In cyanotic patients undergoing repair of heart defects, cyanosis (chronic hypoxia) is thought to lead to greater susceptibility to ischaemia and reoxygenation injury. Using gene expression profiling in heart tissue from cyanotic and normoxic patients, we recently showed that cyanosis alters apoptosis signalling and MAPK pathway transcripts (Ghorbel et al., 2010). However, it is not known whether changes in genes expression are also associated with changes in protein expression. The aim of this study is to investigate the effect of cyanosis on the protein expression of apoptosis and cell survival markers in human myocardium. Right ventricular biopsies were obtained from 10 months old paediatric patients undergoing corrective surgery for cyanotic (Tetralogy of Fallot) and acyanotic pathologies (n=6 for each group). This work has ethical approval and all patients’ guardians gave consent. Western blotting of HIF1alpha showed a significant up regulation in cyanotic compared to acyanotic tissue confirming the hypoxic state this patient group suffer from. Additionally, there was a significant increase of cleaved-caspase 3 (activated form) and BAX protein expressions in cyanotic compared to acyanotic myocardium. Caspase-3 is a critical apoptosis executioner and BAX is a well-documented apoptotic activator. Increased levels of cleaved-caspase 3 and BAX in cyanotic paediatric myocardium indicate an increased apoptosis activity in the heart of these patients. Cyanosis was found to alter survival signalling associated with MAPK pathway. This was demonstrated by a significant decrease of Phosphorylated-SAPK (activated form) expression level in cyanotic compared to acyanotic myocardium. There was also a tendency to decrease in phosphorylated-ERK in cyanotic myocardium. This data suggest that chronic hypoxia (cyanosis) triggers apoptosis and reduces pro-survival signalling in the myocardium of paediatric patients. These changes along with the effects of reoxygenation injury could explain the higher cardiac injury seen in cyanotic patients compared to normoxic patients undergoing open heart surgery.