Intracoronary ultrasound targeted microbubble destruction enhances angiogenesis in canine with acute myocardial infarction

Abstract

Objective To investigate the effect of intracoronary ultrasound-targeted microbubble destruction (IC-UTMD) on angiogenesis in treatment of myocardial infarction (MI) . Methods Thirty-seven dogs were randomly divided into 4 groups: the control group (n=7, injected with normal saline via coronary artery) , intracoronary injection group (group IC, n=10, injected with angiogenin Ang1 plasmid via coronary artery) , IC-UTMD group (n=10, injected with Ang1 plasmid+UTMD) and IV-UTMD group (n=10, injected with Ang1 plasmid+UTMD) . Conventional ultrasound and myocardial perfusion imaging were performed before and after the treatment of MI. The distribution of FITC-labeled Ang1 in the myocardium was determined in 3 rats in each treatment group at 12 h. The myocardial samples were collected at 1 month. Masson staining was used to compare the degree of myocardial fibrosis at infarction lesions. Neovascularization was localized by factor Ⅷ and α-SMA. Ang1 mRNA and protein expression were determined by RT-PCR and Western blotting. Results: At 12 hours, the green fluorescence was the most intense in the IC-UTMD group (30.0%±3.5%) , which significantly increased compared with that in the IC group (15.2%±2.5%) or IV-UTMD group (20.9%±3.1%) , respectively (P<0.05) . At 1 month, the left ventricular end-diastolic dimension (LVEDD) increased slowly compared with that in the other groups, and the left ventricular ejection fraction (LVEF) significantly improved. The intensity ratio of myocardial perfusion and perfusion rate in the IC-UTMD group increased compared with that in the other groups (P<0.05) . Masson staining showed that the collagenous fibers were the most intense in the control group (60.0%±6.1%) , and significantly decreased in the IC-UTMD group. VIII and α-SMA localization suggested that neovascularization significantly increased in the IC-UTMD group compared with that in the other groups (P<0.05) . Ang1 mRNA and protein expression in the IC-UTMD group increased compared with that in the IC group and IV-UTMD group (P<0.05) . Conclusion IC-UTMD can increase the content of Ang1 plasmid in peripheral infraction lesion, such that it may enhance gene transfection, promote angiogenesis, and improve left ventricle remodeling. Compared with IV-UTMD, IC-UTMD is a more effective mode of transfection. Key words: Ultrasonography; Microbubble; Transfection; Coronary artery; Myocardial infarction