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Development of Therapeutics for Heart Failure

Large Animal Models of Heart Failure

A Critical Link in the Translation of Basic Science to Clinical Practice

Jennifer A. Dixon, MD and Francis G. Spinale, MD, PhD

From the Division of Cardiothoracic Surgery, Medical University of South Carolina and Ralph H. Johnson Veterans Affairs Medical Center, Charleston, SC.

Correspondence to Francis G. Spinale, MD, PhD, Cardiothoracic Surgery, Strom Thurmond Research Center, 114 Doughty St, Suite 625, Charleston, SC 29425. E-mail wilburnm{at}musc.edu

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. Common pathophysiologic features of HF include changes in left ventricle structure, function, and neurohormonal activation. The recapitulation of the HF phenotype in large animal models can allow for the translation of basic science discoveries into clinical therapies. Models of myocardial infarction/ischemia, ischemic cardiomyopathy, ventricular pressure and volume overload, and pacing-induced dilated cardiomyopathy have been created in dogs, pigs, and sheep for the investigation of HF and potential therapies. Large animal models recapitulating the clinical HF phenotype and translating basic science to clinical applications have successfully traveled the journey from bench to bedside. Undoubtedly, large animal models of HF will continue to play a crucial role in the elucidation of biological pathways involved in HF and the development and refinement of HF therapies.

Key Words: myocardial infarction • myocardial remodeling • overload states • rapid pacing