Effect of hyperglycemia and fatty acid oxidation inhibition during aerobic conditions and demand-induced ischemia.

Abstract

Metabolic interventions improve performance during demand-induced ischemia by reducing myocardial lactate production and improving regional systolic function. We tested the hypotheses that 1) stimulation of glycolysis would increase lactate production and improve ventricular wall motion, and 2) the addition of fatty acid oxidation inhibition would reduce lactate production and further improve contractile function. Measurements were made in anesthetized open-chest swine hearts. Three groups, hyperglycemia (HG), HG + oxfenicine (HG + Oxf), and control (CTRL), were treated under aerobic conditions and during demand-induced ischemia. During demand-induced ischemia, HG resulted in greater lactate production and tissue lactate content but had no significant effect on glucose oxidation. HG + Oxf significantly lowered lactate production and increased glucose oxidation compared with both the CTRL and HG groups. Myocardial energy efficiency was greater in the HG and HG + Oxf groups under aerobic conditions but did not change during demand-induced ischemia. Thus enhanced glycolysis resulted in increased energy efficiency under aerobic conditions but significantly enhanced lactate production with no further improvement in function during demand-induced ischemia. Partial inhibition of free fatty acid oxidation in the presence of accelerated glycolysis increased energy efficiency under aerobic conditions and significantly reduced lactate production and enhanced glucose oxidation during demand-induced ischemia.

• Authors: Pedro N Chavez, William C Stanley, Tracy A McElfresh, Hazel Huang, Joseph P Sterk, Margaret P Chandler
• Journal: American journal of physiology. Heart and circulatory physiology (Am J Physiol Heart Circ Physiol) Vol. 284 Issue 5 Pg. H1521-7 (May 2003) ISSN: 0363-6135 [Print] United States
• PMID: 12521928 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Fatty Acids, Nonesterified
• Lactic Acid
• Glycogen

Topics

• Animals
• Coronary Circulation (physiology)
• Disease Models, Animal
• Fatty Acids, Nonesterified (metabolism)
• Glycogen (metabolism)
• Glycolysis (physiology)
• Hyperglycemia (metabolism)
• Lactic Acid (metabolism)
• Myocardial Ischemia (metabolism)
• Myocardium (metabolism)
• Oxidation-Reduction
• Physical Conditioning, Animal (physiology)
• Sus scrofa
• Ventricular Function, Left (physiology)