title: Brief increase in carbohydrate oxidation after reperfusion reverses myocardial stunning in conscious pigs.
abstract: BACKGROUND
  Previous studies have examined only acute effects of enhanced glucose oxidation on postischemic myocardium. The goal of the present study was to examine prolonged functional recovery subsequent to postischemic, intracoronary pyruvate dehydrogenase kinase inhibition with dichloroacetate (DCA) of stunned myocardium in conscious pigs.
  
  
  RESULTS
  Myocardial stunning was induced in conscious pigs by coronary stenosis, ie, 40% reduction of coronary blood flow for 90 minutes, followed by full reperfusion. After the initial peak, but during early reactive hyperemia (5 minutes of reperfusion), 1 hour of intracoronary infusion at 20% of measured coronary blood flow was begun using 20 mmol/L [2-(13)C]glucose without (n=4) or with (n=5) 20 mmol/L DCA. Coronary stenosis resulted in similar reduction in wall thickening in both untreated (-53+/-3% from 3.27+/-0.22 mm, n=9) and DCA (-51+/-3% from 3.08+/-0.15 mm, n=5) groups. During reperfusion, DCA increased glucose oxidation 10-fold. In the absence of DCA, myocardial stunning was observed; ie, wall thickening was reduced by 48+/-3% at 1 hour of reperfusion and did not fully recover for 48 hours. In contrast, in DCA pigs, myocardial stunning was ameliorated (P<0.05).
  
  
  CONCLUSIONS
  Transient metabolic intervention within a clinically relevant time after ischemia eliminates myocardial stunning in conscious pigs during augmented carbohydrate oxidation and provides sustained benefits in contractile recovery.
authors.affiliation: Program in Integrative Cardiac Metabolism, Department of Physiology and Biophysics, University of Illinois at Chicago College of Medicine, Chicago, IL 60612, USA.
authors.forename: Raymond K
authors.initials: RK
authors.lastname: Kudej
authors.forename: Lawrence T
authors.initials: LT
authors.lastname: White
authors.forename: Amelia B
authors.initials: AB
authors.lastname: Kudej
authors.forename: Stephen F
authors.initials: SF
authors.lastname: Vatner
authors.forename: E Douglas
authors.initials: ED
authors.lastname: Lewandowski
mesh_terms: D000818:Animals; D001783:Blood Flow Velocity / Q000187:drug effects; D050260:Carbohydrate Metabolism; D003243:Consciousness; D003326:Coronary Circulation / Q000187:drug effects; D023921:Coronary Stenosis / Q000150:complications; D003999:Dichloroacetic Acid / Q000494:pharmacology; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects; D007269:Injections, Intra-Arterial; D009200:Myocardial Contraction / Q000187:drug effects; D015425:Myocardial Reperfusion; D017682:Myocardial Stunning / Q000209:etiology / Q000503:physiopathology* / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D010084:Oxidation-Reduction / Q000187:drug effects; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D020127:Recovery of Function / Q000187:drug effects; D013552:Swine; D013995:Time
chemical_list: D004791:Enzyme Inhibitors; D047428:Protein Kinase Inhibitors; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D003999:Dichloroacetic Acid; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D005947:Glucose