To clarify the metabolic fate of radioiodinated heptadecanoic acid in myocardium, the time course and distribution of the radioactivity over '311-heptadecanoic acid, free radioiodide, and various lipids (with incorporated iodoheptadecanoic acid) were determined in normal canine myocardium. In 10 dogs seven biopsy specimens were taken over 30 min after injection of 1311-heptadecanoic acid. The radioactivity in the specimens increased until the fifth minute and decreased thereafter, with a half-time of 36 min. In the fifth minute, 61% of the radioactiviy was free iodide, and its curve paralleled the curve of the total radioactivity. As early as the first minute 13'I-heptadecanoic acid activity was reduced to 14% and decreased further. Activity of radioiodinated phospholipids, (mono, di, tri)-glycerides, and cholesterol-esters remained constant after an initial increase. These results indicate that immediately after uptake, '3'I-heptadecanoic acid is either metabolized, liberating the radioiodide, or stored in lipids. Because the activity of radiolabeled lipids remained constant during the study period and because iodide activity paralleled the total activity in biopsy specimens, it is concluded that in normal myocardium, washout of free radioiodide determines the elimination rate as observed during a scintigraphic study. Thus the elimination rate cannot be related to the ,8-oxidation rate as previously supposed. Circulation 72, No. 3, 565-71, 1985. THE HEART uses a variety of substances like glucose, free fatty acids, and lactate as an energy source for its metabolism. Under normal physiologic conditions, 60% to 80% of energy-rich phosphate bonds are derived from oxidation of long-chain free fatty acids.' Therefore long-chain free fatty acids labeled with a radioisotope were proposed as indicators of cardiac metabolism in vivo. One of these radiolabeled free fatty acids was heptadecanoic acid (HDA) labeled with 123I in the omega position.It was found that after administration of radiolabeled HDA, regional elimination of the radioactivity differed under various pathophysiologic conditions of the myocardium. In ischemic myocardium the elimination rate was found to be lower than that in comparable normal myocardium.A-"0 In some patients with a recently sustained infarction, a higher elimination rate Two hypotheses have been developed to explain the observed differences in elimination rates. Both hypotheses are related to cardiac metabolism of radioiodinated free fatty acids. After uptake in the myocyte, radioiodinated long-chain free fatty acids are degraded by /3-oxidation'4 in the mitochondria. Radioiodine is split off and leaves the cell.In the first hypothesis the elimination rate is related to the /-oxidation rate of the radioiodinated fatty acids'5 in the mitochondria. In the second hypothesis the elimination rate is related to the diffusion rate of radioiodide from the myocardial mitochondria into the systemic circulation. 6 Because knowledge of the underlying mechanism is important for interpretat...
To investigate the feasibility of radioiodinated free fatty acids for 'metabolic imaging', the kinetics and distribution pattern of metabolites of 131I-heptadecanoic acid were studied in canine myocardium throughout metabolic interventions. In control dogs and in dogs during glucose/insulin and sodium lactate infusion, biopsy specimens were taken during a 90-min period after 131I-HDA administration and analyzed. Clearly distinct patterns of distribution and elimination were seen during the metabolic interventions, indicating the usefulness of iodinated fatty acids for metabolic studies.
We studied the dependency of myocardial oxygen consumption on the mechanical events during left ventricular relaxation in isolated supported cat hearts. The volume of the left ventricle was controlled by means of a balloon connected to a membrane pump. Oxygen consumption (MVO2 in cm3.min-1.100 g-1) for three protocols (PROT) performed at peak isovolumic pressure, was studied: (1) rapid ejection to zero pressure, (2) partial rapid ejection followed by redevelopment of pressure, (3) volume expansion during relaxation, and compared with oxygen consumption of isovolumic (ISOV) beats. We found (mean +/- SD): (table; see text) In the protocols 1 and 3 the differences were not significant (paired Student's t-test, p greater than 0.05). In protocols 1 and 2 left ventricular volume was decreased up to 2.15 cm3 (i.e. stroke volume, SV) during the pressure release. We studied the specific effect of ejection (i.e., wall muscle shortening) in a fourth protocol in which the ventricle ejected up to 2.7 cm3 under nearly zero pressure load (isobaric contraction). There was a small amount of oxygen consumption associable with this unloaded ejection i.e. MVO2 = 3.38 (+/- 0.47) + 0.30 (+/- 0.16) SV, but it was too small to compensate for a decrease in MVO2 expected from the pressure release according to the tension time index. These findings suggest that oxygen consumption does not depend on the mechanical events during ventricular relaxation.
Under normal and ischemic conditions backdiffusion of radiolabeled non-esterified fatty acids (NEFA) has been demonstrated. In the fasted normal canine heart the extraction fraction (EF) during interventions with glucose or lactate loading, vasodilation, and metabolic level augmentation was determined, and compared with the control EF. Backdiffusion alterations were deduced from the EF changes. After iv injection of 17-iodo-131 heptadecanoic acid (IHDA), 11 blood samples were drawn from aorta and coronary sinus in a time period of 60 minutes. In the control and vasodilation group the EF slowly decreased from 40 to 10%. In contrast, the EF in the noradrenaline group was constant. During glucose and lactate infusion the EF became negative within 10 min and remained negative. These results suggest that during physiological circumstances backdiffusion is determined by the metabolic level of the heart and its substrate availability.
Radioiodinated free fatty acids have been developed to study myocardial metabolism non-invasively in man. In the present study the distribution of radiolabeled lipids in the myocardium and in arterial and coronary sinus blood was evaluated following injection of three commonly used iodinated fatty acids in fasted (n = 5) and lactate loaded (n = 3) dogs. Five minutes after simultaneous i.v. injection of radioiodinated 17-I-heptadecanoic acid (IHDA), 15-(p-I-phenyl) pentadecanoic acid (IPPA) and 15-(p-I-phenyl)-3,3-dimethyl-pentadecanoic acid (DMIPPA) a biopsy specimen and samples of arterial and coronary sinus blood were taken. After extraction and TLC the relative distribution of radioactivity in the aqueous phase (containing the oxidation products), pellet and organic phase was calculated. The organic phase was further divided into phospholipids, diglycerides, free fatty acids, triglycerides and cholesterol-esters. Seventy two percent of IHDA was oxidized, 36% of IPPA and 7% of DMIPPA. The organic phase consisted primarily of triglycerides and phospholipids. The ratios of triglycerides to phospholipids were about the same for IHDA, IPPA and DMIPPA (0.58, 0.65 and 0.50, respectively). Free IHDA in tissue samples was low (4%) and elevated for IPPA and DMIPPA, (17% and 37%). During lactate loading triglycerides were higher for all three fatty acids. For IHDA and IPPA this increase was paralleled by a decrease in the aqueous phase, in case of DMIPPA the aqueous phase remained the same. Five minutes after injection most of the organic phase of both arterial and coronary sinus blood consisted of the injected fatty acids, the aqueous phase contained oxidation products. There were only minor differences during lactate loading.(ABSTRACT TRUNCATED AT 250 WORDS)
Optimal fitting of a myocardial time-activity curve is accomplished with a monoexponential plus a constant, resulting in three parameters: amplitude and half-time of the monoexponential and the constant. The aim of this study was to estimate the precision of the calculated parameters. The variability of the parameter values as a function of the acquisition time was studied in 11 patients with cardiac complaints. Of the three parameters the half-time value varied most strongly with the acquisition time. An acquisition time of 80 min was needed to keep the standard deviation of the half-time value within ±10%. To estimate the standard deviation of the half-time value as a function of the parameter values, of the noise content of the time-activity curve and of the acquisition time, a model experiment was used. In most cases the SD decreased by 50% if the acquisition time was increased from 60 to 90 min. A low amplitude/constant ratio and a high half-time value result in a high SD of the half-time value. Tables are presented to estimate the SD in a particular case.
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