Pyruvate‐enhanced phosphorylation potential and inotropism in normoxic and postischemic isolated working heart

Bünger, Rolf; Mallet, Robert T.; Hartman, David S.

doi:10.1111/j.1432-1033.1989.tb14637.x

Cited by 216 publications

(167 citation statements)

References 58 publications

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“…It has been found in isolated mitochondria [218], in single cells [101], and in perfused whole-hearts [219]. The positive inotropic actions of pyruvate have also been noticed many times in vivo [219][220][221] and, more recently, in isolated myocytes [222]. In Table 3b, we document the increased work output per beat achieved when pyruvate replaces glucose or when it is present together with glucose.…”

Section: Modifiers Of Basal Metabolismmentioning

confidence: 60%

“…The pyruvate effect was shown in subsequent myothermic papers [68,99] and has been documented with various methodologies. It has been found in isolated mitochondria [218], in single cells [101], and in perfused whole-hearts [219]. The positive inotropic actions of pyruvate have also been noticed many times in vivo [219][220][221] and, more recently, in isolated myocytes [222].…”

Section: Modifiers Of Basal Metabolismmentioning

confidence: 99%

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Cardiac Basal Metabolism.

Gibbs

Loiselle²

2001

JJP

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The cardiac basal metabolism is the rate of energy expenditure of the quiescent myocardium. It is also called the resting metabolism or the arrested heart metabolism. It has been measured in numerous ways, and in vivo there is good evidence that it accounts for about 1/5 to 1/3 of the total energy flux. The difficulty arises, however, when the heart is stopped because the magnitude of the basal metabolism depends, as blood viscosity, on how and under what physiological condition it is measured. It is possible for the in vivo basal value to fall to less than 1/5 of its original value without cellular damage or to increase to values 5 times greater than its probable in vivo magnitude (i.e., to rise to values in excess of the energy flux of the normally beating heart) by altering the composition of the perfusion medium. We have written on this subject several times [1][2][3], but believe that developments in knowledge now make it possible for us to speculate in a more informed manner. Since several million openheart operations are performed on arrested hearts worldwide each year, it would seem imperative that we understand the cellular mechanisms that can change the magnitude of basal metabolism.A. V. Hill [4] has pointed out that in examining physiological activities, it is necessary to assume a baseline from which some quantity or rate can be measured. If the energy flux produced by the beating heart were very large compared with the energy flux of the arrested heart, baseline ambiguity would be relatively unimportant. But this is not so in regard to the heart; its basal metabolism is high. Within a species, the basal metabolism of cardiac tissue is several-fold higher than the resting metabolism of skeletal muscle and is an order of magnitude greater than the resting metabolism of amphibian skeletal muscle.Species differences are clearly evident in the magnitude of cardiac basal metabolism, and we believe that the major reason for these differences relates to the leakiness of cell membranes, such as those of the sarcolemma and sarcoplasmic reticulum and those of Japanese Journal of Physiology, 51, 399-426, 2001 Key words: whole hearts, isolated preparations, biochemical contributors, modifiers, species difference, temperature, substrate, hypoxia. Abstract:We endeavor to show that the metabolism of the nonbeating heart can vary over an extreme range: from values approximating those measured in the beating heart to values of only a small fraction of normal-perhaps mimicking the situation of nonflow arrest during cardiac bypass surgery. We discuss some of the technical issues that make it difficult to establish the magnitude of basal metabolism in vivo. We consider some of the likely contributors to its magnitude and point out that the biochemical reasons for a sizable fraction of the heart's basal ATP usage remain unresolved. We consider many of the physiological factors that can alter the basal metabolic rate, stressing the importance of substrate supply. We point out that the protective effect of hypothermia ...

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Section: Modifiers Of Basal Metabolismmentioning

confidence: 60%

Section: Modifiers Of Basal Metabolismmentioning

confidence: 99%

Cardiac Basal Metabolism.

Gibbs

Loiselle²

2001

JJP

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“…134 The decrease of malonylCoA results from the inhibition of ACC by a specific AMPdependent protein kinase activated by the AMP accumulation during ischemia. 134,135 The beneficial effect of pyruvate at reperfusion 136 and the fact that the utilization of fatty acids instead of glucose strongly impairs the efficiency of the reperfused heart 129,137 suggest that the anaplerotic pathway is also stimulated at reperfusion. Finally, glucose at reperfusion is also required to rebuild glycogen.…”

Section: Glucose Metabolism At Reperfusionmentioning

confidence: 99%

Glucose for the Heart

Depré¹,

Vanoverschelde²,

Taegtmeyer³

1999

Circulation

380

260

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“…Aside from oxaloacetate (OAA), pyruvate also supplies acetyl-CoA to the CAC. Both pyruvate carboxylation and decarboxylation were linked to some beneficial effects on heart function (16,(23)(24)(25)(26)(27), although the partitioning of pyruvate through these two reactions remains to be clarified. Using 14 C-and 13 C-labeled substrates, several authors documented the reciprocal regulation of pyruvate decarboxylation and fatty acid oxidation (see for example Refs.…”

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confidence: 99%

A 13C Mass Isotopomer Study of Anaplerotic Pyruvate Carboxylation in Perfused Rat Hearts

Comte

Vincent

Bouchard

et al. 1997

Journal of Biological Chemistry

113

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Anaplerotic pyruvate carboxylation was examined in hearts perfused with physiological concentrations of glucose, [U-13 C 3 ]lactate, and [U-13 C 3 ]pyruvate. Also, a fatty acid, [1-13 C]octanoate, or ketone bodies were added at concentrations providing acetyl-CoA at a rate resulting in either low or substantial pyruvate decarboxylation. Relative contributions of pyruvate and fatty acids to citrate synthesis were determined from the 13 C labeling pattern of effluent citrate by gas chromatography-mass spectrometry (see companion article, Comte, B., Vincent, G., Bouchard, B., and Des Rosiers, C. (1997) J. Biol. Chem. 272, 26117-26124). Precision on flux measurements of anaplerotic pyruvate carboxylation depended on the mix of substrates supplied to the heart. Anaplerotic fluxes were precisely determined under conditions where acetyl-CoA was predominantly supplied by ␤-oxidation, as it occurred with 0.2 or 1 mM octanoate. Then, anaplerotic pyruvate carboxylation provided 3-8% of the OAA moiety of citrate and was modulated by concentrations of lactate and pyruvate in the physiological range. Also, the contribution of pyruvate to citrate formation through carboxylation was equal to or greater than through decarboxylation. Furthermore, 13 C labeling data on tissue citric acid cycle intermediates and pyruvate suggest that (i) anaplerosis occurs also at succinate and (ii) cataplerotic malate decarboxylation is low. Rather, the presence of citrate in the effluent perfusate of hearts perfused with physiological concentrations of glucose, lactate, and pyruvate and concentrations of octanoate leading to maximal oxidative rates suggests a cataplerotic citrate efflux from mitochondria to cytosol. Taken altogether, our data raise the possibility of a link between pyruvate carboxylation and mitochondrial citrate efflux. In view of the proposed feedback regulation of glycolysis by cytosolic citrate, such a link would support a role of anaplerosis and cataplerosis in metabolic signal transmission between mitochondria and cytosol in the normoxic heart.

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Pyruvate‐enhanced phosphorylation potential and inotropism in normoxic and postischemic isolated working heart

Cited by 216 publications

References 58 publications

Cardiac Basal Metabolism.

Cardiac Basal Metabolism.

Glucose for the Heart

A 13C Mass Isotopomer Study of Anaplerotic Pyruvate Carboxylation in Perfused Rat Hearts

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