Figure 1.

Experimental Protocol of a Novel Multihit Minipig Model of HFpEF

Female Göttingen minipigs were subjected to 20 weeks of excess mineralocorticoid exposure and dietary insults to drive development of prominent comorbidities associated with heart failure with preserved ejection fraction (HFpEF): obesity, hypercholesterolemia, pre-diabetes, and pulmonary and systemic arterial hypertension. Adult female Göttingen miniswine were randomized to the control group (n = 3) and fed a standard diet or to the HFpEF group (n = 5) and received subcutaneous implantation of deoxycorticosterone acetate (DOCA) pellets (50 mg/kg, 60-day release) and fed a custom Western diet high in cholesterol (1%), fat (21%), fructose (8.9%), and salt (2%). Body weights, circulating lipid levels, and transthoracic echocardiographic assessment of cardiac function and structure were evaluated at baseline and at 4, 8, 12, 16, and 20 weeks. Intravenous glucose tolerance testing and invasive hemodynamics were performed at baseline and at 20 weeks. At 20 weeks, hearts, lungs, liver and kidneys were collected, coronary arteries isolated for ex vivo vascular reactivity experiments, and histological tissue fibrosis quantified in left ventricular myocardium and renal cortex samples.