A refined approach of the tachypacing porcine model of heart failure

Abstract

Background: Preclinical models of heart failure (HF) play a key role in developing new therapeutic strategies. Tachypacing is the gold standard to induce dilated cardiomyopathy (DCM) with reduced ejection fraction (EF) in large animals, but it is not exempted from failures and can induce relevant stress. Aim: Establishing a revised porcine model of tachypacing-induced HF to improve reliability and reduce stress on the animals. Methods: Eight (n=8) females Göttingen minipigs were divided in two groups: 4 animals were implanted a right ventricular two-lead pacemaker to induce HF via tachypacing, while 4 animals without implant served as controls. After a recovery period, pigs were paced asynchronously at 180bpm for 2-weeks and 200bpm for 4-weeks. Disease progression was assessed by echocardiography, while hemodynamics was measured invasively before sacrifice. Stress was evaluated by jacketed external telemetry (JET), cortisol, body weight, and clinical symptoms. Results: Echocardiographic assessment showed that all paced animals developed stable DCM as demonstrated by increase of end-systolic and end-diastolic volume at highly depressed ejection fraction. Invasive measurements confirmed these results with stable mAOP despite impaired pump function. JET showed no alterations of respiratory rate and daily activity throughout the protocol. Cortisol and cortisone levels and body weight showed no significant differences between groups or during pacing. Conclusions: We established a reliable model of tachypacing-induced HF based on slower pacing and milder progression to HF, while reducing the stress and suffering of the animals.