2. Preclinical large-animal models of cardiovascular regeneration

The Centers for Disease Control estimates that about 5.7 million adults in the United States have heart failure (HF) and more than 550,000 new cases are diagnosed every year. The definitive treatment of end-stage HF remains orthotopic heart transplantation (OHT). The mortality rate while waiting for OHT is high (35% in 4 months) due to shortage of donor hearts. Prolonged wait periods also impose significant constraints on the health care system and patient quality of life. Despite recent advances in medical and device therapies, there are no effective long-term treatment strategies for heart attacks. To develop novel therapeutic approaches to improve blood flow to the heart, the scientific community has increasingly relied on preclinical large-animal models to test the feasibility of innovative treatments for cardiovascular regeneration. In this chapter, we provide an overview of the large-animal models available and the therapies being investigated and review the results obtained that pave the way for breakthrough treatment strategies, with a discussion on the hurdles that must be overcome for implementation in clinical trials.