Characterization of cardiac remodeling in a large animal "one-kidney, one-clip" hypertensive model.

OBJECTIVE: The aim of this study is to characterize cardiac remodeling in a large animal model of hypertension. METHODS: 23 sheep were subjected to unilateral nephrectomy followed by clamping of the remaining renal artery to 60% ("one kidney-one clip", 1K1C) 3 weeks later. Blood pressure (BP) was monitored invasively over 73+/-28 days. Cardiac function was assessed with magnetic resonance imaging and compared with 12 size-matched controls. Detailed atrial histopathological analysis was performed. RESULTS: In the 1K1C animals, BP rose from baseline to reach a plateau by 4 weeks (systolic BP: 107+/-12 to 169+/-27, diastolic BP: 71+/-10 to 118+/-29 mmHg, both p< 0.0001); cardiac hypertrophy was significant when compared with controls with increased left ventricular weight [left ventricular (LV)/body wt: 2.7+/-0.5 vs 2.1+/-0.2 g/kg, p=0.01] as well as bi-atrial enlargement (right atrial, RA: 22.9+/-4.9 vs 15.7+/-2.8g, p=0.003; left atrial, LA: 35.5+/-6.7 vs 20.9+/-4.1g, p=0.0003); cardiac magnetic imaging demonstrated significantly increased LA volumes (end-diastolic volume: 42.9+/-6.8 vs 28.7+/-6.3 ml, p< 0.0001) and reduced LA ejection fraction (24.1+/-3.6 vs 31.6+/-3.0%, p=0.001) while LV function was relatively preserved (42.3+/-4.7 vs 46.4+/-4.1%, p=0.1); degeneration and necrosis of atrial myocytes were evident with increased atrial lymphocytic infiltration and interstitial fibrosis. CONCLUSIONS: The ovine 1K1C model produces reliable and reproducible hypertension with demonstrable cardiac end-organ damage.