Altered Carnitine Homeostasis in Children With Increased Pulmonary Blood Flow Due to Ventricular Septal Defects.

Objectives: Congenital heart disease with increased pulmonary blood flow results in progressive pulmonary vascular endothelial dysfunction and associated increased perioperative morbidity. Using our ovine model of congenital heart disease with increased pulmonary blood flow, we have previously demonstrated progressive endothelial dysfunction associated with disruption in carnitine homeostasis, mitochondrial dysfunction, decreased nitric oxide signaling, and enhanced reactive oxygen species generation. However, potential alterations in these parameters in patients with congenital heart disease have not been investigated. The objective of this study was to test the hypothesis that children with increased pulmonary blood flow will have evidence of altered carnitine homeostasis, mitochondrial dysfunction, decreased nitric oxide levels, and increased reactive oxygen species generation. Design: A prospective single-center cohort study. Setting: A tertiary care cardiac ICU/PICU. Patients: Arterial blood samples from 18 patients with congenital heart disease associated with increased pulmonary blood flow (ventricular septal defect), 20 with congenital heart disease without increased pulmonary blood flow (tetralogy of Fallot), and 10 without heart disease (controls) were obtained. Interventions: Plasma levels of total carnitine, free carnitine, acylcarnitine, and lactate-to-pyruvate ratios, an indicator of mitochondrial function, were determined and compared. In addition, levels of superoxide and hydrogen peroxide were determined and compared in patients with ventricular septal defect and controls. Statistical analysis was performed using an unpaired t test and analysis of variance. Measurements and Main Results: Baseline acylcarnitine levels (25.7 +/- 13 vs 12.7 +/- 8.3; p

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