Advancing Novel Treatments to Improve Outcomes from Cardiac Arrest & Resuscitation

Unlike a heart attack, cardiac arrests (CA) are almost always fatal. Of the 25,000+ Australians (male and female) who experience CA each year, as few as 5 % survive to go home, and up to 60 % of these survivors will still suffer from debilitating brain injury. Adrenaline (epinephrine) administration during CA resuscitation has been recommended by international guidelines since the 1960s, and its use consistently improves short-term recovery of an arrested heartbeat. However, increasing evidence has shown that epinephrine use does not affect CA survival and may dramatically increase the likelihood of severe neurological impairment long-term (compared to placebo). This project, led by the Head of the Preclinical Cardiology Research Platform at the Baker Institute and the Head of Cardiology at the Alfred Hospital, uses state-of-the-art technologies to re-examine this standard practice with a critically needed investigation into potential consequences of epinephrine use during CA resuscitation, and evaluation of new therapies. Our department have established a novel model of cardiac arrest with cardiopulmonary resuscitation in the mouse (Donner et al., Resus Plus, 2022), alongside industry-leading expertise in the use of high resolution echocardiography, cardiac MRI and invasive haemodynamics technologies (et al.) to comprehensively evaluate outcomes following CA in mice. This project (or each of its parts) would be well-suited to a BMedSci, Honours, Masters or PhD student. Part 1): To investigate the impact of epinephrine use during CA resuscitation on cardiovascular and neurological injury and dysfunction. Part 2): To compare the impact and mechanisms of epinephrine use between males and females; and with sex hormone disruption/decline. Part 3): To evaluate and compare the safety and efficacy of novel therapies to replace or combine with epinephrine for CA resuscitation in males and females. By understanding the impact of epinephrine and other novel therapies on cardiac arrest-induced injury and subsequent disease, this work will inform strategies for clinical translation of new treatments and potential refinements of current standard practice.