Induction and maintenance of an experimental model of severe cardiomyopathy with a novel protocol of rapid ventricular pacing

Abstract

Objective: An animal model of chronic severe heart failure is needed to evaluate new mechanical devices, surgical procedures, and medical therapies. The purpose of this study was to evaluate a unique new model of severe heart failure developed by means of a novel protocol of rapid ventricular pacing. Methods: Heart failure was induced in 8 mongrel dogs by means of rapid ventricular pacing (230 beats/min) for 4 weeks. After a sham operation, maintenance pacing at a reduced rate (190 beats/min) was continued for another 4 weeks. Results: Left ventricular systolic function was significantly reduced at week 4 and remained low at week 8, including the slope of the end-systolic pressure-volume relationship (2.4 ± 1.0 vs 0.7 ± 0.2 vs 0.8 ± 0.3 mm Hg/mL [baseline vs week 4 vs week 8, respectively]), ejection fraction (63% ± 5% vs 28% ± 7% vs 33% ± 5%), and cardiac output (3.1 ± 0.7 vs 2.0 ± 0.3 vs 2.2 ± 0.7 L/min). Significant ventricular remodeling changes took place with increased ventricular volumes and circumferential wall stress, which were stable between weeks 4 and 8. Serum catecholamine and atrial natriuretic polypeptide levels also increased from baseline but stabilized between weeks 4 and 8. The end-diastolic pressure-volume relationship also showed stable diastolic function between weeks 4 and 8. Conclusions: Induction pacing at 230 beats/min readily created severe heart failure in all animals, and a new technique of maintenance pacing provided a consistent model of severe heart failure. This model can be used to study a variety of new interventions for heart failure.