Tricarboxylic acid cycle activity in postischemic rat hearts

Robert G. Weiss, Roberta Kalil-Filho, Ahvie Herskowitz, V. P. Chacko, Marc Litt, Michael D. Stern, Gary Gerstenblith

Research output: Contribution to journalArticlepeer-review

Abstract

Background. Although myocardial oxidative tricarboxylic acid (TCA) cycle activity and contractile function are closely linked in normal cardiac muscle, their relation during postischemic reperfusion, when contractility often is reduced, is not well defined. Methods and Results. To test the hypothesis that oxidative TCA cycle flux is reduced in reperfused myocardium with persistent contractile dysfunction, TCA cycle flux was measured by analyzing the time course of sequential myocardial glutamate labeling during 13C-labeled substrate infusion with 13C nuclear magnetic resonance spectroscopy in beating isolated rat hearts at 37°C. Total TCA cycle flux, indexed by both empirical and mathematical modeling analyses of the 13C data, was not reduced but rather increased in hearts reperfused after 17-20 minutes of ischemia (left ventricular pressure, 73±5% of preischemic values) compared with flux in developed pressure-matched controls (e.g., total flux, 2.5±0.4 versus 1.6±0.1 μmol·min-1·g wet wt-1, respectively; p<0.01). No TCA cycle activity was detectable by 13C nuclear magnetic resonance in hearts reperfused after 40-45 minutes of ischemia, which lacked contractile recovery and had ultrastructural evidence of irreversible injury. Conclusions. These results suggest that TCA cycle activity is not persistently decreased in dysfunctional reperfused myocardium after a brief ischemic episode and therefore cannot account for the reduced contractile function at that time.

Original languageEnglish (US)
Pages (from-to)270-282
Number of pages13
JournalCirculation
Volume87
Issue number1
DOIs
StatePublished - Jan 1993

Keywords

  • Contractility
  • Krebs cycle
  • Metabolism, intermediary
  • Myocardium, stunned
  • Nuclear magnetic resonance
  • Reperfusion
  • Spectroscopy
  • Tricarboxylic acid
  • Ultrastructure

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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