Studies of metabolism in the isolated, perfused rat heart using <sup>13</sup>C NMR

Bailey, Ian A.; Gadian, David G.; Matthews, Paul M.; Radda, G; Seeley, P.J.

doi:10.1016/0014-5793(81)80317-1

Cited by 90 publications

(46 citation statements)

References 18 publications

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“…Hyperpolarized [1-13 C]pyruvate was used to assess flux through PDH qualitatively by comparing the observed H 13 CO 3 Ϫ production in control rats with H 13 CO 3 Ϫ production in fasted and diabetic rats. The alterations in PDH flux as determined with hyperpolarized 13 C MR are in line with previous measurements of PDH activity in each of these conditions, made with conventional destructive methods (3,(23)(24)(25)(26). This work has provided preliminary evi-dence that hyperpolarized 13 C MR may be a useful technique for the noninvasive determination of metabolic fluxes in the heart.…”

supporting

confidence: 69%

“…To date, measurement of cardiac PDH activity has been performed with invasive biochemical assays, whereas substrate selection has been monitored via radiolabeling (10)(11)(12) or carbon-13 ( 13 C) magnetic resonance (MR) spectroscopy in the isolated perfused heart (13,14). These techniques are not feasible for monitoring PDH repeatedly in the same organism, however, or for clinical diagnosis.…”

mentioning

confidence: 99%

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In vivo assessment of pyruvate dehydrogenase flux in the heart using hyperpolarized carbon-13 magnetic resonance

Schroeder

Cochlin

Heather

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

239

352

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The advent of hyperpolarized 13 C magnetic resonance (MR) has provided new potential for the real-time visualization of in vivo metabolic processes. The aim of this work was to use hyperpolarized [1-13 C]pyruvate as a metabolic tracer to assess noninvasively the flux through the mitochondrial enzyme complex pyruvate dehydrogenase (PDH) in the rat heart, by measuring the production of bicarbonate (H 13 CO 3 ؊ ), a byproduct of the PDH-catalyzed

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supporting

confidence: 69%

mentioning

confidence: 99%

In vivo assessment of pyruvate dehydrogenase flux in the heart using hyperpolarized carbon-13 magnetic resonance

Schroeder

Cochlin

Heather

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

239

352

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“…Natural abundance laC spectroscopy at 15 MHz was used subsequently to identify taurine and betaine in adductor muscles of molluscs [9]. Recently, the oxidation of acetate in the Krebs cycle was followed by perfusing heart with [laC]acetate labeled in the methyl carbon [ 10].…”

Section: Introductionmentioning

confidence: 99%

Natural abundance ¹³C NMR spectra of intact muscle

1981

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“…While radiotracer experiments can noninvasively index tissue uptake of substrate in beating hearts, they cannot provide direct insight into the metabolic fate of that substrate (8,9). '3C NMR spectroscopy provides the ability to nondestructively characterize substrate metabolism in the intact heart and to correlate measured changes with 31P NMR indices of high-energy phosphate levels and pH (10)(11)(12)(13)(14)(15)(16)(17) Protocol. After stabilization, natural-abundance 13C and baseline 31p spectra were obtained.…”

mentioning

confidence: 99%

Comparative 13C and 31P NMR assessment of altered metabolism during graded reductions in coronary flow in intact rat hearts.

Weiss

Chacko

Glickson

et al. 1989

Proc. Natl. Acad. Sci. U.S.A.

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ABSTRACT13C NMR spectroscopy may offer a unique ability to characterize the metabolic response to graded reductions in coronary flow since it allows repeated, nondestructive identification of products of intermediary metabolism in the same heart. The sensitivity of 13C parameters of glucose metabolism was compared with changes in levels of phosphocreatine, ATP, and pH as determined by 31p NMR in the intact, beating rat heart model during graded reductions in coronary flow. Experiments were performed during 60 min of perfusion with [1-'3C]glucose (5 mM) at normal flow (15 ml/min) and at the reduced flow rates of 5 and 2 ml/min. During flow at 5 ml/min, isovolumic developed pressure fell to 51 ± 4% of control. Although phosphocreatine, ATP, and pH were not changed, [3-13C]lactate was increased (1.46 ± 0.12 ,umol/g of wet weight vs. 0.63 ± 0.08 during normal flow). In addition, the time to 50% maximum enrichment of [2-13C]glutamate was prolonged (17 ± 1 min vs. 9 ± 1 min during normal flow), indicating that glucose-supported flux through the tricarboxylic acid (TCA) cycle was decreased. The relative anaplerotic contribution to citrate synthase-supported TCA flux was increased from 6% to 35%. These 13C metabolic changes could not be reproduced by reduced [1-'3C]glucose delivery in the absence of ischemia, although similar reduced TCA flux indices were reproduced in additional hearts when workload was reduced by low calcium (0.7 mM) perfusion. Therefore, the information provided by 13C NMR spectroscopy can be a more sensitive indicator of flow-induced alterations in cardiac metabolism than that provided by the much more commonly used 31P NMR technique.The metabolic consequences of myocardial ischemia have been detected and quantitated by the use of noninvasive 31P NMR measures of high-energy phosphate levels and pH (1-4) and by wet chemical analyses of metabolites in digested tissue (5, 6). Wet chemical techniques are limited by their destructive nature, which eliminates intracellular metabolite compartmentation (7), do not permit repeated measures on the same heart during experimental interventions, and do not allow the simultaneous study of altered physiologic factors such as workload. While radiotracer experiments can noninvasively index tissue uptake of substrate in beating hearts, they cannot provide direct insight into the metabolic fate of that substrate (8, 9).'3C NMR spectroscopy provides the ability to nondestructively characterize substrate metabolism in the intact heart and to correlate measured changes with 31P NMR indices of high-energy phosphate levels and pH (10-17 The purpose of the present study was to characterize glucose metabolism by using 13C NMR spectroscopy during moderate reductions in coronary flow and to compare the relative sensitivity of these 13C NMR indices with highenergy phosphate levels and pH obtained by 31P NMR techniques. METHODSHeart Preparation. Hearts from non-fasting, male, retired breeder Wistar rats (body weight, 450-650 g), anesthetized with sodium pentobarbital, were rapid...

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Studies of metabolism in the isolated, perfused rat heart using ¹³C NMR

Cited by 90 publications

References 18 publications

In vivo assessment of pyruvate dehydrogenase flux in the heart using hyperpolarized carbon-13 magnetic resonance

In vivo assessment of pyruvate dehydrogenase flux in the heart using hyperpolarized carbon-13 magnetic resonance

Natural abundance ¹³C NMR spectra of intact muscle

Comparative 13C and 31P NMR assessment of altered metabolism during graded reductions in coronary flow in intact rat hearts.

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Studies of metabolism in the isolated, perfused rat heart using 13C NMR

Cited by 90 publications

References 18 publications

In vivo assessment of pyruvate dehydrogenase flux in the heart using hyperpolarized carbon-13 magnetic resonance

In vivo assessment of pyruvate dehydrogenase flux in the heart using hyperpolarized carbon-13 magnetic resonance

Natural abundance 13C NMR spectra of intact muscle

Comparative 13C and 31P NMR assessment of altered metabolism during graded reductions in coronary flow in intact rat hearts.

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Product

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Studies of metabolism in the isolated, perfused rat heart using ¹³C NMR

Natural abundance ¹³C NMR spectra of intact muscle