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急性心肌梗死后自体骨髓来源祖细胞移植促进心肌再生

Autologous bone marrow-derived progenitor cell transplantation for myocardial regeneration after acute infarction.

作者信息

Obradović Slobodan, Rusović Sinisa, Balint Bela, Ristić-Andelkov Andelka, Romanović Radoslav, Baskot Branislav, Vojvodić Danilo, Gligić Branko

机构信息

Military Medical Academy, Clinic of Emergency Medicine, Belgrade, Serbia & Montenegro.

出版信息

Vojnosanit Pregl. 2004 Sep-Oct;61(5):519-29. doi: 10.2298/vsp0405519o.

Abstract

BACKGROUND

Experimental and first clinical studies suggest that the transplantation of bone marrow derived, or circulating blood progenitor cells, may beneficially affect postinfarction remodelling processes after acute myocardial infarction.

AIM

This pilot trial reports investigation of safety and feasibility of autologous bone marrow-derived progenitor cell therapy for faster regeneration of the myocardium after infarction.

METHODS AND RESULTS

Four male patients (age range 47-68 years) with the first extensive anterior, ST elevation, acute myocardial infarction (AMI), were treated by primary angioplasty. Bone marrow mononuclear cells were administered by intracoronary infusion 3-5 days after the infarction. Bone marrow was harvested by multiple aspirations from posterior cristae iliacae under general anesthesia, and under aseptic conditions. After that, cells were filtered through stainless steel mesh, centrifuged and resuspended in serum-free culture medium, and 3 hours later infused through the catheter into the infarct-related artery in 8 equal boluses of 20 ml. Myocardial viability in the infarcted area was confirmed by dobutamine stress echocardiography testing and single-photon emission computed tomography (SPECT) 10-14 days after infarction. One patient had early stent thrombosis immediately before cell transplantation, and was treated successfully with second angioplasty. Single average ECG revealed one positive finding at discharge, and 24-hour Holter ECG showed only isolated ventricular ectopic beats during the follow-up period. Early findings in two patients showed significant improvement of left ventricular systolic function 3 months after the infarction. There were no major cardiac events after the transplantation during further follow-up period (30-120 days after infarction). Control SPECT for the detection of ischemia showed significant improvement in myocardial perfusion in two patients 4 months after the infarction. Echocardiographic assessment in these two patients also showed significant improvement of systolic function three months after the infarction.

CONCLUSION

Preliminary results of the study showed that the transplantation of bone marrow-derived progenitor cells into the infarcted area was safe, and feasible, and might improve myocardial function. Further follow-up will show if this treatment is effective in preventing negative remodeling of the left ventricle and reveal potential late adverse events (arrhythmogenicity and propensity for restenosis).

摘要

背景

实验研究和首批临床研究表明,移植骨髓来源的或循环血液祖细胞可能对急性心肌梗死后的梗死重塑过程产生有益影响。

目的

这项试点试验报告了自体骨髓来源的祖细胞疗法促进梗死后心肌更快再生的安全性和可行性研究。

方法与结果

4名男性患者(年龄范围47 - 68岁),首次发生广泛前壁ST段抬高型急性心肌梗死(AMI),接受了直接经皮冠状动脉介入治疗。在梗死3 - 5天后通过冠状动脉内输注给予骨髓单个核细胞。在全身麻醉和无菌条件下,通过多次穿刺从髂后嵴采集骨髓。之后,细胞通过不锈钢网过滤、离心并重悬于无血清培养基中,3小时后通过导管以8次等量20毫升推注的方式注入梗死相关动脉。在梗死后10 - 14天通过多巴酚丁胺负荷超声心动图检查和单光子发射计算机断层扫描(SPECT)确认梗死区域的心肌活力。1例患者在细胞移植前即刻发生早期支架血栓形成,经再次经皮冠状动脉介入治疗成功。单次平均心电图显示出院时有1项阳性发现,24小时动态心电图显示随访期间仅出现孤立性室性早搏。2例患者的早期结果显示梗死后3个月左心室收缩功能有显著改善。在进一步随访期间(梗死后30 - 120天)移植后未发生重大心脏事件。用于检测缺血的对照SPECT显示,2例患者在梗死后4个月心肌灌注有显著改善。这2例患者的超声心动图评估也显示梗死后3个月收缩功能有显著改善。

结论

该研究的初步结果表明,将骨髓来源的祖细胞移植到梗死区域是安全可行的,并且可能改善心肌功能。进一步的随访将表明这种治疗是否能有效预防左心室的不良重塑,并揭示潜在的晚期不良事件(致心律失常性和再狭窄倾向)。

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