经冠状动脉自体骨髓单个核细胞移植治疗急性心肌梗死的安全性观察

Observation on the safety: clinical trail on intracoronary autologus bone marrow mononuclear cells transplantation for acute myocardiol infarction

目的采用随机对照研究方法观察经冠状动脉自体骨髓单个核细胞(BM-MNCs)移植治疗急性心肌梗死(AMI)的安全性。方法入选184例AMI患者,分为细胞移植组92例和对照组92例,两组患者在药物治疗基础上,分别在介入治疗同时,经微导管于梗死相关动脉内支架远端注入自体BM-MNCs悬液或等量的肝素生理盐水(对照组)。记录骨髓收集及分离过程中可能出现的迷走反射(如面色苍白、晕厥、恶心、低血压甚至休克)、心绞痛发作、心力衰竭加重等,细胞悬液输注中可能出现的心律失常(窦性心动过缓、窦性停搏或三度房室传导阻滞、心室颤动)、低血压、栓塞等不良反应。监测术后1周内体温、心率、血压、心肌酶谱变化,并根据预先设定的时间点行24小时动态心电图、血常规、肝肾功能、血糖、血脂、血尿酸、心肌酶谱和高敏C反应蛋白(hs-CRP)检测,定期复查冠状动脉造影和经胸超声心动图。计划随访2年,记录主要心脏事件发生率、支架内再狭窄以及肿瘤等发生情况。结果在骨髓收集和分离过程中患者未出现心绞痛发作、心力衰竭加重等并发症,迷走反射相关不良反应均为一过性。两组患者平均随访(14．5±8．1)个月。与对照组相比,移植组围手术期及随访期间不良事件发生率差异无统计学意义:围手术期(≤1周)4．3％比5．7％(P>0．05);术后3个月为3．5％比2．4％(P>0．05);术后6个月至30个月为11．7％比14．3％(P>0．05)。未发现与移植相关的恶性心律失常、感染、心肌缺血加重、支架内再狭窄增加等。随访期间未发生死亡、新发肿瘤、栓塞等事件。同时,与对照组相比,BM-MNCs移植可以在介入治疗的基础上进一步提高左室射血分数。结论经冠状动脉自体BM-MNCs移植治疗AMI安全可行,且能改善心功能。

Objective To investigate the safety of autologous bone marrow mononuclear cell （ BM- MNCs） transplantation by intracoronary infusion in patients with acute myocardial infarction （AMI）. Methods One hundred and eighty-four patients with AMI treated with percutaneous coronary intervention （PCI） were randomized in a 1 ： 1 way to either intracoronary transplantation of autologous BM-MNCs（ n = 92 ） right after PCI or to sodium chloride concluding heparin （ controlled, n = 92） via a micro infusion catheter. In the process of the intracoronary infusion of BM-MNCs, the complications should be recorded, which were aberration reflect （including of pale, syncope, nausea, hypotenstion and shock）, deterioration of angina or heart failure, arrhythmias （ including of bradycardia, sinus arrest or atrial ventricular block or ventricular fibrillation）, embolism etc. Body temperature, blood pressure and heart rates should be monitored during the first week after transplantation. Holter, coronary angiography and ultrasonic cardiography were performed at the designed time points. Main heart accidents, restenosis and tumor were recorded during 2-years follow up. Results During the period of bone marrow puncture and intracoronary infusion of BM-MNCs, few patients occured pale, dizziness, bradycardia and hypotension, which were transient and due to vagus reflect. No stem cell-related arrhythmias, deterioration of angina were noted. In BM-MNCs grop one patient developed in-stent reocclusion in one week after transplantation, five developed in-stent restenosis during further follow-up 30 months, which were similar with control group. There were no deaths, major adverse cardiac events, tumor and other late adverse events during follow-up period in both groups. Conclusion Intracoronary transplantation of autologous BM-MNCs in the acute phase after AMI is feasible and seems safe in the 30 months of follow-up.