Large animal models of congestive heart failure: A critical step in translating basic observations into clinical applications

Congestive heart failure (CHF) is a clinical syndrome in which pathophysiologic underpinnings include left ventricular (LV) dysfunction, remodeling, and increased neurohormonal activation. Accordingly, large animal constructs must be developed that mimic this disease process in order to define new pharmacologic and surgical treatment strategies. Multiple large animal species have been used for these purposes. For instance, canine coronary artery microembolization has been used to generate ischemia-induced LV dilation and dysfunction. Sheep have been subjected to total acute coronary artery occlusion to evaluate ischemia-induced mitral valve insufficiency. Rapid ventricular pacing has been used in both dogs and pigs to reproduce the characteristics of dilated cardiomyopathy. Each model is associated with advantages and disadvantages. Therefore findings derived from the study of large animal models of LV failure must be carefully evaluated. With proper interpretation, important insights into the pathogenesis of CHF may be realized. Furthermore, these models may be used in conjunction with imaging modalities such as magnetic resonance imaging, single photon emission computed tomography, and positron emission tomography to elucidate the identification of cellular and extracellular alterations associated with LV failure. Thus large animal models of CHF are critical components in the effort to translate basic observations into beneficial clinical applications.