直接心肌内自体骨髓移植恢复局部而非整体收缩功能：一项随机对照临床试验的结果

Recovery of regional but not global contractile function by the direct intramyocardial autologous bone marrow transplantation: results from a randomized controlled clinical trial.

作者信息

Hendrikx Marc, Hensen Karen, Clijsters Christel, Jongen Hanne, Koninckx Remco, Bijnens Eric, Ingels Michel, Jacobs Axel, Geukens Robert, Dendale Paul, Vijgen Johan, Dilling Dagmara, Steels Paul, Mees Urbain, Rummens Jean-Luc

机构信息

Department of Cardiothoracic Surgery, Virga Jesse hospital, Stadsomvaart 11, B-3500 Hasselt, Belgium.

出版信息

Circulation. 2006 Jul 4;114(1 Suppl):I101-7. doi: 10.1161/CIRCULATIONAHA.105.000505.

DOI:10.1161/CIRCULATIONAHA.105.000505

PMID:16820557

Abstract

BACKGROUND

Recent trials have shown that intracoronary infusion of bone marrow cells (BMCs) improves functional recovery after acute myocardial infarction. However, whether this treatment is effective in heart failure as a consequence of remodeling after organized infarcts remains unclear. In this randomized trial, we assessed the hypothesis that direct intramyocardial injection of autologous mononuclear bone marrow cells during coronary artery bypass graft (CABG) could improve global and regional left ventricular ejection fraction (LVEF) at 4-month follow-up.

METHODS AND RESULTS

Twenty patients (age 64.8+/-8.7; 17 male, 3 female) with a postinfarction nonviable scar, as assessed by thallium (Tl) scintigraphy and cardiac magnetic resonance imaging (MRI), scheduled for elective CABG, were included. They were randomized to a control group (n =10, CABG only) or a BMC group (CABG and injection of 60.10(6)+/-31.10(6) BMC). Primary end points were global LVEF change and wall thickening changes in the infarct area from baseline to 4-month follow-up, as measured by MRI. Changes in metabolic activity were measured by Tl scintigraphy and expressed as a score with a range from 0 to 4, corresponding to percent of maximal myocardial Tl uptake (4 indicates <50%, nonviable scar; 3, 50% to 60%; 2, 60% to 70%; 1, 70% to 80%; 0>80%). Global LVEF at baseline was 39.5+/-5.5% in controls and 42.9+/-10.3% in the BMC group (P=0.38). At 4 months, LVEF had increased to 43.1+/-10.9% in the control group and to 48.9+/-9.5% in the BMC group (P=0.23). Systolic thickening had improved from -0.6+/-1.3 mm at baseline to 1.8+/-2.6 mm at 4 months in the cell-implanted scars, whereas nontreated scars remained largely akinetic (-0.5+/-2.0 mm at baseline compared with 0.4+/-1.7 mm at 4 months, P=0.007 control versus BMC-treated group at 4 months). Defect score decreased from 4 to 3.3+/-0.9 in the BMC group and to 3.7+/-0.4 in the control group (P=0.18).

CONCLUSIONS

At 4 months, there was no significant difference in global LVEF between both groups, but a recovery of regional contractile function in previously nonviable scar was observed in the BMC group.

摘要

背景

近期试验表明，冠状动脉内注入骨髓细胞（BMCs）可改善急性心肌梗死后的功能恢复。然而，对于这种治疗方法在梗死灶机化后重塑导致的心力衰竭中是否有效仍不清楚。在这项随机试验中，我们评估了以下假设：在冠状动脉旁路移植术（CABG）期间直接心肌内注射自体单核骨髓细胞可在4个月随访时改善整体和局部左心室射血分数（LVEF）。

方法与结果

纳入20例患者（年龄64.8±8.7岁；17例男性，3例女性），经铊（Tl）闪烁显像和心脏磁共振成像（MRI）评估为梗死灶心肌无活性，计划行择期CABG。他们被随机分为对照组（n = 10，仅行CABG）或BMC组（CABG并注射60×10⁶±31×10⁶个BMC）。主要终点为通过MRI测量的从基线到4个月随访时整体LVEF变化以及梗死区域的室壁增厚变化。通过Tl闪烁显像测量代谢活性变化，并表示为0至4分的评分，对应最大心肌Tl摄取百分比（4分表示＜50%，无活性瘢痕；3分，50%至60%；2分，60%至70%；1分，70%至80%；0分＞80%）。对照组基线时的整体LVEF为39.5±5.5%，BMC组为42.9±10.3%（P = 0.38）。4个月时，对照组LVEF增至43.1±10.9%，BMC组增至48.9±9.5%（P = 0.23）。细胞植入瘢痕处的收缩期增厚从基线时的-0.6±1.3 mm改善至4个月时的1.8±2.6 mm，而未治疗的瘢痕在很大程度上仍无运动（基线时为-0.5±2.0 mm，4个月时为0.4±1.7 mm，4个月时对照组与BMC治疗组比较P = 0.007）。BMC组的缺损评分从4分降至3.3±0.9分，对照组降至3.7±0.4分（P = 0.18）。