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Citric Acid Cycle Metabolites Predict the Severity of Myocardial Stunning and Mortality in Newborn Pigs.
- Source :
-
Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies [Pediatr Crit Care Med] 2016 Dec; Vol. 17 (12), pp. e567-e574. - Publication Year :
- 2016
-
Abstract
- Objectives: 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.<br />Design: 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.<br />Setting: University hospital animal laboratory.<br />Main Results: 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).<br />Conclusions: 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.
- Subjects :
- Animals
Cardiotonic Agents therapeutic use
Chromatography, Liquid
Dobutamine therapeutic use
Drug Therapy, Combination
Epinephrine therapeutic use
Female
Heart Failure drug therapy
Heart Failure metabolism
Heart Failure mortality
Microdialysis
Milrinone therapeutic use
Myocardial Stunning drug therapy
Myocardial Stunning metabolism
Myocardial Stunning mortality
Random Allocation
Severity of Illness Index
Sodium Chloride therapeutic use
Spectrometry, Mass, Electrospray Ionization
Swine
Tandem Mass Spectrometry
Treatment Outcome
Biomarkers metabolism
Citric Acid Cycle
Heart Failure diagnosis
Myocardial Stunning diagnosis
Subjects
Details
- Language :
- English
- ISSN :
- 1529-7535
- Volume :
- 17
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies
- Publication Type :
- Academic Journal
- Accession number :
- 27741040
- Full Text :
- https://doi.org/10.1097/PCC.0000000000000982