应变率显像及组织多普勒成像综合评价基因治疗慢性心肌缺血的实验研究

Experimental study on assessment of gene therapy in chronic myocardial ischemia by strain rate imaging and Doppler tissue imaging

目的探讨应变率显像及组织多普勒显像检测基因转染治疗心肌缺血的价值。方法健康家猪16头,在冠状动脉左旋支放置Ameroid环建立慢性心肌缺血模型,4周后治疗组注射携带血管内皮生长因子B基因的重组腺病毒液,对照组注射磷酸盐缓冲液,治疗后4周取心肌进行病理学检查。观察术前、置环后2周、4周及治疗后2周、4周左心室乳头肌水平短轴观后壁心肌收缩期速度(VS)、舒张早期速度(VE)、舒张晚期速度(VA)和内、外膜速度跨壁梯度的变化。结果缺血心肌较正常心肌速度梯度减小,色彩变暗。置环后2周,左室侧后壁心肌运动速度VS、VE较术前略下降但无统计学意义,局部心肌内、外膜速度跨壁梯度则明显降低(P<0.05);置环后4周,侧后壁心肌变薄,VS、VE明显减低(P<0.05),心肌内、外膜速度跨壁梯度进一步下降(P<0.05)。治疗后2周,基因转染组较对照组心肌运动速度无显著差异,而心肌内、外膜下速度跨壁梯度明显改善(P<0.05);治疗后4周,治疗组左心室侧后壁心肌运动速度较对照组增加(P<0.05),内、外膜下速度跨壁梯度持续改善(P<0.05)。结论心内、外膜速度跨壁梯度及心肌运动速度可准确评价慢性缺血心肌基因治疗前后节段性室壁厚度变化速率和室壁运动改善的情况,前者评价局部心功能的敏感性优于后者。

Objective To investigate the value of strain rate imaging and Doppler tissue imaging in detecting chronic myocardial ischemia before and after gene therapy. Methods Sixteen pigs were employed to build up the chronic myocardial ischemia model by placing ameroid constrictors on the proximal of the left circumflex coronary artery. Four weeks later, therapy group and control group were intramyocardially administrated recombinant adenovirus coding the vascular endothelial growth factors(Ad.VEGF-B) or phosphate buffer. Then after 4 weeks, their hearts were removed for pathological investigation. Pre-operation, 2 and 4 weeks after ameroid placement and 2 and 4 weeks after gene therapy, V S,V E,V A and myocardial velocity gradient(MVG) of lateral-posterior wall from short-axis view at the level of papillary muscles were measured. Results Compared with pre-operation, the V S and V E of lateral-posterior wall of the left ventricle slightly reduced without statistical significance 2 weeks after operation, but the MVG decreased significantly(P<(0.05)); Till 4 weeks, the V S and V E also significantly decreased(P<(0.05)) and the regional wall thinned. Two weeks after gene therapy, the myocardial velocity estimated by Doppler tissne imaging did not change in the therapy group and the control group, but MVG was significantly higher than that in control subjects(P<(0.05)); Four weeks post-therapy, V E of the therapy group was notably higher than that of the control group(P<(0.05)) and the MVG further increased(P<(0.05)). Conclusions The MVG and the velocity of myocardial motion can accurately detect changes of the wall thickness and velocity of regional ventricular wall motion in ischemic myocardium before and after gene therapy,the MVG is a more sensitive indicator of quantitative assessment of the regional myocardial function.