title: Citric Acid Cycle Metabolites Predict the Severity of Myocardial Stunning and Mortality in Newborn Pigs.
abstract: Myocardial infarction and chronic heart failure induce specific metabolic changes in the neonatal myocardium that are closely correlated to outcome. The aim of this study was to examine the metabolic responses to noninfarct heart failure and inotropic treatments in the newborn heart, which so far are undetermined.
  
  
  
  A total of 28 newborn pigs were instrumented with a microdialysis catheter in the right ventricle, and intercellular citric acid cycle intermediates and adenosine metabolite concentrations were determined at 20-minute intervals. Stunning was induced by 10 cycles of 3 minutes of ischemia, which was performed by occluding the right coronary artery, followed by 3 minutes of reperfusion. Animals were randomized for treatment with epinephrine + milrinone, dopamine + milrinone, dobutamine, or saline.
  
  
  
  University hospital animal laboratory.
  
  
  
  Ischemia-reperfusion induced right ventricular stunning and increased the concentrations of pyruvate lactate, succinate, malate, hypoxanthine, and xanthine (all, p < 0.01). During inotrope infusion, no differences in metabolite concentrations were detected between the treatment groups. In nonsurviving animals (n = 8), concentrations of succinate (p < 0.0001), malate (p = 0.009), and hypoxanthine (p = 0.04) increased compared with survivors, while contractility was significantly reduced (p = 0.03).
  
  
  
  Accumulation of citric acid cycle intermediates and adenosine metabolites reflects the presence of myocardial stunning and predicts mortality in acute noninfarct right ventricular heart failure in newborn pigs. This phenomenon occurs independently of the type of inotrope, suggesting that citric acid cycle intermediates represent potential markers of acute noninfarct heart failure.
authors.affiliation: 1Department of Anesthesiology and Intensive Care, Aarhus University Hospital, Skejby, Denmark.2Department of Cardiology, Akershus University Hospital, Lørenskog, Norway.3Department of Cardiology, Aarhus University Hospital, Skejby, Denmark.4Department of Cardiology, Randers Regional Hospital, Randers, Denmark.5Department Thoracic and Vascular Surgery, Aarhus University Hospital, Skejby, Denmark.6Section for Forensic Chemistry, Department of Forensic Medicine, Aarhus University, Aarhus, Denmark.7The Heart Center, Department of Cardiothoracic Anesthesiology, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Janus Adler
authors.initials: JA
authors.lastname: Hyldebrandt
authors.forename: Nicolaj Brejnholt
authors.initials: NB
authors.lastname: Støttrup
authors.forename: Christian Alcaraz
authors.initials: CA
authors.lastname: Frederiksen
authors.forename: Johan
authors.initials: J
authors.lastname: Heiberg
authors.forename: Rune Isak
authors.initials: RI
authors.lastname: Dupont Birkler
authors.forename: Mogens
authors.initials: M
authors.lastname: Johannsen
authors.forename: Michael Rahbek
authors.initials: MR
authors.lastname: Schmidt
authors.forename: Hanne Berg
authors.initials: HB
authors.lastname: Ravn
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism*; D002316:Cardiotonic Agents / Q000627:therapeutic use; D002853:Chromatography, Liquid; D002952:Citric Acid Cycle; D004280:Dobutamine / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D004837:Epinephrine / Q000627:therapeutic use; D005260:Female; D006333:Heart Failure / Q000175:diagnosis* / Q000188:drug therapy / Q000378:metabolism / Q000401:mortality; D017551:Microdialysis; D020105:Milrinone / Q000627:therapeutic use; D017682:Myocardial Stunning / Q000175:diagnosis* / Q000188:drug therapy / Q000378:metabolism / Q000401:mortality; D011897:Random Allocation; D012720:Severity of Illness Index; D012965:Sodium Chloride / Q000627:therapeutic use; D021241:Spectrometry, Mass, Electrospray Ionization; D013552:Swine; D053719:Tandem Mass Spectrometry; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D002316:Cardiotonic Agents; D004280:Dobutamine; D012965:Sodium Chloride; D020105:Milrinone; D004837:Epinephrine