Koch Karl-Christian, Schaefer Wolfgang M, Liehn Elisa A, Rammos Christos, Mueller Dominik, Schroeder Joerg, Dimassi Tarek, Stopinski Thaddaeus, Weber Christian
Department of Cardiology, RWTH Aachen University, Pauwelstrasse 30, 52074 Aachen, Germany.
Basic Res Cardiol. 2006 Jan;101(1):69-77. doi: 10.1007/s00395-005-0570-3.
Myocardial regeneration after myocardial infarction can occur via stem cell recruitment. Stromal cell-derived factor 1alpha (SDF-1alpha) has been shown to be critical for stem cell homing to injured tissue.
Myocardial infarction was induced in pigs via microembolization of the distal left anterior descending artery. Two weeks after myocardial infarction animals underwent catheter-based transendocardial injection of SDF-1alpha into the periinfarct myocardium (18 injections, 5 ìg per injection) (n = 12) or sham-intervention (n = 8). Tc99m sestamibi single-photon emission computed tomography (SPECT) and electromechanical mapping (EMM) of the left ventricle were performed two and seven weeks after myocardial infarction.
Infarct size by tetrazolium staining was similar in both groups (8.9 +/-1.2% of left ventricle vs. 8.9 +/- 2.6%). Vessel density in the periinfarct area was significantly higher in SDF-1alpha treated animals than in controls (349 +/- 17/mm2 vs. 276 +/- 21/mm2, p < 0.05). Myocardial perfusion (SPECT) did not change in either group. Ejection fraction and stroke volume (EMM) decreased in SDF-1alpha animals and increased in controls (difference between groups p = 0.05 for ejection fraction and p < 0.05 for stroke volume). Linear local shortening (EMM) did not change in controls (11.4 +/- 1.3% to 11.5 +/- 0.5%) but decreased significantly in SDF-1alpha treated animals (12.1 +/- 0.9% to 8.4 +/- 0.9%, p < 0.05, p < 0.05 for difference between groups). SDF-1 delivery was associated with a substantial loss of collagen in the periinfarct area (32+/-5% vs. 61+/-6% in control animals, p < 0.005).
A strategy to augment stem cell homing by catheter-based transendocardial delivery of SDF-1alpha in experimental myocardial infarction increases periinfarct vessel density, fails to improve myocardial perfusion, is associated with loss of collagen in the periinfarct area and impairs left ventricular function.
心肌梗死后的心肌再生可通过干细胞募集实现。基质细胞衍生因子1α（SDF-1α）已被证明对干细胞归巢至损伤组织至关重要。
通过微栓塞左前降支远端诱导猪发生心肌梗死。心肌梗死后两周，对动物进行基于导管的经心内膜向梗死周边心肌注射SDF-1α（18次注射，每次注射5μg）（n = 12）或假干预（n = 8）。在心肌梗死后两周和七周进行左心室的Tc99m 甲氧基异丁基异腈单光子发射计算机断层扫描（SPECT）和机电映射（EMM）。
两组间通过四氮唑染色测定的梗死面积相似（左心室的8.9±1.2% 对8.9±2.6%）。SDF-1α治疗组动物梗死周边区域的血管密度显著高于对照组（349±17/mm² 对276±21/mm²，p < 0.05）。两组的心肌灌注（SPECT）均未改变。SDF-1α组动物的射血分数和每搏输出量（EMM）降低，而对照组增加（两组间射血分数的差异p = 0.05，每搏输出量的差异p < 0.05）。对照组的线性局部缩短（EMM）未改变（从11.4±1.3%至11.5±0.5%），但在SDF-1α治疗组动物中显著降低（从12.1±0.9%至8.4±0.9%，p < 0.05，两组间差异p < 0.05）。SDF-1的递送与梗死周边区域大量胶原蛋白丢失相关（32±5% 对对照组动物的61±6%，p < 0.005）。
在实验性心肌梗死中，通过基于导管的经心内膜递送SDF-1α来增强干细胞归巢的策略可增加梗死周边血管密度，但未能改善心肌灌注，与梗死周边区域胶原蛋白丢失相关且损害左心室功能。
