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(Circulation. 2006;114:I-37 – I-42.)
© 2006 American Heart Association, Inc.

Cardiac Transplantation and Surgery for Congestive Heart Failure

Failure of Right Ventricular Adaptation in Children With Tetralogy of Fallot

Sushma Reddy, MD; Juan Carlos Osorio, MD; Ana M. Duque, MD; Beth D. Kaufman, MD; Alistair B. Phillips, MD; Jonathan M. Chen, MD; Jan Quaegebeur, MD, PhD; Ralph S. Mosca, MD; Seema Mital, MD

From the Division of Pediatric Cardiology (S.R., J.C.O., A.M.D., B.D.K., S.M.) and Cardiothoracic Surgery (A.B.P., J.M.C., J.Q., R.S.M.), Department of Pediatrics, Columbia University, New York, NY.

Correspondence to Seema Mital, Morgan-Stanley Children’s Hospital of New York Presbyterian, 2 North, Suite 221 N, 3959 Broadway, New York, NY 10032. E-mail sm364{at}columbia.edu

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.

Methods and 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.

Key Words: gene expression • hypoxia • right ventricle • tetralogy of Fallot