The identification of contributory mechanisms for the development and progression of congestive heart failure in animal models.

Congestive heart failure is a clinical syndrome which results from left ventricular pump dysfunction. Animal models of congestive heart failure have been developed to better understand the complex mechanisms which contribute to the clinical syndrome of heart failure. The species and lesions used to create chronic left ventricular dysfunction in animals are as varied as the etiologic factors which cause congestive heart failure in human beings. However, a central issue to the animal models of congestive heart failure is how closely they mimic the human syndrome of congestive heart failure. The findings derived from the study of an animal model of left ventricular dysfunction should be carefully interpreted, keeping in mind the complexity of the human disease process. With careful interpretation of the results, important insights into the pathogenesis of congestive heart failure in patients can be realized. For example, the rat coronary artery ligation model provided fundamental information on the role of the angiotensin-converting enzyme system on left ventricular function and survival. Chronic pressure and volume overload, as well as rate overdrive (rapid pacing), models have provided temporal and mechanistic information on left ventricular remodeling and the transition to left ventricular dysfunction and, subsequently, congestive heart failure. Preclinical studies using animal models of heart failure are needed to investigate the effects of pharmacologic interventions in the progression of congestive heart failure. Animal models which have been produced with specific gene product deletions or over-expression will increase our ability to identify potential contributory mechanisms for the progression of left ventricular dysfunction. Animal models of congestive heart failure are clearly helpful to define the mechanisms responsible for this syndrome and to develop effective strategies to slow or better reverse its progress.