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

Abstract

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.

Impact of Timing on Efficacy and Safetyof Intracoronary Autologous Bone Marrow Stem Cells Transplantation in Acute Myocardial Infarction: A Pooled Subgroup Analysis of Randomized Controlled Trials

“…The potential mechanism is not well documented in previous studies. Recent studies suggested that BMSC infused into the coronary circulation at 4 to 7 days post-AMI reconstituted the damaged endothelium and promoted neovascularization, 22 which increased coronary flow reserve in the infarct-related artery. The improved perfusion capacity might stimulate the endothelium to release nitric oxide, which exerted antiatherosclerotic functions and might counteract the process of restenosis development and atherosclerotic disease progression.…”

State-of-the-Art Methods for Evaluation of Angiogenesis and Tissue Vascularization

“…Angiography has also been used to estimate microvascular function and microvascular growth. 176,177 A limitation of this approach is that only measurements of vasodilator reserve are obtained, not measurements of volume flow. Vasodilator reserve can be affected by downstream angiogenesis and influenced by the basal tone of the vasculature.…”

A Randomized Comparative Study on the Efficacy of Intracoronary Infusion of Autologous Bone Marrow Mononuclear Cells and Mesenchymal Stem Cells in Patients With Dilated Cardiomyopathy

“…6,25) Based on this evidence, larger trials have confirmed that intracoronary injection of autologous BMC is safe and potentially effective. 26) The beneficial effects of cell therapy in the setting of ischemic heart disease are not fully understood, and proposed mechanisms of action have included cardiomyocyte regeneration, 3,5,22) angiogenesis, [3][4][5]16,21,22,25) and inhibition of myocardial apoptosis and ventricular remodeling through paracrine factors of the infused cells. 3,14,21) The capacity of BMC to regenerate myocytes has been a matter of intense debate to date.…”