Neurocardiovascular Physiology Group

Vagal nerve stimulation (VNS) has enormous therapeutic potential as evidenced by ~200 current clinical trials assessing its therapeutic potential across multiple diseases (Clinicaltrials.gov). However, it is plagued by disabling side effects, such as cough and neck pain, and substantial variability in efficacy between subjects and within subjects over time. This is due to multiple factors, including that the: (i) vagus nerve is not homogeneous, containing both motor and sensory nerve axons, (ii) the anatomy of the vagus nerve is not consistent between people such that electrode placement affects which axons are stimulated and (iii) understanding of which axon groups need to be stimulated for effective therapy in different conditions remains poor. There is an urgent need for a greater understanding of the organisation of the components of the vagus nerve to increase efficacy. We are addressing these issues using cutting-edge optogenetic methods to specifically target efferent vagal fibres (the hardest fibre type to target electrically) in diseases, such as heart failure.

Approximately 2 million cardiac surgical procedures requiring cardiopulmonary bypass (CPB) are performed annually worldwide¹ and a major unresolved clinical complications arising from CPB is postoperative delirium.^{2, 3} It occurs in ~50% of patients and these patients have a >30% risk of developing long-term cognitive decline with dementia after 7.5 years.² There is emerging evidence that one of the critical drivers of delirium after CPB is neuroinflammation.³ In close collaboration with the Translational Cardiovascular and Renal Research Group, we are determining how CPB drives neuroinflammation and investigating novel treatments targeting neuroinflammation.

^1. Hu J et al. J Cardiothorac Vasc Anesth. 2016;30:82-9.

^2. Greaves D et al. International journal of cardiology. 2019;289:43-49.

^3. Jufar AH et al. Acta physiologica (Oxford, England). 2022;236:e13860.