Analysis of control of glycolysis in ischemic hearts having heterogeneous zones of anoxia

Charles Jr Steenbergen, Gilbert Deleeuw, John R. Williamson

Research output: Contribution to journalArticle

Abstract

The effects of hypercapnia have been studied in rat hearts perfused with glucose and insulin. At pH 6.7 to 6.8, two different responses were observed. One was characterized by a rapid decrease in pressure development followed by a gradual recovery of contractile function. The tissue was uniformly aerobic, ATP levels were well maintained, the cytosolic and mitochondrial pyridine nucleotides were significantly more oxidized than during control conditions, and glycolytic flux was decreased due to inhibition of phosphofructokinase. In the second type of response, there was an uneven distribution of coronary perfusion with anoxic areas appearing in regions where flow was most restricted, and myocardial function remained severely impaired. Unperfused vessels and anoxic tissue were shown to exist throughout the myocardium under these conditions. Whole-tissue ATP levels were significantly decreased and NADH levels increased, reflecting impaired electron transport and oxidative phosphorylation. The problem of interpretation of total tissue metabolite contents in heterogeneously oxygenated tissue was resolved by calculation of the proportion of aerobic to anaerobic tissue in these hearts. In the anaerobic portions of ischemic hearts, glycolysis was inhibited at the level of glyceraldehyde 3-P dehydrogenase due to increased cytosolic NADH and decreased intracellular pH. Calculations of cytosolic and mitochondrial ATP/ADP ratios and phosphate potentials suggest (a) that the cytosolic free Mg2+ concentration was 0.6 to 0.7 mM in aerobic hearts, but was much lowerin anaerobic hearts, (b) that the rate of respiration did not depend solely on the cytosolic phosphate potential but was also influenced by the mitochondrial NAD redox state, and (c) that the estimated phosphorylation potential of aerobic hearts was 3.5 kcal/mol higher in the cytosol than in the mitochondria.

Original languageEnglish (US)
JournalJournal of Molecular and Cellular Cardiology
Volume10
Issue number7
DOIs
StatePublished - 1978
Externally publishedYes

Fingerprint

Glycolysis
NAD
Adenosine Triphosphate
Phosphates
Glyceraldehyde
Phosphofructokinases
Hypercapnia
Oxidative Phosphorylation
Recovery of Function
Electron Transport
Cytosol
Adenosine Diphosphate
Oxidation-Reduction
Hypoxia
Myocardium
Mitochondria
Oxidoreductases
Respiration
Nucleotides
Perfusion

Keywords

  • Anoxia
  • Cardiac ischemia
  • Glyceraldehyde-3-P-dehydrogenase
  • Glycolysis
  • NADH fluorescence photography
  • Perfused rat heart
  • Phosphofructokinase
  • Respiratory acidosis

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

Cite this

Analysis of control of glycolysis in ischemic hearts having heterogeneous zones of anoxia. / Steenbergen, Charles Jr; Deleeuw, Gilbert; Williamson, John R.

In: Journal of Molecular and Cellular Cardiology, Vol. 10, No. 7, 1978.

Research output: Contribution to journalArticle

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