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. 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 center dot 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 center dot 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.