Author + information
- Hideaki Kanazawa,
- Konstantinos Malliaras,
- Kristine Yee,
- James Dawkins,
- Eleni Tseliou,
- Linda Marbán,
- Rajendra Makkar and
- Eduardo Marban
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).
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 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.
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 (81.0%) or placebo (80.3%) groups. In addition, the area of no reflow (MVO/AAR) was smaller in the CDC group (52.9%, P=0.027, P=0.002 vs sham and placebo, respectively) than in sham (72.8%) or placebo (70.3%) groups. The serum Troponin–I level 24 hours after cell infusion of CDC treated pigs was lower than that in the pigs infused with placebo (P=0.034), or the sham group (P<0.01), consistent with the histologically–demonstrated reduction in myocardial injury. Left ventriculography demonstrated progressive left ventricular dilatation in placebo and sham groups 2 days post–MI, but not in CDC treated–pigs.
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.
Poster Sessions, Expo North
Sunday, March 10, 2013, 3:45 p.m.–4:30 p.m.
Session Title: Cell Therapy and Angiogenesis
Abstract Category: 42. TCT@ACC–i2: Cell Therapy & Angiogenesis
Presentation Number: 2110–230
- 2013 American College of Cardiology Foundation