Retuerto Mauricio A, Beckmann James T, Carbray JoAnn, Patejunas Gerald, Sarateanu Sorin, Kane Bonnie J, Smulevitz Beverly, McPherson David D, Rosengart Todd K
Evanston Northwestern Healthcare, Evanston, Ill, USA.
J Thorac Cardiovasc Surg. 2007 Feb;133(2):478-484.e2. doi: 10.1016/j.jtcvs.2006.08.073.
Improvements in ventricular function after cellular cardiomyoplasty appear to be limited by the poor survival of the cellular implants. Angiogenic pretreatment of infarcted myocardium may improve implanted cell survival and consequently myocardial function.
Fischer 344 rats underwent coronary artery ligation and injection of an adenovirus encoding vascular endothelial growth factor 121 or of saline solution at increasing intervals after ligation. Myocardial perfusion and mass preservation were assessed. On the basis of these data, four groups of animals underwent coronary ligation and adenovirus with or without syngeneic skeletal myoblast administration: (1) adenovirus at ligation and myoblasts 3 weeks later (n = 7), (2) saline solution at ligation and myoblasts 3 weeks later (n = 8), (3) saline solution at ligation and 3 weeks later (n = 8), and (4) saline solution at ligation and adenovirus with myoblasts 3 weeks later (n = 5). Left ventricular ejection fraction was analyzed by echocardiography before coronary ligation and 3 and 5 weeks later, after which cell survival was assessed in harvested tissues.
Myocardial infarct perfusion was at least 50% greater in animals treated with adenoviral vector than with saline solution immediately after ligation (P < .02). In comparison, delayed adenovirus administration did not significantly diminish infarct perfusion but resulted in decreased myocardial preservation (P < .05). Accordingly, adenovirus administration nearly tripled implanted myoblast survival relative to saline solution-treated animals (P = .004). Left ventricular ejection fraction was improved, however, only after cell implantation with adenovirus pretreatment (P = .027).
Angiogenic strategies can help to preserve myocardium jeopardized by acute coronary occlusions. Angiogenic pretreatment enhances the efficacy of cellular cardiomyoplasty.
细胞心肌成形术后心室功能的改善似乎受到细胞植入物存活率低的限制。梗死心肌的血管生成预处理可能会提高植入细胞的存活率，从而改善心肌功能。
对Fischer 344大鼠进行冠状动脉结扎，并在结扎后不同时间间隔注射编码血管内皮生长因子121的腺病毒或生理盐水。评估心肌灌注和质量保存情况。基于这些数据，四组动物接受冠状动脉结扎并给予或不给予同基因骨骼肌成肌细胞的腺病毒：（1）结扎时给予腺病毒，3周后给予成肌细胞（n = 7），（2）结扎时给予生理盐水，3周后给予成肌细胞（n = 8），（3）结扎时给予生理盐水，3周后再次给予生理盐水（n = 8），以及（4）结扎时给予生理盐水，3周后给予腺病毒并同时给予成肌细胞（n = 5）。在冠状动脉结扎前、结扎后3周和5周通过超声心动图分析左心室射血分数，之后评估收获组织中的细胞存活率。
结扎后立即接受腺病毒载体治疗的动物心肌梗死灌注比接受生理盐水治疗的动物至少高50%（P <.02）。相比之下，延迟给予腺病毒并没有显著减少梗死灌注，但导致心肌保存减少（P <.05）。因此，与生理盐水处理的动物相比，给予腺病毒使植入的成肌细胞存活率增加了近两倍（P =.004）。然而，只有在进行腺病毒预处理后植入细胞，左心室射血分数才得到改善（P =.027）。
血管生成策略有助于保护因急性冠状动脉闭塞而受损的心肌。血管生成预处理可提高细胞心肌成形术的疗效。
