Abstract 15763: Does the Stop-Flow Technique Improve Cardiac Retention of Intracoronarily Delivered Cells? A Study of Cardiac Retention of C-kit Positive Human Cardiac Stem Cells (hcscs) After Intracoronary Infusion in a Porcine Model of Chronic Ischemic Cardiomyopathy
Background: Cell based therapies have emerged as promising modalities in patients with ischemic cardiomyopathy, promoting reverse LV remodeling and improvement in cardiac function. It is commonly believed that the optimal methodology for intracoronary administration of cells is to stop coronary flow during cell infusion, in order to prolong cell/vascular wall contact, enhance adhesion, and promote extravasation of the cell product into the myocardium. Occlusion of a coronary artery with a balloon involves serious risks of vascular damage and/or dissection, particularly in non-stented coronary segments such as those commonly found in patients with heart failure. It remains unknown whether the use of the stop-flow technique results in improved cell engraftment. We addressed this issue in a clinically relevant model of chronic ischemic cardiomyopathy by directly comparing retention of hCSCs after intracoronary infusion with or without coronary occlusion.
Methods: Acute myocardial infarction was produced in 14 pigs by 90 minute intracoronary balloon inflation in the left anterior descending artery. One month later, pigs received 107 Indium-111 labeled c-kit positive hCSCs via intracoronary infusion with (n=7) or without (n=7) balloon inflation to stop flow. All pigs received cyclosporine to prevent acute graft rejection. Animals were euthanized 24 hours later and hearts taken for radioactivity measurements. These values were compared to the known initial radioactivity of the cell product (adjusted for decay and time dependent diffusive loss) to quantify cell retention.
Results: With the stop-flow technique, the retention of hCSCs at 24 h was 4.57±0.68% of the injected dose (n=7), compared with 4.12±0.53% without coronary occlusion (n=7)(P=0.58).
Conclusions: We conclude that when cells are delivered intracoronarily in a clinically relevant porcine model of chronic ischemic cardiomyopathy, the use of the stop-flow technique does not result in greater myocardial cell retention at 24 hours compared with non-occlusive infusion. These results have vital practical implications for the design of future trials of cell therapy. Our observations suggest that the increased risk of complications secondary to coronary occlusion is not warranted.
Author Disclosures: M.C. Keith: None. J.B. Elmore: None. X. Tang: None. Y. Tokita: None. A. Amraotkar: None. S. Ghafghazi: None. K.U. Hong: None. B.N. Vajravelu: None. M. Wysoczynski: None. J.B. Moore: None. G. Hunt: None. R. Bolli: None.
- © 2014 by American Heart Association, Inc.