The applicant is medically trained with future aspirations to establish his own internationally renowned ‘bench to bedside’ research laboratory. He has previous research experience and particular interest in unravelling the mechanisms of cardiovascular disease, which accounts for 1 in 3 deaths in New Zealand. The present study will investigate a type of heart failure in which the pumping function of the heart is normal at rest but fails on exercise (heart failure with preserved ejection fraction (HFpEF)). HFpEF is increasing in prevalence in the young and ageing (more than one-third of all heart failure), causing profound breathlessness and fatigue, but it has no known beneficial treatments. After fully characterising a large animal model of HFpEF, which allows more invasive and detailed investigations, this study will seek to determine the cause(s) for this type of heart failure and to explore the effectiveness of a novel drug to treat it.