Retuerto Mauricio A, Schalch Paul, Patejunas Gerald, Carbray JoAnn, Liu Naxin, Esser Karyn, Crystal Ronald G, Rosengart Todd K
Evanston Northwest Healthcare, IL 60201, USA.
J Thorac Cardiovasc Surg. 2004 Apr;127(4):1041-9; discussion 1049-51. doi: 10.1016/j.jtcvs.2003.09.049.
Cell implantation into areas of myocardial infarction (cellular cardiomyoplasty) may be limited in efficacy because of the lack of blood supply to these areas of myocardium, resulting in early loss of transplanted cells. We therefore tested the hypothesis that pretreatment of infarcted myocardium with angiogenic therapy, followed by cell transplant, would be more effective than the application of either strategy alone.
Fischer 344 rats underwent left coronary artery ligation and injection of an adenovirus encoding VEGF 121, an empty expression cassette control vector, or saline solution. Capillary density in the infarcted region was determined in preliminary studies. Cardiomyocytes harvested from syngeneic Fischer rat fetuses were prelabeled and then injected directly into the infarct area 3 weeks after vector administration. Exercise treadmill testing was performed 2 weeks after cell transplantation, after which a cell viability index was calculated as the number of implanted (prelabeled) nuclei divided by the number of coadministered microspheres detected in sections of implanted myocardium.
Capillary density in the area of infarction was significantly greater in adenovirus encoding VEGF 121 compared with rats injected with saline solution (P =.001). The cell survival index was also greater in adenovirus encoding VEGF 121 compared with animals injected with empty expression cassette control or saline solution (P =.0045). Exercise tolerance was nearly doubled in animals receiving adenovirus encoding VEGF 121 3 weeks prior to cell implantation compared with animals receiving adenovirus encoding VEGF 121 or cells alone or those receiving adenovirus encoding VEGF 121 at the time of cell implantation (P <.001).
Pretreatment of an infarcted region of the heart with angiogenic mediators such as VEGF can enhance the efficacy of cellular cardiomyoplasty, presumably by creating a more favorable environment for the survival of transplanted cells.
由于心肌梗死区域缺乏血液供应，将细胞植入心肌梗死区域（细胞心肌成形术）的疗效可能会受到限制，这会导致移植细胞早期丢失。因此，我们检验了这样一个假设，即先用血管生成疗法预处理梗死心肌，然后进行细胞移植，会比单独应用这两种策略中的任何一种更有效。
对Fischer 344大鼠进行左冠状动脉结扎，并注射编码VEGF 121的腺病毒、空表达盒对照载体或生理盐水溶液。在初步研究中测定梗死区域的毛细血管密度。从同基因Fischer大鼠胎儿中收获的心肌细胞预先标记，然后在载体给药3周后直接注射到梗死区域。细胞移植2周后进行运动平板试验，之后计算细胞活力指数，即植入（预先标记）的细胞核数量除以在植入心肌切片中检测到的共同给药微球数量。
与注射生理盐水溶液的大鼠相比，编码VEGF 121的腺病毒处理的大鼠梗死区域的毛细血管密度显著更高（P = 0.001）。与注射空表达盒对照或生理盐水溶液的动物相比，编码VEGF 121的腺病毒处理的动物的细胞存活指数也更高（P = 0.0045）。与单独接受编码VEGF 121的腺病毒或细胞的动物，或在细胞植入时接受编码VEGF 121的腺病毒的动物相比，在细胞植入前3周接受编码VEGF 121的腺病毒的动物的运动耐量几乎提高了一倍（P < 0.001）。
用血管生成介质如VEGF预处理心脏梗死区域可提高细胞心肌成形术的疗效，这可能是通过为移植细胞的存活创造更有利的环境来实现的。
