Abstract

Background: Since the first intracoronary delivery of cells to the heart in 2001, the stop-flow technique has been used by default. A balloon angioplasty catheter is inflated in the target vessel and cells infused via the luminal port. However, the need for balloon occlusion has never been demonstrated. Objective: We sought to compare the safety and efficacy of intracoronary delivery of allogeneic cardiosphere derived cells (CDCs) under stop-flow versus nonocclusive intracoronary delivery in a porcine model of myocardial infarction (MI). Methods: MI was created by 2.5 hr occlusion of the mid-LAD in adult female Yucatan minipigs. Three weeks later, 12.5M CDCs were intracoronarily infused in the LAD under stop-flow (in 3 3-min occlusions with 3 min rest intervals) or nonocclusive conditions (continuous-flow infusion over 10 min; n=5 in each group). During the course of the study, animals underwent contrast enhanced magnetic resonance imaging at baseline (just before infusion) and 4 weeks post infusion. Left ventricular ejection fraction, scar mass and viable mass were evaluated at both time points. Results: No adverse events (arrhythmias, death) were observed during or soon after cell infusion in any of the animals infused. Coronary blood flow evaluated by TIMI grade was TIMI 3 in all animals following completion of infusion. TnI and CK-MB values were within normal range 1 day post-infusion in all animals. One month post-infusion, allogeneic CDCs reduced scar mass in both groups (continuous flow p=0.015 vs. baseline; stop-flow p=0.044). The effects on ejection fraction (p=0.08) and viable mass (p=0.88) were equivalent in the two groups. Conclusions: Nonocclusive continuous-flow delivery is equally efficient to stop-flow method as a means of cell delivery to the infarcted myocardium, at least for this particular cell type. The need for stop-flow delivery, while traditional, is therefore questionable.

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