Published Online
on July 9, 2007

A more recent version of this article appeared on July 24, 2007

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Submitted on November 3, 2006
Accepted on May 3, 2007

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, and 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.

^* To whom correspondence should be addressed. E-mail: Sandra.Erbs{at}medizin.uni-leipzig.de.

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.

Key words: angiogenesis • cells • microcirculation • myocardial infarction

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