Project summary
Understanding the role of the intrinsic cardiac nervous system in myocardial ischaemia (decreased blood flow and oxygen to the heart muscle) and arrhythmias.
What is the issue for NSW?
The heart is innervated by a network of nerves (intrinsic cardiac ganglion neurons) that modulates heart rhythm and force of contraction. This network interposes between the brain and the heart, influencing the reciprocal signalling between both organs. There is compelling evidence that this network of nerves can trigger serious arrhythmias and affect survival in a range of cardiac diseases from coronary heart disease through to single gene disorders.
What does the research aim to do and how?
At present, we have a limited understanding of how these nerves communicate with each other and with the heart, and we only have crude methods (e.g. nerve ablation) to deal with malfunction of intrinsic cardiac nerves. This project will study ion channels and receptors, membrane proteins that are responsible for the molecular mechanisms by which nerves communicate, to help design better treatments.
Over 400 distinct ion channels and receptors have been identified to date, and changes in their expression and function can lead to the manifestation of various diseases including in the cardiovascular system. Thus, modification of pathological cardiac function through ion channels expressed in the intrinsic cardiac nervous system is a plausible therapeutic strategy demanding development.
The intra-cardiac neuronal network is linked to various cardiac diseases, including heart attack, angina, nerve damage caused by diabetes and the infectious Chagas disease. In the context of heart attack, changes to intra-cardiac nerves during healing of the heart can often produce fatal arrhythmias.
Professor Adams’ laboratory has developed techniques that allow an innovative approach to understanding the abnormal electrical behaviour of these nerves, including the ability to prepare and study whole mammalian intrinsic cardiac ganglion. These techniques can precisely guide the development of novel therapies or repurposing currently available drugs for novel therapeutic interventions.
The proposed research seeks to better understand intrinsic cardiac neurotransmission as a prerequisite to the development of new therapeutic approaches for treating common, serious life-threatening cardiovascular conditions. This research will help build capacity in cardiovascular disease research in NSW with emphasis on those conditions associated with atrial fibrillation and cardiac arrhythmias.