Canine Model of Pacing-Induced Heart Failure

Abstract

Tachypacing-induced heart failure is a well-established large animal model that recapitulates numerous pathophysiological, structural and molecular features of dilated cardiomyopathy and, more in general, of end-stage congestive heart failure. The left or the right ventricle is instrumented with pacing electrodes to impose supernormal heart rates, usually three times higher than baseline values, for a length of time that typically ranges between 3 and 5 weeks. The animal of choice is the dog, although this protocol has been successfully implemented also in pigs, sheep, and rabbits. This chapter provides detailed methodology and description of the dog model utilized in our laboratory, which is one of the variants described in literature. Chronic instrumentation is completed by adding probes and catheters necessary to obtain measures of cardiac function and hemodynamics and to withdraw blood samples from various vascular districts. The progression from compensated to decompensated heart failure is highly reproducible, therefore, due also to the phylogenetic proximity of dogs to humans, tachypacing-induced heart failure is considered a highly clinically relevant model for testing the efficacy of novel pharmacological and nonpharmacological therapeutic agents. This model typically produces heart failure as defined by an LV dP/dt max <1500 mmHg/s, end-diastolic pressure >25 mmHg, mean arterial pressure <85 mmHg, and an ejection fraction <35%. One can expect a mortality rate of 5–10% due to fatal arrhythmias.