Department of Cardiology, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria.
Stem Cell Rev Rep. 2011 Sep;7(3):616-23. doi: 10.1007/s12015-010-9213-7.
The aim of the present study was to investigate the changes in absolute myocardial blood flow (AMF) after intracoronary injections of mesenchymal SC (MSC) and compared to controls in closed-chest reperfused acute myocardial infarction (AMI) in pigs. Male MSCs, transiently transfected with Luciferase (Luc-MSC) were delivered (9.7 ± 1.2 x 10(6)) intracoronary in the open infarct-related artery one-week post-AMI in female pigs (group MSC), while saline was injected with the same injection rate in controls (group C). The AMF was measured immediately after, and 3, 12 and 24 h post-intracoronary Luc-MSC or saline injections. In vitro bioluminescence images and quantitative real-time TaqMan PCR measurements were performed to quantify the sex-mismatched MSCs. No difference between the groups was observed regarding the weight, heart rate, blood pressure and global ejection fraction 1-week post-AMI. The baseline AMF were similar in the groups (61.3 ± 15. vs 61.1 ± 12.0 ml/min). AMF was decreased significantly immediately after intracoronary MSC delivery (42.0 ± 12.4 vs 57.7 ± 15.7 ml/min p = 0.013), and remained low at 3 h (40.9 ± 13.4 vs 55.8 ± 4.9 ml/min, p = 0.004), 12 h (43.0 ± 3.7 vs 57.8 ± 5.4 ml/min, p = 0.001) with incomplete recovery at 24 h (47.2 ± 5.5 vs 62.1 ± 14.1 ml/min, p = 0.038) as compared to controls, respectively. In vitro bioluminescence displayed transfected Luc-MSCs along the proximal and mid part of the LAD, with limited number (295 ± 101 sry copied/million cardiac cells) of Y-chromosome-MSCs in the infarcted area. Intracoronary injection of SCs results in immediate decrease of AMF, with delayed recovery. The delivery of the SC into the injured myocardium might be hindered by the altered coronary pressure and flow conditions.
本研究旨在探讨经冠状动脉注射间充质干细胞(MSC)后绝对心肌血流(AMF)的变化,并与猪急性心肌梗死(AMI)再灌注后封闭胸廓的对照进行比较。在雌性猪 AMI 后一周,将瞬时转染 Luciferase(Luc-MSC)的雄性 MSC(MSC 组)以 9.7 ± 1.2 x 10(6) 的速度经冠状动脉注入开放梗死相关动脉,而在对照组(C 组)中以相同的注射速度注射盐水。在 Luc-MSC 或盐水注射后立即、3、12 和 24 小时测量 AMF。进行体外生物发光图像和定量实时 TaqMan PCR 测量以定量测定性别错配的 MSC。AMI 后一周,两组之间的体重、心率、血压和整体射血分数无差异。两组的基线 AMF 相似(61.3±15. vs 61.1±12.0 ml/min)。经冠状动脉 MSC 给药后 AMF 显著降低(42.0±12.4 vs 57.7±15.7 ml/min,p=0.013),3 小时时仍较低(40.9±13.4 vs 55.8±4.9 ml/min,p=0.004),12 小时时(43.0±3.7 vs 57.8±5.4 ml/min,p=0.001),24 小时时不完全恢复(47.2±5.5 vs 62.1±14.1 ml/min,p=0.038)与对照组相比。体外生物发光显示转染的 Luc-MSCs 沿 LAD 的近段和中段,梗死区仅有少量(295±101 sry 拷贝/百万心脏细胞)Y 染色体-MSCs。SC 经冠状动脉注射后立即降低 AMF,延迟恢复。SC 输送到受损心肌可能会受到改变的冠状动脉压力和血流条件的阻碍。