title: Failure of right ventricular adaptation in children with tetralogy of Fallot.
abstract: BACKGROUND
  The left ventricle (LV) adapts to chronic hypoxia by expressing protective angiogenic, metabolic, and antioxidant genes to improve O2 delivery and energy production, and to minimize reoxygenation injury. The ability of the right ventricle (RV) to adapt to hypoxia in children with tetralogy of Fallot (TOF) is unknown.
  
  
  RESULTS
  Gene expression using real-time polymerase chain reaction was measured in RV myocardium obtained during surgical repair of TOF from 23 patients: 13 cyanotic and 10 acyanotic. Results were compared between the 2 groups and correlated with age at surgery, severity of cyanosis, and early postoperative course. The cyanotic patients were younger at surgery compared with acyanotic (5+/-3 versus 9+/-4 months; P=0.01), had higher hematocrit (43+/-4 versus 38+/-3 grams/dL; P=0.004), and lower O2 saturations (84+/-4% versus 98+/-2%; (P<0.001). Cyanotic patients had a significantly lower expression of vascular endothelial growth factor (VEGF), glycolytic enzymes, and glutathione peroxidase (GPX) (P<0.05), and a higher expression of collagen (P<0.01) compared with acyanotic patients. Gene expression correlated inversely with severity of cyanosis ie, preoperative hematocrit (P<0.01) and positively with preoperative saturation (P<0.05). The relationship between gene expression and cyanosis was independent of age at surgery. Ca2+ handling genes did not correlate with the severity of hypoxia. Lower angiogenic, glycolytic, and antioxidant gene expression correlated with increasing postoperative lactate (P<0.05).
  
  
  CONCLUSIONS
  The RV fails to up regulate adaptive pathways in response to increasing hypoxia in children with TOF. The implications of an early maladaptive response of the RV on long-term RV function require further investigation.
authors.affiliation: Division of Pediatric Cardiology, Department of Pediatrics, Columbia University, New York, NY, USA.
authors.forename: Sushma
authors.initials: S
authors.lastname: Reddy
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Osorio
authors.forename: Ana M
authors.initials: AM
authors.lastname: Duque
authors.forename: Beth D
authors.initials: BD
authors.lastname: Kaufman
authors.forename: Alistair B
authors.initials: AB
authors.lastname: Phillips
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Chen
authors.forename: Jan
authors.initials: J
authors.lastname: Quaegebeur
authors.forename: Ralph S
authors.initials: RS
authors.lastname: Mosca
authors.forename: Seema
authors.initials: S
authors.lastname: Mital
mesh_terms: D000222:Adaptation, Physiological; D000263:Adenylate Kinase / Q000096:biosynthesis / Q000235:genetics; D000367:Age Factors; D003094:Collagen / Q000096:biosynthesis / Q000235:genetics; D003199:Computer Systems; D064211:Connectin; D003490:Cyanosis; D004734:Energy Metabolism / Q000235:genetics; D005634:Fructose-Bisphosphate Aldolase / Q000096:biosynthesis / Q000235:genetics; D020869:Gene Expression Profiling; D005979:Glutathione Peroxidase / Q000096:biosynthesis / Q000235:genetics; D006019:Glycolysis / Q000235:genetics; D006352:Heart Ventricles / Q000378:metabolism / Q000503:physiopathology*; D006801:Humans; D000860:Hypoxia / Q000209:etiology / Q000235:genetics / Q000503:physiopathology; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000096:biosynthesis / Q000235:genetics; D007223:Infant; D009124:Muscle Proteins / Q000096:biosynthesis / Q000235:genetics; D015428:Myocardial Reperfusion Injury / Q000235:genetics / Q000517:prevention & control; D018919:Neovascularization, Physiologic / Q000235:genetics; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000235:genetics; D016133:Polymerase Chain Reaction; D011494:Protein Kinases / Q000096:biosynthesis / Q000235:genetics; D013771:Tetralogy of Fallot / Q000150:complications / Q000235:genetics / Q000503:physiopathology* / Q000601:surgery; D014157:Transcription Factors / Q000378:metabolism; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis / Q000235:genetics
chemical_list: D064211:Connectin; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009124:Muscle Proteins; C577285:TTN protein, human; D014157:Transcription Factors; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D003094:Collagen; D005979:Glutathione Peroxidase; D011494:Protein Kinases; D000263:Adenylate Kinase; D005634:Fructose-Bisphosphate Aldolase