Abstract
Background: The failure of the development of treatment for HFpEF is the result of key factors: critically, HFpEF is a disease of ageing in combination with other factors including atrial fibrillation, and the effect of potential treatments for HFpEF can only be validated pre-clinically in-vivo using large animal models, to effectively prove effects on heart function. Aim: To characterise a large animal model of HFpEF and determine applicability for pre-clinical therapeutic research. Methods: Eight aged and eight young female sheep (ewes) were anaesthetised and underwent transthoracic echocardiography and were instrumented with a left ventricular pressure transducer catheter. Left ventricular biopsies were taken for histological and molecular analysis. Results: Sheep (ewes) aged >6yrs had a preserved LVEF 73 ±8% vs young, with marked LV hypertrophy, significant myocardial fibrosis compared to young animals and elevated LVEDP (aged: 10.3 ± 1.5 vs young: 3.8 ± 0.9 mmHg, p<0.05). Conclusions: This acute study has characterised a clinically relevant, large animal model of HFpEF.
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