Small Animal Models of Heart Failure

Abstract

Received June 23, 2008; accepted January 20, 2009. The study of heart failure requires viable animal models whereby chronic changes in myocardial structure and function can evolve and the progression of heart failure and left ventricular (LV) dysfunction can be quantified. During the past 40 years, basic and translational scientists have used small animal models to explore the pathophysiology of heart failure and to develop novel therapies that might slow the progression of this prevalent and fatal disease. The purpose of this review is to describe commonly used heart failure models in rodents and to cite examples of how these models have been used to evaluate novel therapies for the treatment of heart failure. Heart failure models were originally developed in rats because of numerous potential advantages inherent in a small animal model (see Table 1). Housing and maintenance costs for rats are much lower than for large animals, thus reducing costs and increasing the number of animals included in a given study to improve the statistical power. Moreover, more recent technological advances in echocardiography, MRI, and micromanometer conductance catheters have greatly streamlined the assessment of cardiac function in rodents, removing a significant barrier to their use in heart failure research. The development of suitable expertise to perform open-chest surgical procedures and invasive hemodynamic assessments in rats is far easier compared with that required for mice. Additionally, investigators are able to perform a greater number of postmortem histological or molecular biological analyses given the approximately 10-fold greater myocardial mass of rats compared with mice. For these reasons, the rat models detailed below have been the most widely and successfully used heart failure models in basic and translational research. View this table: Table. Commonly Used Rodent Heart Failure Models Myocardial infarctions (MIs) in rats were originally induced by the sequential administration of subcutaneous isoproterenol …