Uncovering the interaction of obstructive sleep apnoea with cardiac metabolism, function, and disease

Working with Dr Melissa Farnham and Dr Kristina Cook, we have recently uncovered that intermittent hypoxia (as seen in obstructive sleep apnoea) causes hallmarks of cardiac insulin resistance and changes in cardiac substrate utilisation such as upregulation of cardiac ketone bodies. We have developed a program that includes homes sleep studies in all our heart failure patients (with Prof Peter Cistulli, ResMed Chair in Sleep Medicine), a lab model of intermittent hypoxia (Dr Melissa Farnham, HRI), with expertise in the master regulator of hypoxia transcriptional change, HIF-1α (Dr Kristina Cook, Charles Perkins Centre).

We aim to do the following:

1. Determine the mechanisms of intermittent hypoxia-induced metabolic dysregulation via HIF-1α and other regulators.
2. Develop novel therapeutics to mitigate these effects.
3. Explore the cardiovascular perturbations consequent upon these changes.
4. Examine the metabolic and cardiovascular consequences of obstructive sleep apnoea clinically using our advanced echocardiography, vascular measurements, cardiac MRI, and sophisticated metabolic profiling.

Outcomes:

1. The first rigorous exploration of the protean cardiometabolic changes induced by obstructive sleep apnoea.
2. Novel management strategies and therapeutic agents to target these cardiometabolic complications.