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Regional myocardial oxygen consumption determined noninvasively in humans with [1-11C]acetate and dynamic positron tomography.

Experimental studies of animals have previously demonstrated the validity of [1-11C]acetate as a tracer of oxidative metabolism for use with positron emission tomography. The present study was undertaken to define in normal human volunteers the relation between myocardial clearance kinetics of [1-11C]acetate, and the rate-pressure product as an index of myocardial oxygen consumption. Twenty-two studies were performed of 12 volunteers. The rate-pressure product was increased with continuous supine bicycle exercise in six studies. Of the 16 resting studies, seven were performed in the fasted state and nine following an oral glucose load, to define possible effects of substrate availability on the tracer-tissue kinetics. Myocardial tissue time-activity curves were biexponential. Clearance of activity was homogeneous throughout the myocardium. The rate constants k1, obtained from biexponential fitting, and kmono, obtained by monoexponential fitting of the initial linear portion of the time-activity curves, correlated well with the rate-pressure product. Although the correlation coefficient was higher for k1 than for kmono (0.95 vs. 0.91), analysis on a sectorial basis showed less regional variability in kmono. This suggests that kmono, which is more practical than k1 because it requires shorter acquisition times, may be more clinically and experimentally useful for detection of myocardial segments with abnormal oxygen consumption. Overall, changes in myocardial substrate supply were without significant effect on the relation between the rate constants (k1 and kmono) and the rate-pressure product, although a small decrease in kmono/rate-pressure product was observed following oral glucose by paired analysis in four subjects. It is concluded that [1-11C]acetate can be used for the noninvasive measurement of myocardial oxygen consumption in humans with positron emission tomography, and, thus, has clinical and experimental potential as a tool for the understanding and diagnosis of myocardial disease.

Acetates↗

Oxygen consumption by chick embryos exposed to mechanical (shaking) stress.

Stage 34 (8-day) and 41 (15-day) chick embryos (Gallus gallus; in ovo) were exposed (3 min) to two separate amounts of mechanical (shaking) stress. Oxygen consumption determinations, following a temperature equilibration period (60 min), were made on entire, intact eggs using a Warburg apparatus equipped with 130-ml flasks modified to hold the egg. Shaking at 300 excursions per minute (epm) resulted in depressed O2 consumption by stages 34 and 41. Only stage 34 embryos had markedly depressed O2 consumption values when shaken at 100 epm. When exposed to 300 epm and reincubated for either 1, 2, or 4 hr prior to O2 consumption determinations stage 34 embryos, following an early return to control levels exhibited a marked fall in O2 consumption by 4 h reincubation. The stage 41 embryos, on the other hand, demonstrated a gradual rise to control O2 consumption levels by 4 h reincubation. Oxygen consumption has now been shown for the first time in an embryonic system (at two distinct developmental stages) to be functionally impaired by mechanically induced stress.

Animals↗

Induction of the ATP-dependent proteolytic system in guinea pig reticulocyte lysates by triiodothyronine.

The mechanism involved in the decreased numbers of several trans-membrane proteins such as sodium pump sites, sodium-lithium countertransport, sodium potassium cotransport proteins, proteins mediating the passive efflux of sodium and insulin receptors in erythrocytes from patients with hyperthyroidism is not known. The ATP-dependent proteolytic system which is involved in the loss of trans-membrane proteins during the maturation of the reticulocyte may be involved in the accelerated loss of these membrane proteins. Therefore, the effect of thyroid hormones on the ATP-dependent proteolytic activity of reticulocyte lysates was examined in this study. Reticulocytosis was induced in 14 guinea pigs by phenylhydrazine hydrochloride injections for 5 consecutive days followed by 2 days of rest. T3 (10 micrograms/100 g body weight) was injected into 7 animals on day 4 and day 6. Reticulocyte-rich blood was withdrawn on day 8. Oxygen consumption determined 24 hours after injection of T3 was 25% higher (p less than 0.01) and T3 treated animals had a 2.5 fold higher (p less than 0.01) weight loss than control animals. The ATP-dependent proteolytic activity measured in reticulocyte lysates using 125I labelled lysozyme was 3.6 fold higher in the T3 than in the control group of guinea pigs (p less than 0.01). We conclude that thyroid hormones induce the ATP-dependent proteolytic activity of reticulocyte lysates which may be responsible for the reduced number of several trans-membrane proteins found in erythrocytes from patients with hyperthyroidism.

Adenosine Triphosphate↗

Ouabain-binding sites of reticulocytes from guinea pigs treated with triiodothyronine.

To understand the mechanism of reduced number of sodium pump units (ouabain-binding sites, OBS) of erythrocytes in hyperthyroidism, OBS of reticulocytes from guinea pigs injected with triiodothyronine (T3) were measured. Reticulocytosis was induced in 16 guinea pigs by withdrawing 6 to 10 mL of blood for 5 days followed by 2 days rest. T3 (50 micrograms/100 g body weight) was injected into seven animals on days 4 and 6, and the remainder were injected with solvent for T3. Reticulocyte-rich blood was withdrawn on day 8. Oxygen consumption determined 24 hours after the first injection of T3 was 30% higher in the T3-treated animals (P less than .001). OBS of reticulocytes from control animals were sixfold higher than that of mature erythrocytes. Reticulocytes from T3-treated guinea pigs had significantly lower OBS (P less than .01) compared with controls. We conclude that the loss of OBS induced by thyroid hormones probably occurs during the formation of reticulocytes.

Animals↗

6-Hydroxydopamine and excitotoxin lesions of medial prefrontal cortex fail to affect schedule-induced drinking in the rat.

Schedule-induced drinking was examined in rats following 6-hydroxydopamine and N-methyl-D-aspartate lesions of the medial prefrontal cortex. 6-Hydroxydopamine reduced the concentrations of dopamine and noradrenaline in the medial prefrontal cortex to 17 and 37% of control values respectively, while changes were not observed in the nucleus accumbens. Lesions with N-methyl-D-aspartate were confined to the medial prefrontal cortex. Schedule-induced water consumption, determined over 11 consecutive 1 h/day testing sessions, was not significantly altered by either lesion. These results suggest that the mesocortical dopaminergic projection to the medial prefrontal cortex, and reciprocal projections from medial prefrontal cortex to the nucleus accumbens and the ventral tegmental area, are not essential for the acquisition of schedule-induced drinking.

Animals↗

Thyroid hormone action: early calorigenic effect on dispersed rat liver cells in the absence of protein synthesis.

Isolated dispersed rat liver cells were prepared by hypothyroid Sprague-Dawley rats. The cells were incubated under 95% O2/5% CO2 in Krebs-Ringer-bicarbonate buffer at pH 7.3-7.4 at 37 degrees C. The medium had been enriched with 2% bovine serum albumin (previously stripped of thyroid hormone) and 5-10 mM alanine as substrate. Two hour incubations were carried out with or without added triiodothyronine (T3) at 3 nM or 300-1,000 nM concentrations. Oxygen consumption determined at the end of the period of incubation with the Clark oxygen electrode showed stimulation above control values in the hormone treated flasks; parallel studies in which cycloheximide (100 microM) had been added to cells to block protein synthesis also showed enhanced oxygen consumption in response to T3. The results indicated a response to the hormone not dependent on new protein formation.

Animals↗

Calorigenic response in obese and nonobese women.

The calorigenic response to a high protein test meal was studied in women with a history of childhood onset obesity. Obese and nonobese individuals were fasted overnight and basal oxygen consumptions determined the following morning. A semisynthetic 823 kcal high protein test meal was ingested within a 1-hr period followed by hourly determinations of oxygen consumption and plasma levels of insulin, free fatty acids, triglycerides, glucose, amino acids, and urea nitrogen. Amino acid levels increased faster and to a higher plateau in the nonobese group, while insulin levels increased and eventually decreased in a similar fashion in both groups. No differences in basal metabolic rate were detected. The postprandial increment in oxygen consumption was significantly less among the obese subjects. Diminished calorigenesis after each meal would result in accumulation of extra calories provided that caloric consumption is not appropriately decreased. These data suggest that a physiological aberration of energy metabolism may contribute to the development of childhood onset obesity.

Adult↗

Neuropsychological performance and treatment outcome in male alcoholics.

Commonly used neuropsychological tests were administered to 91 detoxified alcoholics at the beginning of treatment. Statistically significant relationships were observed between test scores and post-treatment consumption determined 8 months after completing treatment for 72 patients. The results varied depending upon the particular measure of posttreatment consumption evaluated and the type of statistical analysis used. The most consistent relationships were often counter to the notion that increased neuropsychological performance is correlated with a more favorable treatment outcome. Neuropsychological evaluation is of limited clinical utility in predicting posttreatment alcohol consumption.

Adult↗

Myoglobin function in the isolated fluorocarbon-perfused dog heart.

An isolated dog heart preparation perfused with hemoglobin-free fluorocarbon suspension has been developed to study the role of myoglobin in myocardial function. The coronary vasculature was perfused at constant flow, with oxygen consumption determined from arteriovenous PO2 differences. Muscle function was assessed by measurement of pressures generated in a latex balloon placed in the left ventricle. The perfusate consisted of 20% perfluorotributylamine and 80% Ringer's lactate with 16 mM glucose. Steady-state oxygen consumption decreased from 0.30 to 0.11 ml/min per gram dry weight left ventricle, as perfusate PO2 decreased from 690 to 150 mmHg. Left ventricular pressure generation and oxygen consumption were determined before and after addition of 8 mM sodium nitrite, which changed functional ferrous myoglobin to high-spin ferric myoglobin. Over the range of perfusate PO2 studied, nitrite addition did not alter mechanical performance or myocardial oxygen consumption. These data suggest that those conditions necessary for substantial myoglobin-facilitated diffusion of oxygen in the myocardium are not present in the isolated fluorocarbon-perfused dog heart.

Animals↗

Does the severity of leukoaraiosis contribute to senile dementia? A comparative computerized and positron emission tomographic study.

The present study evaluates the origin, severity and location of leukoaraiosis in senile dementia and in normal ageing. The regional white-matter lucency scores, determined on computed-tomographic scan of the brain, are compared to the regional blood flow, oxygen extraction rate and oxygen consumption, determined by the [15O] steady-state technique with positron emission tomography. Thirty patients, classified according to the presence or absence of leukoaraiosis and their mental status, are examined. The occurrence and severity of dementia appear to be mainly correlated to decreased blood flow and oxygen metabolism in the frontal, temporal and parietal cerebral cortex. Leukoaraiosis in demented and nondemented patients is associated with lowered blood flow in the frontal and parietal white matter. The regional lucency score is increased, and blood flow and oxygen consumption decreased in the frontal white matter of severely demented patients. Frontal leukoaraiosis contributes to dementia and is probably of ischemic origin, while parietal and occipital leukoaraiosis is due to wallerian degeneration.

Aged↗

The actions of secretagogues on oxygen uptake by isolated mammalian parietal cells.

The action of histamine, carbamylcholine, and gastrin on oxygen uptake by cells isolated from canine fundic mucosa was studied in vitro. Viable mucosal cells were prepared by exposure of separated mucosa sequentially to collagenase and EDTA. Oxygen consumption, determined by polarography, was chosen as an index of physiological response of mucosal cells to secretagogues. Isobutyl methyl xanthine (IMX), carbamylcholine, histamine, and gastrín each independently stimulated oxygen uptake by the unfractionated mucosal cells. The response to histamine was greatly enhanced when IMX was present. In fractions of varying parietal cell content obtained with the Beckman elutriator rotor, basal and stimulated oxygen uptake correlated with the parietal cell content of the fractions. The percentage increases in oxygen uptake in response to histamine, gastrin, carbamylcholine, and IMX were similar in enriched fractions with from 50 to 85% parietal cells and in unenriched starting fractions. The normalized dose-response relations for histamine with an IMX background and for carbamylcholine were also similar in these two fractions.The specificity of these responses was tested by use of an H(2)-histamine receptor antagonist, metiamide, and an anticholinergic agent, atropine. At the doses used, neither metiamide (0.1 mM) nor atropine (10 muM) inhibited basal oxygen uptake. Histamine, studied with an IMX background, was inhibited by metiamide but not by atropine, while carbamylcholine was inhibited by atropine but not by metiamide. Neither metiamide nor atropine inhibited gastrin-stimulated oxygen uptake. These data indicate that in this in vitro system parietal cells account for most of the increase in oxygen uptake produced by exposure to gastric secretagogues and that histamine, gastrin, and carbamylcholine each independently stimulate oxygen uptake by the parietal cell. The specificity displayed by atropine and metiamide in this in vitro system suggests that the parietal cell has specific receptors for each of these secretagogues.

Animals↗

Conditioning program for competitive figure skating.

To test the feasibility that traditional interval training methods could be adapted to the needs of competitive figure skaters, an interval skating program was conducted during a 3-month period for a group of skaters at diverse levels of proficiency. The program required only a small portion of the total ice time utilized by the skaters on a daily basis, i.e., 1/2 hr, three times a week. On alternate days, the skaters used the same amount of time in a strength training program. A flexibility-stretching facet was to be done by the skaters on a daily basis. Progress was evaluated by treadmill oxygen consumption determinations and ability to perform a 1/2-mile skate effort. Over the course of the 3-month period, the skaters in the program showed an average increase in oxygen consumption of 9% from 44.73 cc per kg per min to 55.51 cc per kg per min. This was accompanied by an average 10-sec reduction in the timed effort at the 1/2-mile skate. Subjectively, the skaters were less fatigued during their freestyle skating programs and were able to improve consistency at skilled maneuvers in the last minute of their performances. This initial effort to evaluate the efficacy of this type of a training program for competitive figure skating seems to have proven to be beneficial to the skaters. Currently, we are continuing our efforts to expand the program.

Adolescent↗

Arm exercise testing with myocardial scintigraphy in asymptomatic patients with peripheral vascular disease.

Arm exercise with myocardial scintigraphy and oxygen consumption determinations was performed by 33 men with peripheral vascular disease, 40 to 74 years of age (group 2). None had evidence of coronary disease. Nineteen age-matched male control subjects (group 1) were also tested to determine the normal endurance and oxygen consumption during arm exercise in their age group and to compare the results with those obtained during a standard treadmill performance. The maximal heart rate, systolic blood pressure, pressure rate product, and oxygen consumption were all significantly lower for arm than for leg exercise. However, there was good correlation between all these parameters for both types of exertion. The maximal heart rate, work load and oxygen consumption were greater for group 1 subjects than in patients with peripheral vascular disease despite similar activity status. None of the group 1 subjects had abnormal arm exercise ECGs, while six members of group 2 had ST segment changes. Thallium-201 scintigraphy performed in the latter group demonstrated perfusion defects in 25 patients. After nine to 29 months of follow-up, three patients who had abnormal tests developed angina and one of them required coronary bypass surgery. Arm exercise with myocardial scintigraphy may be an effective method of detecting occult ischemia in patients with peripheral vascular disease. Those with good exercise tolerance and no electrocardiographic changes or 201T1 defects are probably at lower risk for the development of cardiac complications, while those who develop abnormalities at low exercise levels may be candidates for invasive studies.

Adult↗

Dynamic characteristics of a metabolic reaction of mice with different responses to irradiation.

The course of the reaction of mice placed in a metabolic chamber and afterwards irradiated with an exposure dose of 610 R was studied by assessing total oxygen consumption and the size of its fluctuation. Fluctuation was greater in non-survivors than in survivors in the initial phase of the metabolic reaction only (P is less than 0.05), while the mean oxygen consumption values for the two groups were the same, In the distribution of the individual values there were more non-survivors in the frequency class with a high fluctuation level and, conversely, more survivors in the low level class (P is less than 0.01). Fluctuation during the studied reaction was more variable in survivors, despite its lower level, than in non-survivors. The reciprocal relationship between the size and fluctuation of oxygen consumption, determined for the whole series of experimental mice at given stages of the metabolic reaction, is linear. Attention is drawn to the association between changes measured in the metabolic rate and motor activity and to the possibility that it is determined by the individual's type of nervous activity.

Animals↗