• Janus Adler Hyldebrandt, Nicolaj Brejnholt Støttrup, Christian Alcaraz Frederiksen, Johan Heiberg, Rune Isak Dupont Birkler, Mogens Johannsen, Michael Rahbek Schmidt, and Hanne Berg Ravn.
• 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.
• Pediatr Crit Care Me. 2016 Dec 1; 17 (12): e567-e574.

ObjectivesMyocardial 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.DesignA 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.SettingUniversity hospital animal laboratory.Main ResultsIschemia-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).ConclusionsAccumulation 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.

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