Developmental Programming of Cardiac Arrhythmia

Sustained ventricular arrhythmias are a major cause of sudden cardiac death in the UK and Western world. Treatment of these conditions is challenging because the origin of ventricular arrhythmias is often unrecognised until the person dies.  Genetics, lifestyle choices and environmental factors, such as diet and air pollution, undoubtedly contribute to the origin and penetrance of ventricular arrhythmic disorders. However, to our knowledge, no studies have considered the role of the intrauterine environment during pregnancy.

The seminal work from Barker in the 1980’s demonstrated that adverse events during pregnancy are strongly correlated with heart disease in offspring during adulthood. Since then, numerous maternal factors and pathologies have been linked with offspring cardiovascular disease, including preeclampsia, obesity and gestational diabetes. Importantly, we have shown that oxygen deprivation during fetal development increases ventricular arrhythmia susceptibility in adulthood. This discovery suggests that some cardiac arrhythmias may have a developmental origin, and it provides us with a unique opportunity to intervene and prevent the risk of arrhythmia in adulthood even before a person is born. In this interventional project, we integrate radiotelemetry, cardiac optical mapping and fluorescence microscopy to understand the mechanisms driving arrhythmia susceptibility in offspring from hypoxic pregnancies, and we are developing a maternal antioxidant therapy to protect against it.