarction images corresponded with the size of the area with reduced kl* observed in preinfarction scintigrams. Revascularization led to an increase of 20`TI uptake and to normalization of kl*.

Fatty acid uptake in normal human myocardium.

“…The changes of f during the exercise were estimated on the basis of '01T1 uptake as described previously. 5 Determination of the FA concentration in plasma. For the determination of FA concentration in plasma, an enzymatic colorimetric method (NEFA C kit, Wako Chemicals, Neuss, FRG) was used.…”

Supportive Measures and Finer Practice Points in 177Lu-DOTATATE PRRT for NET: Aiming for Optimal Disease Management

“…Radioiodinated PPA was experimentally shown to have a metabolic pathway resembling that of palmitic acid. Most important, among various clinical applications iodophenylpentadecanoic acid was proven to normalize energy metabolism after revascularization (8). Furthermore, a modeling approach allows quantification, which may be useful in other therapeutic strategies (9).…”

Myocardial substrate metabolism in obesity

“…This has also been demonstrated in other cardiovascular disorders such a hypertensive heart disease and diabetes. 24,25 Using 31 P magnetic resonance spectroscopy, cardiac energetics can be assessed by quantifying the relative concentrations of phosphocreatine (PCr) and ATP in the myocardium to derive the PCr/ATP ratio, a sensitive index of the energetic state of the heart. In heart failure, the PCr/ ATP ratio correlates with LV function 26 and clinical status, 27 and has been shown to be a better prognostic indicator than LV ejection fraction.…”

“…21 The importance is again highlighted in the setting of heart failure and left ventricular (LV) hypertrophy, where mitochondrial oxidative capacity is reduced and metabolism shifts back towards a reliance on glucose metabolism, resembling the fetal metabolic program. 22,23 As the heart is an extremely efficient scavenger of circulating non-esterified FFAs (up to 40% extraction fraction), 24 the rate of fatty-acid uptake by the heart is primarily determined by the concentration of non-esterified fatty acids in the plasma. 25 The concentration of serum FFAs is highly regulated and represents a balance between production via hormone-sensitive lipaseinduced adipose tissue triglyceride breakdown and synthesis via glycerolphosphate acyltransferase.…”