Abstract 18307: Intracoronary Infusion of Allogeneic Cardiosphere Derived Cells, During Acute Myocardial Infarction Delays but Eventually Does Not Limit Remodeling of the Left Ventricle

Abstract

Objective: In animal models, it has been shown that myocardial cells regenerate even in the adult heart at very slow rates and that regeneration is stimulated after myocardial injury. However the endogenous mechanisms of regeneration are not adequate to limit the damage produced by an acute myocardial infarction.The objective of the study was to demonstrate if remodeling of the left ventricle is attenuated by intracoronary infusion of Allogeneic Cardiosphere Derived Cells (CDCs), at the ischemic phase of acute myocardial infarction, using a chronic ischemia- reperfusion model in swine. Method: In twelve pigs, AMI was induced by occlusion of Left Anterior Descending Coronary Artery for 60 minutes. At 60 minutes of ischemia, 6 animals received 5 million allogeneic CDCs (Group 1), and 6 (Group 2) normal saline, using a catheter that crossed the occlusion site. Five minutes after cell infusion, reperfusion was allowed. The follow up period was 30 days. All animals underwent transthoracic echocardiography before and immediately after the AMI, as well as at 15 and 30 days. Left ventricular end diastolic diameter (LVEDD), end-systolic diameter (LVESD) and ejection fraction (LVEF) were measured. Results: Group 1 animals did not demonstrate statistical significant increase in LV dimensions or decrease of EF at 15 days (LVEDD from 38mm to 42.6mm, p= 0.149, LVEF from 67.66% to 56.5%, p= 0.335). In contrast, Group 2 animals experienced significant decrease of LV function (LV EF from 56.5% to 48%, p=0.014) and a significant increase of LVESD (from 22.75mm to 28.5mm p=0.005) and LVEDD (from 32 mm to 37.75mm, p=0.009). However, animal in both groups had significant remodeling at 30 days There was an equivalent % reduction of LVEF (8.3% vs 7.6%, p=0.95) and increase of LVEDD and LVESD ( 6.5% vs 9.2 % p=0.3 and 6.3% vs 8.6% p=0.6 ,respectively) in Group 1 compared to Group 2. Conclusions: Infusion of allogeneic CDCs during acute AMI was safe and well tolerated hemodynamically, but produced only a transient benefit on LV function. This result may suggest that a re-infusion of cells is necessary at later time points after the index MI, in order to achieve sustained improvement.