Requirement of glycolytic substrate for metabolic recovery during moderate low flow ischemia

Saul Schaefer, Erik Prussel, Laurence J. Carr

Research output: Contribution to journalArticlepeer-review

36 Scopus citations

Abstract

Requirement of Glytolytic Substrate for Metabolic Recovery During Moderate Low Flow Ischemia. Journal of Molecular and Cellular Cardiology (1995) 27, 2167-2176. Low flow ischemia with stable hemodynamic function can result in partial metabolic recovery characterized by an increase in phosphocreative (PCr). Prior data suggest that glytolytic production of adenosine triphosphate (ATP) may be critical for this recovery and that the ATP produced by oxidative phosphorylation alone may be insufficient. This study tested the hypothesis that, during moderate low flow ischemia, (a) metabolic recovery is dependent on glycolytic production of ATP, and, therefore, (b) a mitochondrial substrate such as pyruvate alone is inadequate to allow metabolic recovery. High energy phosphates, pH, and lactate release were measured during 2 h of moderate low flow ischemia. Hearts were perfused with either a glycolytic plus mitochondrual substrate (glucose, insulin and pyruvate) or a mitochondrial substrate alone (pyruvate). Flow reductions required to reduced PCr by approximately 8% resulted in stable and equal reductiond of rate-pressure product in each group. PCr recovered fully during the ischemic period in control hearts with glycolytics substrate, associated with preservation of normal end-diastolic pressure, and increased lactate release during the first hour of ischemia. Reperfusion of these hearts restored hemodynamic function and increased PCr above baseline values. In contrast, the use of pyruvate alone as a substrate resulted in a progressive fall of PCr during ischemia, increased end-diastolic pressure, and no significant increase in lactate release. Reperfusion in these hearts restored hemodynamic function, but did not result in normalization of PCr. Both groups had significant reductions in ATP during ischemia. Recovery of PCr during ongoing moderate low flow ischemia is observed in the presence of mixed glycolytic and mitochondrial substrates (glucose, insulin and pyruvate) but is not observed with pyruvate as a sole mitochondrial substrate. These data support a critical role for glycolytic flux under these conditions, suggesting that ATP generated solely by oxidative phosphorylation is not sufficient to promote metabolic recovery or maintain diastolic function during moderate low flow ischemia.

Original languageEnglish (US)
Pages (from-to)2167-2176
Number of pages10
JournalJournal of Molecular and Cellular Cardiology
Volume27
Issue number10
StatePublished - Oct 1995

Keywords

  • High energy phosphates
  • Myocardial metabolism
  • NMR spectroscopy
  • Viable myocardium

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Molecular Biology

Fingerprint

Dive into the research topics of 'Requirement of glycolytic substrate for metabolic recovery during moderate low flow ischemia'. Together they form a unique fingerprint.

Cite this