title: ATP synthesis during low-flow ischemia: influence of increased glycolytic substrate.
abstract: BACKGROUND
  Our goals were to (1) simulate the degree of low-flow ischemia and mixed anaerobic and aerobic metabolism of an acutely infarcting region; (2) define changes in anaerobic glycolysis, oxidative phosphorylation, and the creatine kinase (CK) reaction velocity; and (3) determine whether and how increased glycolytic substrate alters the energetic profile, function, and recovery of the ischemic myocardium in the isolated blood-perfused rat heart.
  
  
  RESULTS
  Hearts had 60 minutes of low-flow ischemia (10% of baseline coronary flow) and 30 minutes of reperfusion with either control or high glucose and insulin (G+I) as substrate. In controls, during ischemia, rate-pressure product and oxygen consumption decreased by 84%. CK velocity decreased by 64%; ATP and phosphocreatine (PCr) concentrations decreased by 51% and 63%, respectively; inorganic phosphate (P(i)) concentration increased by 300%; and free [ADP] did not increase. During ischemia, relative to controls, the G+I group had similar CK velocity, oxygen consumption, and tissue acidosis but increased glycolysis, higher [ATP] and [PCr], and lower [P(i)] and therefore had a greater free energy yield from ATP hydrolysis. Ischemic systolic and diastolic function and postischemic recovery were better.
  
  
  CONCLUSIONS
  During low-flow ischemia simulating an acute myocardial infarction region, oxidative phosphorylation accounted for 90% of ATP synthesis. The CK velocity fell by 66%, and CK did not completely use available PCr to slow ATP depletion. G+I, by increasing glycolysis, slowed ATP depletion, maintained lower [P(i)], and maintained a higher free energy from ATP hydrolysis. This improved energetic profile resulted in better systolic and diastolic function during ischemia and reperfusion. These results support the clinical use of G+I in acute MI.
authors.affiliation: Cardiac Muscle Research Laboratory, Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, MA, USA.
authors.forename: A C
authors.initials: AC
authors.lastname: Cave
authors.forename: J S
authors.initials: JS
authors.lastname: Ingwall
authors.forename: J
authors.initials: J
authors.lastname: Friedrich
authors.forename: R
authors.initials: R
authors.lastname: Liao
authors.forename: K W
authors.initials: KW
authors.lastname: Saupe
authors.forename: C S
authors.initials: CS
authors.lastname: Apstein
authors.forename: F R
authors.initials: FR
authors.lastname: Eberli
mesh_terms: D000255:Adenosine Triphosphate / Q000096:biosynthesis*; D000818:Animals; D003402:Creatine Kinase / Q000378:metabolism; D004195:Disease Models, Animal; D005947:Glucose / Q000378:metabolism / Q000502:physiology; D006439:Hemodynamics; D007328:Insulin / Q000502:physiology; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009203:Myocardial Infarction / Q000378:metabolism; D017202:Myocardial Ischemia / Q000378:metabolism* / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism*; D010085:Oxidative Phosphorylation; D010101:Oxygen Consumption; D010725:Phosphocreatine / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
chemical_list: D007328:Insulin; D010725:Phosphocreatine; D000255:Adenosine Triphosphate; D003402:Creatine Kinase; D005947:Glucose