Abstract
Background and AimsIn human adults, and animals, the Apelin-APJ ligand-receptor system is emerging as having a role in the pathogenesis of cardiovascular function and heart failure. The aim was to investigate expression, and regulation by oxygen, of the Apelin APJ receptor (APJ) in myocardium obtained from children undergoing corrective surgery with cardiopulmonary bypass for repair of congenital heart defects.MethodsWestern blotting and Real-time PCR were used to determine if APJ was expressed in the infant myocardium, if expression was influenced by the duration of myocardial ischemia and if any relationship existed between APJ expression and early post-operative outcome. The next aim was to determine if there was a difference in mRNA expression of APJ in myocardium from cyanotic patients compared with acyanotic patients and if re-perfusing myocardium in vitro with either hypoxic, normoxic or hyperoxic oxygen affected APJ mRNA expression.ResultsAPJ was expressed in all myocardial samples and myocardium exposed to longer durations of ischemia and cardioplegia expressed higher levels of APJ (p<0.05). There was a significant correlation between APJ expression in myocardium resected after 10 min with both oxygen extraction ratio (p = 0.021, rho = −0.523) and mixed venous oxygen saturation (p = 0.028, rho 0.52). This association did not exist for myocardium collected before 10 min. There was no difference in APJ expression between cyanotic and acyanotic patients. No difference was found in APJ expression whether re-perfused with low, normal or high oxygen.ConclusionsChanges in APJ expression were observed during cardiopulmonary bypass in children and the reasons for this require further investigation.
Highlights
Tetralogy of Fallot (TOF) is the most common cyanotic congenital heart disease
TOF is characterized by the presence of ventricular septal defect, pulmonary stenosis, aortic over-ride and right ventricular hypertrophy
Western Blot Analysis To date the APJ receptor has not been identified in the infant myocardium
Summary
Tetralogy of Fallot (TOF) is the most common cyanotic congenital heart disease. TOF is characterized by the presence of ventricular septal defect, pulmonary stenosis, aortic over-ride and right ventricular hypertrophy. Post-operative right ventricle (RV) dysfunction is common and impacts on early patient outcome. In the decades that follow TOF repair continuing RV dilation and dysfunction can limit exercise capacity and life expectancy. The etiology of RV dysfunction post TOF correction is multifactorial. Prior to surgery the RV myocardium is perfused with blood of reduced oxygen content (cyanosis) and the ventricle is pressure loaded due to the presence of the VSD. The aim was to investigate expression, and regulation by oxygen, of the Apelin APJ receptor (APJ) in myocardium obtained from children undergoing corrective surgery with cardiopulmonary bypass for repair of congenital heart defects
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