In vivo measurement of myocardial protein turnover using an indicator dilution technique
Journal Article
·
· Circulation Research (An Official Journal of the American Heart Association); (USA)
- Yale Univ. School of Medicine, New Haven, CT (USA)
We applied a nondestructive tracer technique, previously developed for measuring skeletal muscle protein turnover, to the measurement of myocardial protein turnover in vivo. During a continuous infusion of L-(ring-2,6-3H)phenylalanine to anesthetized, overnight-fasted dogs, we measured the uptake of radiolabeled phenylalanine from plasma and the release of unlabeled phenylalanine from myocardial proteolysis using arterial and coronary sinus catheterization and analytic methods previously applied to skeletal muscle. Using these measurements, together with a model of myocardial protein synthesis that assumes rapid equilibration of tracer specific activity between myocardial phenylalanyl-tRNA and circulating phenylalanine, we estimated the rates of heart protein synthesis and degradation. The rate of heart protein synthesis was also estimated directly from the incorporation of labeled phenylalanine into tissue protein. The use of (3H)phenylalanine was compared with L-(1-14C)leucine in the measurement of heart protein turnover in dogs given simultaneous infusion of both tracers. Leucine uptake and release by the myocardium exceeded that of phenylalanine by 3.1 +/- 0.4- and 1.7 +/- 0.3-fold, respectively, consistent with leucine's 2.4-fold greater abundance in heart protein and its metabolism via other pathways. Phenylalanine is the preferred tracer for use with this method because of its limited metabolic fate in muscle. One theoretical limitation to the method, slow equilibration of circulating labeled phenylalanine with myocardial phenylalanyl-tRNA, was resolved by comparison of these specific activities after a 30-minute infusion of labeled phenylalanine in the rat. A second, empirical limitation involves precision in the measurement of the small decrements in phenylalanine specific activity that occur with each pass of blood through the coronary circulation.
- OSTI ID:
- 6283710
- Journal Information:
- Circulation Research (An Official Journal of the American Heart Association); (USA), Journal Name: Circulation Research (An Official Journal of the American Heart Association); (USA) Vol. 67:4; ISSN CIRUA; ISSN 0009-7330
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
550501* -- Metabolism-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
AMINO ACIDS
ANIMALS
BODY
CARBON 14 COMPOUNDS
CARBOXYLIC ACIDS
CARDIOVASCULAR SYSTEM
CHROMATOGRAPHY
DOGS
HEART
HYDROGEN COMPOUNDS
ISOTOPE APPLICATIONS
ISOTOPE DILUTION
LABELLED COMPOUNDS
LEUCINE
LIQUID COLUMN CHROMATOGRAPHY
MAMMALS
METABOLISM
MUSCLES
MYOCARDIUM
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANS
PHENYLALANINE
PROTEINS
SEPARATION PROCESSES
TRACER TECHNIQUES
TRITIUM COMPOUNDS
VERTEBRATES
59 BASIC BIOLOGICAL SCIENCES
AMINO ACIDS
ANIMALS
BODY
CARBON 14 COMPOUNDS
CARBOXYLIC ACIDS
CARDIOVASCULAR SYSTEM
CHROMATOGRAPHY
DOGS
HEART
HYDROGEN COMPOUNDS
ISOTOPE APPLICATIONS
ISOTOPE DILUTION
LABELLED COMPOUNDS
LEUCINE
LIQUID COLUMN CHROMATOGRAPHY
MAMMALS
METABOLISM
MUSCLES
MYOCARDIUM
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANS
PHENYLALANINE
PROTEINS
SEPARATION PROCESSES
TRACER TECHNIQUES
TRITIUM COMPOUNDS
VERTEBRATES