Abstract 13641: Allogeneic Cardiosphere-Derived Cells Reduce Infarct Size and Attenuate No-Reflow when Administered in the Infarct-Related Artery after Reperfusion in Pigs with Acute Myocardial Infarction
Background: Intracoronary (IC) delivery of cardiosphere-derived cells (CDCs) has been demonstrated to be safe and effective in porcine and human ischemic cardiomyopathy. However, IC delivery of CDCs promptly after reperfusion has never been assessed in a clinically-relevant large animal model. We tested the safety and efficacy of CDCs as adjunctive therapy to reperfusion in a porcine model of acute myocardial infarction (AMI).
Methods and results: AMI was induced in 14 mini-pigs by balloon occlusion of the mid-LAD for 1.5h. Thirty minutes after reperfusion, pigs received, by prior random assignment, 12.5M allogeneic CDCs (n=4) or placebo solution (n=5), delivered by IC infusion in the mid-LAD, via an over-the-wire balloon catheter under stop-flow conditions. A sham group (n=5) had balloon placement in the infarct-related artery 30 min post-reperfusion but without inflations. Pigs were sacrificed 2 days post-MI to measure area at risk (AAR), infarct size (IS) and microvascular obstruction (MVO) utilizing TTC (2,3,5-triphenyl tetrazolium chloride) and thioflavin staining for IS and MVO, respectively.
Results: No deaths were observed in any of the groups after reperfusion. IS/AAR was smaller in the CDC group (59.7%, P<0.01 vs sham and placebo) compared with sham (79.2%) or placebo (77.2%) groups. In addition, the area of no reflow (MVO/AAR) was smaller in the CDC group (52.9%, P<0.01, P=0.014 vs sham and placebo, respectively) than in sham (71.8%) or placebo (65.7%) groups. Serum troponin I continued to rise post-intervention in sham and placebo groups (+203% and +230% respectively at 24 hours, relative to pre-intervention), but fell by 52% in the CDC group (P<0.05), consistent with the histologically-demonstrated reduction in myocardial injury. Left ventriculography demonstrated progressive left ventricular dilatation in placebo and sham groups at 2 day post-MI, but not in CDC treated-pigs.
Conclusions: IC delivery of CDCs immediately after reperfusion is safe and feasible. The acute infusion of CDCs is effective in reducing infarct size, preventing microvascular obstruction and attenuating adverse acute remodeling. The present results give good reason to develop allogeneic CDCs as adjunctive therapy for AMI in humans.
- © 2012 by American Heart Association, Inc.