A novel method of augmenting gene expression and angiogenesis in the normal and ischemic canine myocardium

This study presents a novel method that direct intramyocardial injection of low-dose plasmid DNA and microbubbles combined with insonation could further augment gene expression in normal and ischemic canine myocardium. Plasmids encoding enhanced green fluorescent protein (pEGFP) and hepatocyte growth factor (pHGF) (500???g) were individually mixed with 0.5?ml of microbubble solution (MB) and injected into the normal or acute ischemic canine myocardium. The dogs in the plasmid?+?MB/US group underwent insonation (US). Other dogs were randomly divided into three treatment groups: plasmid and insonation, plasmid and MB injection, and plasmid injection only. The EGFP and HGF mRNA expressions were assessed in the myocardium at the injection site and at sites 0.5 and 1?cm remote from the injection site. Compared to plasmid transfer alone, a mean 13.4-fold enhancement of gene expression was achieved in the EGFP?+?MB/US group at 48?h (p?<?0.01). HGF mRNA expression in ischemic zones was markedly elevated after 28?days, with a mean 9.0-fold enhancement in the HGF?+?MB/US group (p?<?0.01). EGFP protein expression was detected in the normal myocardium at 1?cm remote from the injection site in the EGFP?+?MB/US group. Similarly, HGF protein expression was detected in the ischemic myocardium at 0.5?cm remote from the injection site in the HGF?+?MB/US group. These findings indicate that the radius of gene expression was partly extended in the two plasmid?+?MB/US groups. The capillary density increased from 20.9?±?5.3/mm² in control myocardial infarction dogs without treatment to 126.7?±?38.2/mm² in the HGF?+?MB/US group (p?<?0.01). Taken together, the present data demonstrate that direct intramyocardial injection of an angiogenic gene and microbubbles combined with insonation can augment gene expression and angiogenesis. Consequently, this strategy may be a useful tool for gene therapy of ischemic heart disease.     

急性肺栓塞溶栓疗效及溶栓前后NT-proBNP的变化

目的:观察瑞替普酶对急性肺栓塞(APE)患者溶栓治疗的临床疗效及溶栓前后血浆N端B型尿钠肽前体(NT-proBNP)水平的变化及其临床意义。方法:42例符合溶栓治疗条件的APE患者给予瑞替普酶18mg+18mg静脉溶栓治疗,分别观察溶栓前及溶栓6h后患者临床表现、血浆NT-proBNP、肌钙蛋白T(cTnT)水平,溶栓12～24h复查超声心动图、CT肺动脉成像或核素肺灌注显像,评价临床疗效。结果:血管再通患者37例(88.1%),其NT-proBNP浓度和肺动脉压力均较溶栓前显著下降[(8 672.4±201.7)pg/ml︰(1 559.8±23.5)pg/ml,(52.82±17.34)mmHg︰(38.13±12.32)mmHg,1mmHg=0.133kPa;均P<0.01)],且NT-proBNP浓度下降幅度与肺动脉压下降幅度、右心室/左心室比值密切相关(r分别为0.61、0.54);溶栓前后cTnT水平差异无统计学意义。血管未通患者5例,其溶栓前后NT-proBNP、cTnT及肺动脉压力差异无统计学意义。结论:瑞替普酶对APE患者进行静脉溶栓治疗有较好的临床疗效和安全性,且动态检测NT-proBNP浓度可作为评价溶栓再灌注成功与否的有效指标。