Abstract-Congestive heart failure (HF) is a clinical syndrome, with hallmarks of fatigue and dyspnea, that continues to be highly prevalent and morbid. Because of the growing burden of HF as the population ages, the need to develop new pharmacological treatments and therapeutic interventions is of paramount importance. Key Words: myocardial infarction Ⅲ myocardial remodeling Ⅲ overload states Ⅲ rapid pacing C ongestive heart failure (HF) is a constellation of symptoms, with hallmarks of fatigue and dyspnea, which continues to be a highly prevalent and morbid clinical syndrome. Although the etiologic underpinnings of HF can be diverse, common pathophysiologic features include changes in left ventricle (LV) structure, function, and neurohormonal activation. The impact of HF will undoubtedly become even more substantial as the population ages. Accordingly, the need to develop new pharmacological treatments and therapeutic interventions for HF is of paramount importance. The journey from discovery, to understanding, to clinical application of the biological basis of HF is one that can only be traveled with the use of large animal models that recapitulate this clinical phenotype.The current pharmacological armamentarium in the treatment of HF includes angiotensin-converting enzyme inhibitors, aldosterone antagonists, and angiotensin and -adrenergic receptor blockade. 1 Although inhibition of the renin-angiotensin-aldosterone and sympathetic adrenergic systems have provided clear benefit to those suffering from HF, the disease process nonetheless continues. Therefore, further research is required to find additional pathways and mechanisms to target in the battle against HF.
The Need for Large Animal Models of HFSignificant insight into the molecular and cellular basis of cardiovascular biology has come from small animal models, particularly mice. However, significant differences exist with regard to cardiac characteristics such as heart rate, oxygen consumption, adrenergic receptor ratios, and response to loss of regulatory proteins, when mice are contrasted to humans. 2,3 Moreover, contractile protein expression, critical to the excitation-contraction coupling process, seems to differ between the 2 species, as evidenced by their differing predominant myosin isoforms. 2 Finally, evidence exists of significant phenotypic differences between mouse and human stem cells. 3 Consequently, extrapolation of murine systems, particularly after induction of cardiovascular stress, becomes problematic when making interpretations of human HF pathophysiology. Therefore, large animal models of HF, which more closely approximate human physiology, function, and anatomy, are essential to develop the discoveries from murine models into clinical therapies and interventions for HF.This review aims to summarize some of the more frequently used large animal models, which recapitulate the clinical HF phenotype arising from the common clinical etiologies of myocardial ischemia/infarction, ventricular overload states, and dilated cardiomyopath...
