Cardiovascular disease is the main cause of death in the UK and throughout the Western World. Around half of these are caused by an unexpected change in the rhythm of the heart leading to collapse and cardiac arrest, known as "sudden cardiac death." The most common trigger for this is a heart attack, which occurs when one of the heart's arteries is blocked. However, why some heart attacks trigger dangerous heart rhythms and others do not is not fully understood.
Introduced over 50 years ago, drugs called beta-blockers stop the action of a stress hormone called norepinephrine, and are currently the only drugs that prolong life after a heart attack by helping to prevent dangerous heart rhythms. In new research from the Herring Group, it is hypothesised that an additional stress hormone called Neuropeptide-Y (NPY) may be a key trigger for dangerous heart rhythms. The team previously demonstrated that levels of NPY are very high during a heart attack in an earlier paper published in June 2019.
To test this hypothesis, a new study led by Associate Professor Neil Herring and funded by the British Heart Foundation uses a combination of data from patients being treated for heart attacks as part of the Oxford Acute Myocardial Infarction (OxAMI) Study in collaboration with Professor Keith Channon at the Oxford Heart Centre and the Radcliffe Department of Medicine, alongside molecular work and animal studies performed in DPAG and in collaboration with Dr Ajijola and Dr Shivkumar at UCLA Health. The study employs a novel imaging technique where combinations of fluorescent dyes are used to visualise the effects of nerve stimulation on the electrical and metabolic activity of the heart.
In patients undergoing emergency treatment for large heart attacks, researchers demonstrated that the levels of NPY measured in conventional blood samples are associated with the occurrence of life threatening heart rhythms (ventricular arrhythmias) despite patients being treated with beta-blockers. Using an animal model and human tissue, the team found that this stress hormone is released from nerves supplying the heart and acts on heart cells via a specific receptor, Y1, to upset their balance and cause uncoordinated contraction. Critically, in an experimental heart attack model, researchers show that blockers of this receptor can help prevent dangerous rhythms. According to Prof Herring, "drugs targeting this receptor may therefore provide a useful new way to save lives after a heart attack, although more research is needed to establish this in patients."
The full paper, The cardiac sympathetic co-transmitter neuropeptide Y is pro-arrhythmic following ST-elevation myocardial infarction despite beta-blockade, is available to read on the European Heart Journal Website.