A lack of preclinical large animal models of heart failure with preserved ejection fraction (HFpEF) that recapitulate this comorbid-laden syndrome has led to the inability to tease out mechanistic insights and to test novel therapeutic strategies. This study developed a large animal model that integrated multiple comorbid determinants of HFpEF in a miniswine breed that exhibited sensitivity to obesity, metabolic syndrome, and vascular disease with overt clinical signs of heart failure. The combination of a Western diet and 11-deoxycorticosterone acetate salt-induced hypertension in the Göttingen miniswine led to the development of a novel large animal model of HFpEF that exhibited multiorgan involvement and a full spectrum of comorbidities associated with human HFpEF.
Keywords: DBP, diastolic blood pressure; DOCA, 11-deoxycorticosterone acetate; EC50, half-maximal effective concentration; EF, ejection fraction; HDL, high-density lipoprotein; HFpEF, heart failure with preserved ejection fraction; HFrEF, heart failure with reduced ejection fraction; IVGTT, intravenous glucose tolerance test; LDL, low-density lipoprotein; LV, left ventricle; PCWP, pulmonary capillary wedge pressure; SBP, systolic blood pressure; TC, total cholesterol; WD, Western diet; animal models of human disease; heart failure with preserved ejection fraction; hypertension; metabolic syndrome; obesity.
© 2021 The Authors.