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

Michael E Jessen, Thomas E. Kovarik, F. Mark Jeffrey, Dean Sherry, Charles J. Storey, Robert Y. Chao, W Steves Ring, Craig R Malloy

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

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. 13C 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 [1,2-13C]acetate, [3-13C]lactate, 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.

Original languageEnglish (US)
Pages (from-to)831-839
Number of pages9
JournalJournal of Clinical Investigation
Volume92
Issue number2
StatePublished - Aug 1993

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Left Ventricular Function
Reperfusion
Ischemia
Aspartic Acid
Glutamic Acid
Amino Acids
Citric Acid Cycle
Lactic Acid
Acetates
Acetyl Coenzyme A
Metabolic Networks and Pathways
Myocardium
Carbon
Glucose

Keywords

  • Aspartate
  • Citric acid cycle metabolism
  • Glutamate
  • Ischemia
  • Myocardium
  • Nuclear magnetic resonance

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Effects of amino acids on substrate selection, anaplerosis, and left ventricular function in the ischemic reperfused rat heart. / Jessen, Michael E; Kovarik, Thomas E.; Jeffrey, F. Mark; Sherry, Dean; Storey, Charles J.; Chao, Robert Y.; Ring, W Steves; Malloy, Craig R.

In: Journal of Clinical Investigation, Vol. 92, No. 2, 08.1993, p. 831-839.

Research output: Contribution to journalArticle

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