Abstract 14372: MRI Assessment of Myocardial Perfusion, Viability and Function Following VEGF Revascularization in the Left Circumflex Coronary Artery Ligated Rabbit

Abstract

Strategies are being developed to limit reperfusion injury and enhance revascularization through gene therapy to promote angiogenesis in myocardial infarction. We hypothesized that the post myocardial infarcted heart treated with VEGF gene therapy would have improved left ventricular function and wall motion. Male rabbits were assigned into one of 5 groups: ligation with injection of pRTP801-VEGF plasmid complexed with cationic WSLP polymer, n = 14; ligation only, n = 10; ligation with WSLP polymer, n = 5; thoracotomy, n = 5; and unoperated control, n = 5. Ligated rabbits were completed by the occlusion of left circumflex coronary artery at mid-ventricle with a 6-0 prolene suture. VEGF treated rabbit received 5 injections of VEGF plasmid (0.2 ml each) at the epicardium over the ischemic transition zone. MR scanning was performed on pre-ligated rabbit 2 weeks prior to surgery, and repeated 7- and 30-days after the ligation. Myocardial perfusion was conducted by injecting Gd-BOPTA intravenously (0.15 mmol/kg) while non-trigger-gated radial scanning was performed to assess myocardial perfusion. Tissue perfusion rate was analyzed by a custom-built mpi2d software to obtain unslope indices of blood flow; and scar tissue was delineated and analyzed using the PSIR short-axis images and bullseye plot to obtain the infarct size, extent, and transmurality. Data are presented as mean±SEM, and were analyzed by ANOVA and ANCOVA. All measured cardiac parameters derived from the epi- and endocardial contours were similar among the left thoracotomy, normal and pre-ligated rabbits (p>0.05); or between the post-ligated and ligation with WSLP-injected hearts (p>0.05). Myocardial infarct size between 7- and 30-d VEGF-transfected rabbits were much improved (0.34±0.5 ml, 0.29±0.4 ml, respectively; p<0.05) when compared to the post-ligated rabbits (0.52±0.07 ml, 0.52±0.08 ml, respectively). Infarct extent as a percent of total left ventricular volume in the VEGF-transfected rabbits was also reduced (8.08±0.87%, 6.27±0.64% vs. 15.22±1.38%, 14.46±1.24%, respectively; p<0.05) when compared to the post-ligated rabbits. VEGF gene treatment causes significant reduction in infarct size and transmurality compared with the left circumflex coronary artery ligated rabbits.