Llano Raul, Epstein Samuel, Zhou Rong, Zhang Hualei, Hamamdzic Damir, Keane Martin G, Freyman Toby, Wilensky Robert L
Cardiovascular Division, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Catheter Cardiovasc Interv. 2009 Feb 1;73(2):251-7. doi: 10.1002/ccd.21781.
Evaluate the effects of pressure and duration of intracoronary (IC) infusion of mesenchymal stem cells (MSCs) on delivery efficiency and safety after myocardial infarction (MI).
Standard IC delivery of MSCs can lead to intravascular plugging and reduced coronary blood flow. The optimal delivery pressure and duration is unknown.
Immediately after MI pigs were randomized to 1 of 3 delivery protocols of 5 x 10(7) iron-fluorescent microspheres labeled MSCs, control received 2 ml infusions at 1 ml/min (five times), very high flow rate (VHFR) a single 10 ml infusion at 60 ml/min and the high flow rate (HFR) group a single 10 ml infusion at 20 ml/min. TIMI grade flow was assessed throughout the procedure and at sacrifice (day 14). MSCs distribution was analyzed in isolated hearts by 4.7T MRI. Delivery efficiency was quantified via fluorescent microsphere recovery using a magnetic separation technique and by light microscopy.
TIMI grade flow did not change following MI (all groups TIMI 3). However, following MSCs delivery only 18% (2/11) of control animals had TIMI 3 blood flow vs. 56% (5/9) in VHFR and 67% (4/6) in HFR (P = 0.03). As a consequence, 63% of control animals died within 24 hr, 33% in VHFR and none in HFR (P = 0.02). MSCs delivery in the infarct tissue did not differ between the groups (P = 0.06).
A single MSCs infusion at 20 ml/min resulted in improved coronary blood flow and decreased mortality, without sacrificing delivery efficiency.
评估心肌梗死（MI）后冠状动脉内（IC）输注间充质干细胞（MSCs）的压力和持续时间对递送效率及安全性的影响。
MSCs的标准IC递送可导致血管内堵塞并减少冠状动脉血流。最佳递送压力和持续时间尚不清楚。
MI后立即将猪随机分为3种递送方案之一，即5×10⁷个铁荧光微球标记的MSCs，对照组以1 ml/min的速度输注2 ml（共5次），极高流速（VHFR）组以60 ml/min的速度单次输注10 ml，高流速（HFR）组以20 ml/min的速度单次输注10 ml。在整个操作过程中及处死时（第14天）评估心肌梗死溶栓试验（TIMI）血流分级。通过4.7T磁共振成像（MRI）分析分离心脏中的MSCs分布。使用磁分离技术并通过光学显微镜，通过荧光微球回收对递送效率进行定量。
MI后TIMI血流分级未改变（所有组TIMI 3级）。然而，在输注MSCs后，对照组动物中只有18%（2/11）具有TIMI 3级血流，而VHFR组为56%（5/9），HFR组为67%（4/6）（P = 0.03）。因此，63%的对照组动物在24小时内死亡，VHFR组为33%，HFR组无死亡（P = 0.02）。各组间梗死组织中的MSCs递送无差异（P = 0.06）。
以20 ml/min的速度单次输注MSCs可改善冠状动脉血流并降低死亡率，且不影响递送效率。
