title: Second window of preconditioning normalizes palmitate use for oxidation and improves function during low-flow ischaemia.
abstract: OBJECTIVE
  Although a major mechanism for cardioprotection is altered metabolism, little is known regarding metabolic changes in ischaemic preconditioning and subsequent ischaemia. Our objective was to examine the effects of the second window of preconditioning (SWOP), the delayed phase of preconditioning against infarction and stunning, on long-chain free fatty acid (LCFA) oxidation during ischaemia in chronically instrumented, conscious pigs.
  
  
  RESULTS
  We studied three groups: (i) normal baseline perfusion (n = 5); (ii) coronary artery stenosis (CAS; n = 5); (iii) CAS 24 h following 2 × 10 min coronary occlusions and 10 min reperfusion (n = 7). Ischaemia was induced by a left anterior descending (LAD) stenosis (40% flow reduction) for 90 min, dropping systolic wall thickening by 72%. LCFA oxidation was assessed following LAD infusion of (13)C palmitate, i.e. during control or stenosis, by in vitro nuclear magnetic resonance of the sampled myocardium. Stenosis reduced subendocardial blood flow subendocardially, but not subepicardial, yet induced transmural reductions in LCFA oxidation and increased non-oxidative glycolysis. During stenosis, preconditioned hearts showed normalized contributions of LCFA to oxidative ATP synthesis, despite increased lactate accumulation. SWOP induced a shift towards LCFA oxidation during stenosis, despite increased malonyl-CoA, and marked protection of contractile function with a significant improvement in systolic wall thickening.
  
  
  CONCLUSIONS
  Thus, the second window of preconditioning normalized oxidative metabolism of LCFA during subsequent ischaemia despite elevated non-oxidative glycolysis and malonyl-CoA and was linked to protection of regional contractile function resulting in improved mechanical performance. Interestingly, the metabolic responses occurred transmurally while ischaemia was restricted solely to the subendocardium.
authors.affiliation: Department of Cell Biology and Molecular Medicine,  University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, NJ,  USA.
authors.forename: Raymond K
authors.initials: RK
authors.lastname: Kudej
authors.forename: Mathew
authors.initials: M
authors.lastname: Fasano
authors.forename: Xin
authors.initials: X
authors.lastname: Zhao
authors.forename: Gary D
authors.initials: GD
authors.lastname: Lopaschuk
authors.forename: Susan K
authors.initials: SK
authors.lastname: Fischer
authors.forename: Dorothy E
authors.initials: DE
authors.lastname: Vatner
authors.forename: Stephen F
authors.initials: SF
authors.lastname: Vatner
authors.forename: E Douglas
authors.initials: ED
authors.lastname: Lewandowski
mesh_terms: D000105:Acetyl Coenzyme A / Q000378:metabolism; D000818:Animals; D003326:Coronary Circulation; D023921:Coronary Stenosis / Q000150:complications / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D004195:Disease Models, Animal; D004734:Energy Metabolism; D006019:Glycolysis; D006439:Hemodynamics; D019157:Ischemic Preconditioning, Myocardial; D008316:Malonyl Coenzyme A / Q000378:metabolism; D009200:Myocardial Contraction; D009203:Myocardial Infarction / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D015428:Myocardial Reperfusion Injury / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D017682:Myocardial Stunning / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism*; D010084:Oxidation-Reduction; D019308:Palmitic Acid / Q000008:administration & dosage / Q000378:metabolism*; D020127:Recovery of Function; D034421:Sus scrofa; D013997:Time Factors; D016277:Ventricular Function, Left
chemical_list: D019308:Palmitic Acid; D008316:Malonyl Coenzyme A; D000105:Acetyl Coenzyme A