Beeres Saskia L M A, Bax Jeroen J, Dibbets Petra, Stokkel Marcel P M, Zeppenfeld Katja, Fibbe Willem E, van der Wall Ernst E, Schalij Martin J, Atsma Douwe E
Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands.
J Nucl Med. 2006 Apr;47(4):574-80.
Intramyocardial injection of bone marrow cells has been proposed as a new therapeutic option for patients with chronic ischemic heart disease. We investigated whether autologous bone marrow-derived mononuclear cell injection into the myocardium of patients with drug-refractory ischemia reduces anginal symptoms, improves left ventricular (LV) function, increases myocardial perfusion, and alters the extent of scar tissue.
In 25 patients (mean age +/- SD, 64 +/- 10 y; 21 male) with drug-refractory angina pectoris (Canadian Cardiovascular Society [CCS] class III-IV), despite optimized medical therapy and without options for conventional revascularization, bone marrow was aspirated from the iliac crest. Mononuclear cell injections were targeted at myocardial regions with stress-induced ischemia on gated (99m)Tc-tetrofosmin SPECT. Anginal symptoms were reassessed at 3- and 6-mo follow-up. At baseline and 3-mo follow-up, gated (99m)Tc-tetrofosmin SPECT and (18)F-FDG SPECT were performed to assess LV function, LV volumes, myocardial perfusion (stress and rest, 17-segment model), and extent of scar tissue.
Mean CCS score improved from 3.4 +/- 0.6 at baseline to 2.3 +/- 0.6 at 3 mo (P < 0.01) and remained unchanged at 6 mo (2.3 +/- 0.6; P < 0.01 vs. baseline and P = not significant [NS] vs. 3 mo). Gated (99m)Tc-tetrofosmin SPECT demonstrated an increased LV ejection fraction (from 47.6% +/- 13.5% to 54.1% +/- 16.9%; P < 0.01) and a reduced LV end-systolic volume (from 81 +/- 68 mL to 75 +/- 70 mL; P < 0.01). Segmental regional wall thickening increased from 34% +/- 12% at baseline to 39% +/- 17% at 3-mo follow-up (P = 0.01). The number of segments with stress-inducible ischemia per patient decreased from 4.6 +/- 3.2 to 2.0 +/- 2.6 (P < 0.01). Both segmental stress and segmental rest score improved, although the improvement in stress score was more pronounced (decrease in segmental stress score 0.22 +/- 0.20 vs. decrease in segmental rest score 0.04 +/- 0.06; P < 0.01). Myocardial perfusion improved in 53% of the injected segments and in 13% of the noninjected segments (P < 0.01). The percentage of myocardial segments with some extent of scar remained unchanged at 3-mo follow-up (13% vs. 12%; P = NS).
Autologous bone marrow-derived mononuclear cell injection in patients with drug-refractory angina and chronic ischemia improves anginal symptoms, increases LV function, and predominantly enhances myocardial stress perfusion in injected segments, whereas the extent of myocardial scar tissue remains unchanged.
心肌内注射骨髓细胞已被提议作为慢性缺血性心脏病患者的一种新的治疗选择。我们研究了将自体骨髓来源的单个核细胞注射到药物难治性缺血患者的心肌中是否能减轻心绞痛症状、改善左心室（LV）功能、增加心肌灌注并改变瘢痕组织的范围。
对25例（平均年龄±标准差，64±10岁；21例男性）药物难治性心绞痛（加拿大心血管学会[CCS]III-IV级）患者进行研究，尽管进行了优化的药物治疗且没有传统血运重建的选择，从髂嵴抽取骨髓。单个核细胞注射针对门控（99m）锝-替曲膦SPECT显示有应激诱导缺血的心肌区域。在3个月和6个月随访时重新评估心绞痛症状。在基线和3个月随访时，进行门控（99m）锝-替曲膦SPECT和（18）F-氟代脱氧葡萄糖SPECT以评估左心室功能、左心室容积、心肌灌注（应激和静息，17节段模型）以及瘢痕组织的范围。
平均CCS评分从基线时的3.4±0.6改善至3个月时的2.3±0.6（P<0.01），6个月时保持不变（2.3±0.6；与基线相比P<0.01，与3个月相比P=无显著性差异[NS]）。门控（99m）锝-替曲膦SPECT显示左心室射血分数增加（从47.6%±13.5%至54.1%±16.9%；P<0.01），左心室收缩末期容积减少（从81±68 mL至75±70 mL；P<0.01）。节段性室壁增厚从基线时的34%±12%增加至3个月随访时的39%±17%（P=0.01）。每位患者应激诱导缺血节段的数量从4.6±3.2减少至2.0±2.6（P<0.01）。节段性应激和节段性静息评分均有所改善，尽管应激评分的改善更明显（节段性应激评分降低0.22±0.20，节段性静息评分降低0.04±0.06；P<0.01）。53%的注射节段和13%的未注射节段心肌灌注得到改善（P<0.01）。在3个月随访时，有一定程度瘢痕的心肌节段百分比保持不变（13%对12%；P=NS）。
对药物难治性心绞痛和慢性缺血患者进行自体骨髓来源的单个核细胞注射可改善心绞痛症状、增加左心室功能，并主要增强注射节段的心肌应激灌注，而心肌瘢痕组织的范围保持不变。
