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Despite improvements in surgical techniques, ischemia-reperfusion injury (IR) with reduced ventricular functional recovery remains a major predictor of morbidity and mortality among newborns with congenital heart disease (CHD). Modulation of energy substrate metabolism positively affects IR in adult patients undergoing cardiac surgery. However, these findings cannot be extrapolated to newborns with CHD who may undergo obligatory maturational changes. We sought to determine age-related changes in major fatty acid (FA) and carbohydrate metabolism enzymes and their regulation at transcriptional level in human newborns with CHD undergoing corrective surgery. We also determined the difference in maturational changes in patients displaying hypertrophy and its correlation with functional recovery capacity.
Right ventricular specimens were collected from 59 newborns (age 0-200 days) undergoing surgery. Based on a z-score for right ventricular free wall thickness, patients were stratified as non-hypertrophied (34) or hypertrophied (25). Western blot analysis for major FA and glucose metabolism enzymes, and transcriptional regulatory proteins was performed. Clinical outcomes including post-surgical right and left ventricular functional recovery were also assessed.
Since shortly after birth, neonates displayed an age-related increase in of FA oxidation, and a decrease in carbohydrate oxidative capacity. Hypertrophied hearts displayed an overall reduced expression of key proteins involved in the transcriptional regulation of cardiac energy metabolism at the mitochondrial level, in this way suggesting a vulnerable energetic state. In support with this hypothesis, following surgery, patients displaying hypertrophy presented with a worse ventricular functional recovery. The effects of hypertrophy on clinical outcomes remained significant when entered into multivariate analysis.
In line with animal studies, human newborns with CHD undergo obligatory age-related metabolic maturational changes that are modulated in the setting of hypertrophic response and can be responsible for worse peri-procedural outcomes.
Poster Sessions, Expo North
Saturday, March 09, 2013, 3:45 p.m.-4:30 p.m.
Session Title: Congenital Cardiology Solutions: Congenital Imaging
Abstract Category: 13. Congenital Cardiology Solutions: Pediatric
Presentation Number: 1160-123
- 2013 American College of Cardiology Foundation