Erbs Sandra, Linke Axel, Schächinger Volker, Assmus Birgit, Thiele Holger, Diederich Klaus-Werner, Hoffmann Christina, Dimmeler Stefanie, Tonn Torsten, Hambrecht Rainer, Zeiher Andreas M, Schuler Gerhard
University of Leipzig, Heart Center, Department of Internal Medicine/Cardiology, Struempellstrasse 39, 04289 Leipzig, Germany.
Circulation. 2007 Jul 24;116(4):366-74. doi: 10.1161/CIRCULATIONAHA.106.671545. Epub 2007 Jul 9.
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.
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).
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.
急性心肌梗死中富集祖细胞再灌注与梗死重塑的随机、双盲、安慰剂对照试验(REPAIR-AMI)的多普勒子研究旨在调查冠状动脉内输注骨髓来源的祖细胞(BMCs)对再灌注急性心肌梗死患者冠状动脉血流调节的影响。
共纳入58例患者(BMC组,n = 30;安慰剂组,n = 28),在研究治疗时(急性心肌梗死后4.2±0.1天)及4个月随访时通过冠状动脉内多普勒评估梗死相关动脉和参照血管的冠状动脉血流储备(CFR)。两组梗死相关动脉的初始CFR均低于参照血管(BMC组:2.0±0.1对2.9±0.2,P<0.05;安慰剂组:1.9±0.1对2.8±0.2;P<0.05)。在4个月随访时,安慰剂组梗死相关动脉的CFR略有改善(+0.88±0.18;与初始值相比P<0.001),但在接受BMC治疗的患者中显著增加90%(+1.80±0.25;与安慰剂组相比P = 0.005),导致CFR恢复正常(3.8±0.2;与初始值及4个月时的安慰剂组相比P<0.001)。在梗死血管中,安慰剂组腺苷诱导的最小血管阻力指数略有下降(从1.77±0.12降至1.52±0.15 mmHg·s/cm;P<0.05),而BMC组显著下降-29±6%(从1.86±0.19降至1.20±0.12 mmHg·s/cm;与初始值及4个月时的安慰剂组相比P<0.05)。
急性心肌梗死后冠状动脉内BMC治疗可恢复梗死相关动脉的微血管功能,这与最大血管传导能力的显著改善相关。这些数据提供了祖细胞移植促进血管修复的临床概念验证。