Grøgaard Haakon K, Sigurjonsson Olafur E, Brekke Magne, Kløw Nils E, Landsverk Kirsti Solberg, Lyberg Torstein, Eriksen Morten, Egeland Torstein, Ilebekk Arnfinn
Institute for Experimental Medical Research (IEMR), Ulleval University Hospital, N-0407 Oslo, Norway.
Cardiovasc Revasc Med. 2007 Jan-Mar;8(1):21-7. doi: 10.1016/j.carrev.2006.09.001.
The purpose of the present study was to compare the efficacy of intracoronary and intravenous injection of autologous progenitor cells for homing to the acutely infarcted but reperfused myocardium in pigs.
Myocardial infarction was induced in 11 anesthetized pigs by 60-min balloon inflation in the mid LAD. After balloon deflation, reperfusion was verified and autologous CD31(+) progenitor cells, or bone marrow mononuclear cells, labeled with PKH67, were injected either intracoronarily (n=6) or intravenously (n=3). By autopsy, 4-5 days after induction of infarction, tissue from the heart and other organs was obtained for fluorescence microscopy.
In the heart, PKH(+) cells were detected throughout the reperfused infarcted myocardium, and the number of PKH(+) cells was significantly higher after intracoronary than after intravenous injection (3.2+/-0.55 vs. 0.33+/-0.17 cells/high-power field/10(6) cells injected, P=.01). Few PKH(+) cells were detected in the spleen, lung, mesenteric lymph node, and bone marrow. In an additional animal with a coil placed in the mid LAD, progenitor cells were not detected in the infarcted myocardium or in the normal myocardium.
Autologous mononuclear and CD31(+) cells from bone marrow accumulated in the infarcted myocardium when injected intracoronarily or intravenously after established reperfusion, and the accumulation of cells was significantly greater after intracoronary injection than after intravenous injection. Accumulation of PKH(+) cells did not appear in the normal myocardium or in the nonreperfused infarcted myocardium. PKH(+) cells were detected in spleen, lung, and bone marrow but to a lesser degree than in the infarcted myocardium.
本研究旨在比较冠状动脉内注射与静脉注射自体祖细胞归巢至猪急性梗死但已再灌注心肌的疗效。
对11只麻醉猪通过在左前降支中段球囊扩张60分钟诱导心肌梗死。球囊放气后,确认再灌注,将用PKH67标记的自体CD31(+)祖细胞或骨髓单个核细胞通过冠状动脉内注射(n = 6)或静脉注射(n = 3)。在梗死诱导后4 - 5天进行尸检,获取心脏和其他器官的组织用于荧光显微镜检查。
在心脏中,在整个再灌注梗死心肌中均检测到PKH(+)细胞,冠状动脉内注射后PKH(+)细胞数量显著高于静脉注射(3.2±0.55对0.33±0.17个细胞/高倍视野/10(6)个注射细胞,P = 0.01)。在脾脏、肺、肠系膜淋巴结和骨髓中检测到的PKH(+)细胞很少。在另一只在左前降支中段放置线圈的动物中,在梗死心肌或正常心肌中均未检测到祖细胞。
在建立再灌注后冠状动脉内或静脉注射时,来自骨髓的自体单个核细胞和CD31(+)细胞积聚在梗死心肌中,冠状动脉内注射后细胞积聚显著多于静脉注射。PKH(+)细胞未出现在正常心肌或未再灌注的梗死心肌中。在脾脏、肺和骨髓中检测到PKH(+)细胞,但程度低于梗死心肌。