P266DOCA/salt-induced hypertension + high-cholesterol/high-lipid diet

A large animal model of concentric LV hypertrophy with increased LV stiffness

Schwarzl, M.
Seiler, S.
Steendijk, P.
Huber, S.
Maechler, H.
Truschnig-Wilders, M.
Pieske, B.
Post, H.

¹Medical University of Graz, Department of Cardiology, Graz, Austria
²Leiden University Medical Center, Leiden, Netherlands
³Medical University of Graz, Department of Cardiac Surgery, Graz, Austria
⁴Medical University of Graz, Department of Laboratory Medicine, Graz, Austria

Cardiovascular Research 93(suppl_1):p S52-S87, March 15, 2012.

Background

Heart failure with preserved ejection fraction (HFPEF) is of increasing importance in the aging population. Although clearly associated with cardiac risk factors, the pathophysiology of HFPEF remains poorly understood, and pharmacological strategies established in systolic heart failure do not improve prognosis in HFPEF. This in turn is largely related to the lack of animal models for this disease.

Methods

Pigs were subjected to subcutaneous DOCA-pellet (deoxycorticosterone acetate, an aldosterone analogon) implantation and a high-lipid/high-salt feeding to mimick a cardiovascular risk profile of arterial hypertension and hyperlipidemia.

Results

After 3 months, DOCA-treated animals (n=3) versus time controls (n=3) developed persistent hypertension (tail-cuff systolic blood pressure during light sedation: 138 ± 5 vs. 93 ± 12 mmHg, p < 0.05) and had 8-fold increased plasma cholesterol levels. Echocardiography revealed concentric LV hypertrophy (septal wall thickness 16 ± 1 vs. 12 ± 1 mm, p < 0.05) at a preserved ejection fraction (72 ± 7 vs. 63 ± 10%, p=NS). LV pressure-volume analysis demonstrated a leftward shift and a steeper slope of end-diastolic pressure-volume relationships (EDPVR) compared to a weight- and age-matched historic control group (n=13).

Conclusion

We conclude that application of cardiovascular risk factors in pigs is able to induce a cardiac phenotype compatible with changes reported in human HFPEF. This model will serve for further mechanistic studies to decipher the haemodynamic and molecular pathophysiology of HFPEF.