Establishing Chronic Stable Heart Failure in Ovine Model: Is It Feasible?

 

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Objectives: Various animal models have been described to create chronic heart failure (HF); however there are only few truly successful, reproducible models. Chronic stabile heart failure is particularly challenging in sheep model, which is known as best animal model for studies related to ventricular assist devices (VAD). In this animal study, we aimed to induce chronic stabile HF in ovine model using merely few transmural ligations of left coronary artery branches and avoiding ligation of main coronary arteries.

Methods: Ten ovines (mean weight 61 ± 7 kg) were operated on beating heart using left thoracotomy approach. Chronic HF is induced through ligations of the diagonal and marginal branches only. The pre-, intra- and post- operative hemodynamic and echocardiographic (echo) parameters were compared. The HF was defined by 20% increase in central venous pressure (CVP), heart rate (HR), pulmonary arterial pressure (PAP) and/or 20% reduction in the baseline cardiac output (CO) accompanied by echo findings of dilation of the left ventricle (LV) and 20% reduction in the left ventricular ejection fraction (LVEF).

Results: A total of (3 ± 1) coronary ligations were used. Merely one animal died intraoperatively due to severe heart failure. Another 2 animals died later due to hypoxia caused by early extubation and acute liver failure caused by worm infestation respectively. Seven animals survived the procedure and were followed up for (15 ± 4) days. Signs and symptoms of HF were observed in all animals at 8 ± 3 days and were treated with diuretic therapy. The mean arterial pressure, HR, mPAP, CVP and CO at baseline and prior to animal sacrifice were (78 ± 13 mm Hg) and (69 ± 21 mm Hg) p = 0.423; (73 ± 9 b/min) and (112 ± 23 b/min) p = 0.023; (15 ± 4 mm Hg) and (22 ± 3 mm Hg) p = 0.008; (11 ± 7 mm Hg) and (7 ± 2 mm Hg) p = 0.261; (3 ± 1 L/min) and (5 ± 0 L/min) p = 0.032 respectively. Meanwhile, repeated follow-up echos showed reduction in the LVEF and dilatation of LV. The LVEF at baseline and post ligation was 72 ± 13% and 31 ± 10% respectively (p = 0.033). The survived animals were supported with left VAD in a second procedure using right thoracotomy approach.

Conclusion: Establishing chronic stabile HF in ovine model is challenging but feasible. Clinical symptoms and drastic increase in the PAP and HR as well as echo findings were most sensitive parameters of HF. The CO per se is not a sensitive parameter. This chronic HF model was successfully used for studies related to VAD.