用门控心肌显像评价重组腺病毒-肝细胞生长因子治疗缺血性心脏病

摘要

Objective Hepatocyte growth factor (HGF) has multipotent actions mediated by cMesenchymal epithelial transition factor (Met) receptor. Preclinical studies in animal models of myocardial ischemia demonstrated that treatment with HGF could benefit myocardial perfusion, cardiac remodeling, angiogenesis and myocardial function. This study used gated 99Tcm-methoxyisobutylisonitrile (MIBI) myocardial perfusion imaging (G-MPI) to assess the early treatment effectiveness of adenovirus HGF (Ad-HGF) directly administered in ischemic heart disease (IHD) patients. Methods Eighteen patients with IHD were divided into 3 groups receiving low dose [5×108 plaque forming unit (PFU)/site], medium(1.5×109 PFU/site) and high dose (5×109 PFU/site) of Ad-HGF. And the Ad-HGF was injected at 10 sites in each patient. Rest G-MPI was performed before and after treatment for myocardial perfusion and left ventricular function measurement. Stata 7.0 was used to analyse the data. Results (1) After Ad-HGF, myocardial perfusion was improved in 3/6,5/6 and 6/6 patients in low, medium and high dosage groups. The dosage of AD-HGF was closely correlated with the improvement of myocardial perfusion (X2=4.34, P＜0.05).(2) Left ventricular ejection fraction (LVEF) was significantly increased [(50.1±6.4)% vs (58.7±5.6)%, t=6.1, P＜0.01], end-diastolic volume [EDV, (137.7±33.2)ml vs (123.7±32.7)ml] and end-systolic volume [ESV, (70.2±22.4)ml vs (51.9±14.9)ml] were significantly reduced.(3) The LVEFs were increased in all groups, and the LVEF improvement in the high dosage group [(8.6±5.9)%] was significantly greater than the other two groups [(4.3±1.2)%,(6.8±5.7)%]. The difference of post-treatment improvement on LVEF between the low and medium dosage groups was not significant. The dosage of Ad-HGF was closely correlated with the improvement of LVEF (t=0.67, P＜0.01). Conclusion G-MPI is a reliable method for evaluating the early effectiveness of direct myocardial administration of Ad-HGF in the treatment of IHD.%目的 探讨99Tcm-甲氧基异丁基异腈(MIBI)静息门控心肌灌注显像(G-MPI)评价重组腺病毒-肝细胞生长因子(Ad-HGF)心肌内直接注射对缺血性心脏病早期治疗的价值.方法 18例冠心病患者根据随机分组表分为小、中、大剂量Ad-HGF治疗组,分别接受5×108,1.5×109,5×109空斑形成单位(PFU)/点(均分10点注射)的Ad-HGF心肌内直接注射.所有患者于治疗前后分别行静息G-MPI,以评价心功能和注射部位心肌血流灌注的变化.采用Stata 7.0软件进行统计学处理.结果 (1)与治疗前相比,小剂量组中有3例、中剂量组中有5例、大剂量组中有6例患者于Ad-HGF注射区域出现心肌血流灌注的改善,改善情况与注射剂量有量-效关系(X2=4.34, P＜0.05).(2)18例患者治疗前静息左心室射血分数(LVEF)、左心室舒张末期容积(EDV)和收缩末期容积(ESV)分别为(50.1±6.4)%,(137.7±33.2)和(70.2±22.4)ml;治疗后分别为(58.7±5.6)%,(123.7±32.7)和(51.9±14.9)ml.LVEF治疗后较治疗前有增加(t=6.1, P＜0.01),EDV和ESV则明显降低(t值分别为5.9,6.4,P均＜0.01).(3)低、中、高剂量Ad-HGF治疗组治疗前LVEF为(50.3±4.9)%,(52.0±5.4)%和(47.8±8.8)%,治疗后LVEF为(54.7±4.1)%,(58.8±3.9)%和(62.5±6.3)%.治疗前后LVEF的差值分别为(4.3±1.2)%,(6.8±5.7)%和(8.6±5.9)%,各组治疗后LVEF均增加:其中高剂量组的增加幅度明显高于中、低剂量组(t=3.3, P＜0.05; t=4.3, P＜0.01),中、低剂量组之间差异无统计学意义(t=1.1, P＞0.05).治疗前后LVEF的变化幅度与注射Ad-HGF剂量有量-效关系(Spearman相关系数为0.67, P＜0.01).结论 G-MPI可用于评价Ad-HGF心肌内直接注射治疗缺血性心脏病早期疗效.