Hargrave Barbara, Strange Robert, Navare Sagar, Stratton Michael, Burcus Nina, Murray Len, Lundberg Cathryn, Bulysheva Anna, Li Fanying, Heller Richard
Frank Reidy Research Center for Bioelectrics, Old Dominion University, Norfolk, Virginia, United States of America; School of Medical Diagnostics and Translational Sciences, College of Health Sciences, Old Dominion University, Norfolk, Virginia, United States of America.
Naval Medical Center Portsmouth, Portsmouth, Virginia, United States of America.
PLoS One. 2014 Dec 29;9(12):e115235. doi: 10.1371/journal.pone.0115235. eCollection 2014.
Myocardial ischemia can damage heart muscle and reduce the heart's pumping efficiency. This study used an ischemic swine heart model to investigate the potential for gene electro transfer of a plasmid encoding vascular endothelial growth factor for improving perfusion and, thus, for reducing cardiomyopathy following acute coronary syndrome. Plasmid expression was significantly greater in gene electro transfer treated tissue compared to injection of plasmid encoding vascular endothelial growth factor alone. Higher gene expression was also seen in ischemic versus non-ischemic groups with parameters 20 Volts (p<0.03), 40 Volts (p<0.05), and 90 Volts (p<0.05), but not with 60 Volts (p<0.09) while maintaining a pulse width of 20 milliseconds. The group with gene electro transfer of plasmid encoding vascular endothelial growth factor had increased perfusion in the area at risk compared to control groups. Troponin and creatine kinase increased across all groups, suggesting equivalent ischemia in all groups prior to treatment. Echocardiography was used to assess ejection fraction, cardiac output, stroke volume, left ventricular end diastolic volume, and left ventricular end systolic volume. No statistically significant differences in these parameters were detected during a 2-week time period. However, directional trends of these variables were interesting and offer valuable information about the feasibility of gene electro transfer of vascular endothelial growth factor in the ischemic heart. The results demonstrate that gene electro transfer can be applied safely and can increase perfusion in an ischemic area. Additional study is needed to evaluate potential efficacy.
心肌缺血会损害心肌并降低心脏的泵血效率。本研究使用缺血性猪心脏模型,来探究编码血管内皮生长因子的质粒进行基因电转染,以改善灌注,从而减少急性冠状动脉综合征后心肌病发生的可能性。与单独注射编码血管内皮生长因子的质粒相比,基因电转染处理的组织中质粒表达显著更高。在缺血组与非缺血组中,当脉冲宽度保持为20毫秒时,在20伏(p<0.03)、40伏(p<0.05)和90伏(p<0.05)参数下也观察到更高的基因表达,但在60伏时未观察到(p<0.09)。与对照组相比,接受编码血管内皮生长因子质粒基因电转染的组,其危险区域的灌注增加。所有组的肌钙蛋白和肌酸激酶均升高,表明治疗前所有组的缺血程度相当。使用超声心动图评估射血分数、心输出量、每搏输出量、左心室舒张末期容积和左心室收缩末期容积。在2周的时间段内,未检测到这些参数有统计学上的显著差异。然而,这些变量的趋势很有趣,为缺血心脏中血管内皮生长因子基因电转染的可行性提供了有价值的信息。结果表明,基因电转染可以安全应用,并可增加缺血区域的灌注。需要进一步研究来评估其潜在疗效。