Glucose flux rate regulates onset of ischemic contracture in globally underperfused rat hearts.

Abstract

This study analyzes the importance of the source and rate of ATP production (glucose flux, glycogenolysis, and oxidative phosphorylation) in the prevention of ischemic contracture in isolated rat hearts. Ischemic contracture was initiated at about 10 minutes by buffer perfusion with nonglycolytic substrates whereas the addition of 11 mM glucose prevented contracture for 2 hours. Tissue values of ATP, phosphocreatine, and lactate could be dissociated from onset of ischemic contracture. In hearts perfused with acetate or free fatty acid, with 11 mM glucose, glycolytic ATP production was 2.3-2.8 mumol/g fresh wt/min; as initial rates of glycogenolysis fell, glycolysis was maintained by a steady increase of glucose flux to values in excess of 2 mumol ATP/g fresh wt/min. Decreasing the glucose flux by lowering the perfusate glucose or by the addition of 2-deoxyglucose precipitated ischemic contracture. When oxidative phosphorylation was further reduced by hypoxia, glucose still prevented ischemic contracture; however, when oxidative phosphorylation dropped to near zero (near-anoxic) rates, glycolysis was inhibited, and glucose could only delay ischemic contracture to about 45 minutes. Combined ATP production rates could be dissociated from contracture. The metabolic parameter that correlated best with prevention or delay of ischemic contracture was the rate of glycolytic flux from glucose, which in this model of global low-flow ischemia had to accelerate to provide a rate of ATP production from glucose in excess of 2 mumol/g fresh wt/min within 30 minutes of the start of ischemia to prevent ischemic contracture.

• Authors: P Owen, S Dennis, L H Opie
• Journal: Circulation research (Circ Res) Vol. 66 Issue 2 Pg. 344-54 (Feb 1990) ISSN: 0009-7330 [Print] United States
• PMID: 2297807 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Acetates
• Fatty Acids, Nonesterified
• Lactates
• Phosphocreatine
• Lactic Acid
• Adenosine Triphosphate
• Glycogen
• Glucose

Topics

• Acetates (pharmacology)
• Adenosine Triphosphate (metabolism)
• Animals
• Coronary Circulation
• Coronary Disease (metabolism, physiopathology)
• Fatty Acids, Nonesterified (pharmacology)
• Glucose (metabolism, pharmacology)
• Glycogen (metabolism)
• Heart (physiopathology)
• Lactates (metabolism)
• Lactic Acid
• Male
• Myocardial Contraction
• Phosphocreatine (metabolism)
• Rats
• Rats, Inbred Strains
• Time Factors