Animal models of dilated cardiomyopathy for translational research

Abstract

Animal models of cardiovascular disease have proved critically important for the discovery of pathophysiological mechanisms and for the advancement of diagnosis and therapy. They offer a number of advantages, principally the availability of adequate healthy controls and the absence of confounding factors such as marked differences in age, concomitant pathologies and pharmacological treatments. Dilated cardiomyopathy (DCM) is the third cause of heart failure (HF) and is characterized by progressive ventricular dilation and functional impairment in the absence of coronary lesions and/or hypertension. Over the past thirty years, investigators have developed numerous small and large animal models to study this very complex syndrome. Genetically modified mice are the most widely and intensively utilized research animals and allow high throughput studies on DCM. However, to translate discoveries from basic science into medical applications, research in large animal models becomes a necessary step. An accurate large animal model of DCM is pacing-induced HF. It is obtained by continuous cardiac pacing at a frequency three- to fourfold higher than the spontaneous heart rate and is mostly applied to dogs, but also to pigs, sheep and monkeys. To date, this model can still be considered a gold standard in HF research.