Comparative Effects of Aspartate and Glutamate during Myocardial Ischemia

Bush, Larry R.; Warren, Susan; Mesh, Charles L.; Lucchesi, Benedict R.

doi:10.1159/000137565

Cited by 11 publications

(6 citation statements)

References 14 publications

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“…This model of prolonged global normothermic ischemia and reperfusion was chosen to allow comparison to numerous previous investigations (14,16,17,20,31,46). '3C-NMR was used to test previous hypotheses regarding the effects of amino acids on substrate selection, anaplerosis, and functional recovery after ischemia.…”

Section: Discussionmentioning

confidence: 99%

“…aspartate and glutamate to cardioplegic solutions during ( 17) or after (47) ischemia also has been associated with superior recovery of function during the reperfusion period.…”

Section: Discussionmentioning

confidence: 99%

“…However, succinyl-CoA generation from a-ketoglutarate requires NAD+, which is depleted during ischemia. Some authors have suggested that oxaloacetate derived from aspartate may oxidize NADH via reversal of malate dehydrogenase and therefore support a greater role for aspartate than glutamate in ischemic protection ( 17). Furthermore, others have demonstrated a direct inhibitory effect of glutamate on pyruvate carboxylase (50) in other tissues, which is thought to be a major anaplerotic mechanism in the heart ( 51 ).…”

Section: Discussionmentioning

confidence: 99%

“…Of perhaps greater significance is the potential for improving recovery after ischemia by deliberately modifying carbon flow into the citric acid cycle. For example, a protective effect of aspartate and glutamate in models of myocardial ischemia is widely recognized (13)(14)(15)(16)(17) and application in clinical trials is underway ( 1 8, 19). Under normal conditions, amino acids contribute little to acetyl-CoA, but, in post-ischemic myocardium, aspartate and glutamate may indirectly alter substrate selection by stimulating both pyruvate transamination and glycolysis (20).…”

Section: Introductionmentioning

confidence: 99%

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Effects of amino acids on substrate selection, anaplerosis, and left ventricular function in the ischemic reperfused rat heart.

Jessen¹,

Kovarik²,

Jeffrey³

et al. 1993

J. Clin. Invest.

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The effect of aspartate and glutamate on myocardial function during reperfusion is controversial. A beneficial effect has been attributed to altered delivery of carbon into the citric acid cycle via substrate oxidation or by stimulation of anaplerosis, but these hypotheses have not been directly tested. "C isotopomer analysis is well suited to the study of myocardial metabolism, particularly where isotopic and metabolic steady state cannot be established. This technique was used to evaluate the effects of aspartate and glutamate (amino acids, AA) on anaplerosis and substrate selection in the isolated rat heart after 25 min of ischemia followed by 30 or 45 min of reperfusion. Five groups of hearts (n = 8) provided with a mixture of 11,2-'3Clacetate, 13-13Cllactate, and unlabeled glucose were studied: control, control plus AA, ischemia followed by 30 min of reperfusion, ischemia plus AA followed by 30 min of reperfusion, and ischemia followed by 45 min of reperfusion. The contribution of lactate to acetyl-CoA was decreased in postischemic myocardium (with a significant increase in acetate), and anaplerosis was stimulated. Metabolism of 13C-labeled aspartate or glutamate could not be detected, however, and there was no effect of AA on functional recovery, substrate selection, or anaplerosis. Thus, in contrast to earlier reports, aspartate and glutamate have no effect on either functional recovery from ischemia or on metabolic pathways feeding the citric acid cycle. (J. Clin. Invest. 1993. 92:831-839.)

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Section: Discussionmentioning

confidence: 99%

“…aspartate and glutamate to cardioplegic solutions during ( 17) or after (47) ischemia also has been associated with superior recovery of function during the reperfusion period.…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Effects of amino acids on substrate selection, anaplerosis, and left ventricular function in the ischemic reperfused rat heart.

Jessen¹,

Kovarik²,

Jeffrey³

et al. 1993

J. Clin. Invest.

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“…Glutamate at higher concentrations (20 mM), during underperfusion of isolated rat hearts, greatly reduces the resulting contractile disfunction [32]. Addition of aspartate and glutamate to cardioplegic solution, during [33] or after [34] ischemia, has also been associated with superior recovery of function during the reperfusion period. These functional benefits have been attributed to several mechanisms.…”

Section: Ia Glutamate/glutaminementioning

confidence: 99%

The Role of Amino Acids in the Modulation of Cardiac Metabolism During Ischemia and Heart Failure

Marazzi

Rosanio²,

Caminiti

et al. 2008

CPD

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During ischemia and heart failure, myocardial cells suffer for chronic energy starvation resulting in metabolic and contractile dysfunction. In normal conditions fatty acids, glucose, and lactate are the principal oxidative fuels in myocardium, while amino acids serve a minor role as an oxidative fuel. However, in pathological conditions, myocardial uptake of several amino acids increases significantly as a consequence of a metabolic remodelling. Amino acids are involved in a variety of key biochemical and physiological activities, that counteract the deleterious cellular effects of reduced oxygen availability. Several amino acids are a direct source of substrate for energy production, and they modulate the activity of some enzymes involved in the glucose metabolism. They increase contractile performance both in isolated animal and human myocardium. Furthermore, amino acids improve the oxidative stress counteracting the action of radical oxygen species, being either precursors of glutathione synthesis, or of substrate of nitric oxide biosynthesis; they act on endothelial function and increase protein synthetic efficiency of myocardial cells by regulating gene expression and modulating hormonal activity. An amount of studies have demonstrated that amino acids administration, on patients with ischemic heart disease and heart failure, can improve several clinical endpoints. Here, we present an overview of the principal effects of the most experienced amino acids and of amino acid derivatives on ischemia and heart failure.

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Improved myocardial preservation during cold storage using substrate enhancement

Haan¹,

Lazar²,

Rivers³

et al. 1990

The Annals of Thoracic Surgery

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Comparative Effects of Aspartate and Glutamate during Myocardial Ischemia

Cited by 11 publications

References 14 publications

Effects of amino acids on substrate selection, anaplerosis, and left ventricular function in the ischemic reperfused rat heart.

Effects of amino acids on substrate selection, anaplerosis, and left ventricular function in the ischemic reperfused rat heart.

The Role of Amino Acids in the Modulation of Cardiac Metabolism During Ischemia and Heart Failure

Improved myocardial preservation during cold storage using substrate enhancement

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