Methods for the development and assessment of atrial fibrillation and heart failure dog models

OBJECTIVE To report Medtronic experiences with the development of animal models for atrial fibrillation (AF) and chronic heart failure (CHF) using high-rate pacing for AF and microemboli for CHF. METHODS For the AF model, an atrial lead was attached to a Medtronic Synergy™ neurostimulator, which was programmed to stimulate at 50 Hz in an on-off duty cycle. Atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and N-terminal pro brain natriuretic peptide (NT-proBNP) were assayed at select time points. For CHF model, a serial injection of 90 µm polystyrene microspheres at 62,400 beads/mL (Polybead, Polysciences, Inc.) was performed to induce global ischemia, either with weekly monitoring and embolization schedule (group 1, n = 25) or with biweekly monitoring and emboliation schedule (group 2, n = 36 ). Echocardiograms were used along with ventriculograms and magnetic resonance imaging scans weekly to assess cardiac function and ANP, BNP and NT-proBNP were monitored. RESULTS For the AF model, the days to sustained AF for four animals following surgery were 7, 25, 21 and 19, respectively; For the CHF model, the days to meet CHF endpoints were 116 in group 1 and 89 in group 2. For both AF and CHF models, NT-proBNP correlated well with the development of disease states. CONCLUSION Our experience for the development and assessment of AF and CHF dog models may help researchers who are in search for animal model for assessing the safety and efficacy of a device-based therapy.