RESEARCH ARTICLE Identification of Region-Specific Myocardial Gene Expression Patterns in a Chronic Swine Model of Repaired Tetralogy of Fallot

Surgical repair of Tetralogy of Fallot (TOF) is highly successful but may be complicated in adulthood by arrhythmias, sudden death, and right ventricular or biventricular dysfunction. To better understand the molecular and cellular mechanisms of these delayed cardiac events, a chronic animal model of postoperative TOF was studied using microarrays to per-form cardiac transcriptomic studies. The experimental study included 12 piglets (7 rTOF and 5 controls) that underwent surgery at age 2 months and were further studied after 23 (+/- 1) weeks of postoperative recovery. Two distinct regions (endocardium and epicardium) from both ventricles were analyzed. Expression levels from each localization were com-pared in order to decipher mechanisms and signaling pathways leading to ventricular dys-function and arrhythmias in surgically repaired TOF. Several genes were confirmed to participate in ventricular remodeling and cardiac failure and some new candidate genes were described. In particular, these data pointed out FRZB as a heart failure marker. More-over, calcium handling and contractile function genes (SLN, ACTC1, PLCD4, PLCZ), poten-tial arrhythmia-related genes (MYO5B, KCNA5), and cytoskeleton and cellula