George Jon C, Goldberg Jonathan, Joseph Matthew, Abdulhameed Nasreen, Crist Joshua, Das Hiranmoy, Pompili Vincent J
Cardiovascular Research Institute, Case Western Reserve University, Cleveland, OH, USA.
J Interv Cardiol. 2008 Oct;21(5):424-31. doi: 10.1111/j.1540-8183.2008.00390.x.
Clinical trials using intracoronary (IC) delivery of cells have addressed efficacy but the optimal delivery technique is unknown. Our study aimed to determine whether transvenous intramyocardial (TVIM) approach was advantageous for cellular retention in AMI.
Domestic pigs (n = 4) underwent catheterization with coronary angiography and ventriculography prior to infarction and pre- and post-cells. Pigs underwent 90-minute balloon occlusion of the left anterior descending artery (LAD). After one week they were prepared for IC (n = 2) or TVIM (n = 2) delivery of bone marrow mononuclear cells (MNC) labeled with GFP. IC infusion used an over-the-wire catheter to engage the LAD and balloon inflation to prevent retrograde flow. Venography via the coronary sinus was used for TVIM delivery. The anterior interventricular vein was engaged with a guidewire allowing use of the TransAccess catheter that is outfitted with an ultrasound tip for visualization. Animals were sacrificed one hour after delivery and tissue was analyzed.
Procedures were performed without complication and monitoring was uneventful. 1 x 10(8) MNC were isolated from each bone marrow (BM) preparation and 1 x 10(7) MNC delivered. Ventriculography at one week revealed wall motion abnormalities consistent with an anterior AMI. TVIM and IC delivery revealed mean 452 cells per section and 235 cells per section on average, respectively, in the infarct zone (P = 0.01).
We have demonstrated that TVIM approach for cell delivery is feasible and safe. Moreover, this approach may provide an advantage over IC infusion in retention of the cellular product; however, larger studies will be necessary.
使用冠状动脉内(IC)细胞递送的临床试验已探讨了疗效,但最佳递送技术尚不清楚。我们的研究旨在确定经静脉心肌内(TVIM)方法是否有利于急性心肌梗死(AMI)中的细胞留存。
4头家猪在梗死前以及细胞注射前后接受冠状动脉造影和心室造影导管插入术。家猪接受左前降支动脉(LAD)90分钟的球囊闭塞。一周后,它们准备接受用绿色荧光蛋白(GFP)标记的骨髓单个核细胞(MNC)的IC(n = 2)或TVIM(n = 2)递送。IC输注使用导丝导管进入LAD并进行球囊扩张以防止逆行血流。通过冠状窦进行静脉造影用于TVIM递送。使用导丝进入前室间静脉,允许使用配备超声探头以进行可视化的TransAccess导管。在递送后1小时处死动物并分析组织。
手术过程无并发症,监测情况良好。从每个骨髓(BM)制剂中分离出1×10⁸个MNC,并递送1×10⁷个MNC。一周后的心室造影显示与前壁AMI一致的壁运动异常。TVIM和IC递送在梗死区域平均每切片分别显示452个细胞和235个细胞(P = 0.01)。
我们已证明TVIM细胞递送方法是可行且安全的。此外,这种方法在细胞产物留存方面可能比IC输注具有优势;然而,需要进行更大规模的研究。