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.
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.


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 x 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 x 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.
Erbs
Sandra
S
University of Leipzig, Heart Center, Department of Internal Medicine/Cardiology, Struempellstrasse 39, 04289 Leipzig, Germany. Sandra.Erbs@medizin.uni-leipzig.de
Linke
Axel
A
Schächinger
Volker
V
Assmus
Birgit
B
Thiele
Holger
H
Diederich
Klaus-Werner
KW
Hoffmann
Christina
C
Dimmeler
Stefanie
S
Tonn
Torsten
T
Hambrecht
Rainer
R
Zeiher
Andreas M
AM
Schuler
Gerhard
G
D016026:Bone Marrow Transplantation / Q000379:methods*; D003331:Coronary Vessels / Q000473:pathology / Q000502:physiology* / Q000601:surgery; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D017078:Laser-Doppler Flowmetry; D008297:Male; D008833:Microcirculation / Q000473:pathology / Q000502:physiology / Q000601:surgery; D008875:Middle Aged; D009203:Myocardial Infarction / Q000503:physiopathology / Q000601:surgery*; D013234:Stem Cells