Effect of catheter-based transendocardial delivery of stromal cell-derived factor 1α on left ventricular function and perfusion in a porcine model of myocardial infarction
Effect of catheter-based transendocardial delivery of stromal cell-derived factor 1α on left ventricular function and perfusion in a porcine model of myocardial infarction
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DOI：
10.1007/s00395-005-0570-3
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发表时间：
2006-01-01
影响因子：
9.5
通讯作者：
Weber, C
中科院分区：
文献类型：
--
作者：
Koch, KC;Schaefer, WM;Weber, C
心肌梗死后心肌再生可通过干细胞募集实现。基质细胞衍生因子1 α (SDF-1 α)已被证明是干细胞归巢到损伤组织的关键。方法采用左前降支远端微栓塞法诱导猪心肌梗死。心肌梗死2周后，动物在梗死周围心肌内经导管注射SDF-1 α(18针，每针5 μ g) （n = 12）或假干预（n = 8）。心肌梗死后2周和7周分别进行左心室单光子发射计算机断层扫描（SPECT）和机电成像（EMM）。结果四氮唑染色梗死面积两组相似（左心室8.9 +/- 1.2% vs 8.9 +/- 2.6%）。SDF-1 α处理动物梗死周围血管密度显著高于对照组(349 +/- 17/mm（2) vs. 276 +/- 21/mm(2), p < 0.05）。两组心肌灌注（SPECT）无明显变化。SDF-1 α动物的射血分数和脑卒中容积（EMM）下降，对照组升高（射血分数组间差异p = 0.05，脑卒中容积组间差异p < 0.05）。对照组线性局部缩短（EMM）无变化（11.4 +/- 1.3% ~ 11.5 +/- 0.5%），但SDF-1 α处理组显著降低（12.1 +/- 0.9% ~ 8.4 +/- 0.9%,p < 0.05，组间差异p < 0.05）。SDF-1的递送与梗死周围胶原蛋白的大量损失相关（对照动物中为32 +/- 5%比61 +/- 6%，p < 0.005）。结论在实验性心肌梗死中，通过导管经心内膜递送SDF-1 α来增强干细胞归巢的策略增加了梗死周围血管密度，不能改善心肌灌注，与梗死周围区域胶原蛋白的损失有关，并损害左心室功能。
Background Myocardial regeneration after myocardial infarction can occur via stem cell recruitment. Stromal cell-derived factor 1 alpha (SDF-1 alpha) has been shown to be critical for stem cell homing to injured tissue. Methods 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-1 alpha into the periinfarct myocardium (18 injections, 5 mu g 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. Results 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-1 alpha treated animals than in controls (349 +/- 17/mm(2) vs. 276 +/- 21/mm(2), p < 0.05). Myocardial perfusion (SPECT) did not change in either group. Ejection fraction and stroke volume (EMM) decreased in SDF-1 alpha 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-1 alpha 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). Conclusion A strategy to augment stem cell homing by catheter-based transendocardial delivery of SDF-1 alpha 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.