Abstract 337: Long Term Safety and Efficacy of a Cardiac Graft in a Swine Model of Heart Failure

Abstract

Introduction: We have shown efficacy with cardiac grafts in the rat coronary ligation model of chronic heart failure (CHF) and feasibility of implantation and assessment in a swine model. Now we propose testing its long term safety and efficacy in a swine model of CHF. Our aims are: 1) Evaluate long term (6 months) left ventricular functional improvements after implantation of the graft in a swine coronary artery occlusion model of CHF, 2) Evaluate quality of life and functional capacity improvements of swine treated with the graft, and 3) Evaluate long term safety of the graft. Hypothesis: An engineered tissue comprised of differentiated cardiac myocytes and fibroblasts will effectively integrate into the host tissue, and restore cardiac function in swine with CHF. Methods: Male Yucatan mini swine 30-40kg were infarcted using percutaneous methods. Balloon occlusions (90 minute) are performed via catheter, distal to the first diagonal branch of the left anterior descending (LAD) coronary artery and animals. Four weeks after myocardial infarction (MI) cardiac grafts engineered with bio absorbable knitted mesh are implanted on the infarcted epicardium. Cardiac magnetic resonance imaging (MRI) is performed prior to MI, 1 month after MI, 1 month after patch placement, again at 3 month and 6 months. All swine are implanted with continuous event recorders to acquire surface electrocardiogram during the entire study. In addition, quality of life/functional capacity are assessed using FitBark collar activity monitors and treadmill exertion testing. Infarct size is determined using MRI images and 2,3,5-triphenyltetrazolium chloride staining at study end. Results: Medium to large transmural infarcts are generated with 90min balloon occlusion of the LAD which demonstrate compensatory remodeling of the LV as assessed via cardiac MRI. Upscale cardiac matrix grafts to 6cm diameter are easily handled by the surgeon and can be surgically implanted on the epicardium using sub-xiphoid median sternotomy. No adverse arrhythmic activity has been observed. Conclusion: Our cardiac graft is well suited for upscale to clinical size, can be easily handled and implanted in a swine model of CHF.