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(Circulation. 2007;116:366-374.)
© 2007 American Heart Association, Inc.

Coronary Heart Disease

Restoration of Microvascular Function in the Infarct-Related Artery by Intracoronary Transplantation of Bone Marrow Progenitor Cells in Patients With Acute Myocardial Infarction

The Doppler Substudy of the Reinfusion of Enriched Progenitor Cells and Infarct Remodeling in Acute Myocardial Infarction (REPAIR-AMI) Trial

Sandra Erbs, MD; Axel Linke, MD; Volker Schächinger, MD; Birgit Assmus, MD; Holger Thiele, MD; Klaus-Werner Diederich, MD; Christina Hoffmann, MD; Stefanie Dimmeler, PhD; Torsten Tonn, MD; Rainer Hambrecht, MD; Andreas M. Zeiher, MD; Gerhard Schuler, MD

From the University of Leipzig, Heart Center, Department of Cardiology, Leipzig (S.E., A.L., H.T., K.-W.D., R.H., G.S.); J.W. Goethe University Frankfurt, Departments of Cardiology (V.S., B.A., S.D., A.M.Z.) and Transfusion Medicine (T.T.), Frankfurt; and Heart and Diabetes Center NRW, Ruhr University of Bochum, Bad Oeynhausen (C.H.), Germany.

Correspondence to Sandra Erbs, MD, University of Leipzig, Heart Center, Department of Internal Medicine/Cardiology, Struempellstrasse 39, 04289 Leipzig, Germany. E-mail Sandra.Erbs{at}medizin.uni-leipzig.de

Received November 3, 2006; accepted May 3, 2007.

Background— The Doppler Substudy of the randomized, double-blind, placebo-controlled Reinfusion of Enriched Progenitor Cells and Infarct Remodeling in Acute Myocardial Infarction (REPAIR-AMI) trial aimed to investigate the effects of intracoronary infusion of bone marrow–derived progenitor cells (BMCs) on coronary blood flow regulation in patients with reperfused acute myocardial infarction.

Methods and Results— In a total of 58 patients (BMC group, n=30; placebo group, n=28), coronary flow reserve (CFR) in the infarct artery and a reference vessel was assessed by intracoronary Doppler at the time of study therapy (4.2±0.1 days after acute myocardial infarction) and at the 4-month follow-up. Initial CFR was reduced in the infarct artery compared with the reference vessel in both groups (BMC: 2.0±0.1 versus 2.9±0.2, P<0.05; placebo: 1.9±0.1 versus 2.8±0.2; P<0.05). At the 4-month follow-up, CFR in the infarct artery had slightly improved in the placebo group (+0.88±0.18; P<0.001 versus initial) but was markedly increased by 90% (+1.80±0.25; P=0.005 versus placebo) in BMC-treated patients, resulting in a normalization of CFR (3.8±0.2; P<0.001 versus initial and placebo at 4 months). In the infarct vessel, adenosine-induced minimal vascular resistance index declined slightly in the placebo group (from 1.77±0.12 to 1.52±0.15 mm Hg · s/cm; P<0.05) but considerably decreased by –29±6% in the BMC group (from 1.86±0.19 to 1.20±0.12 mm Hg · s/cm; P<0.05 versus initial and placebo at 4 months).

Conclusions— Intracoronary BMC therapy after acute myocardial infarction restores microvascular function of the infarct-related artery, which is associated with a significant improvement in maximal vascular conductance capacity. These data provide clinical proof of concept that progenitor cell transplantation promotes vascular repair.

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