309 MR assessment of myocardial perfusion, viability and function after intramyocardial transfer of plasmid expressing two isoforms of hepatocyte growth factor in swine model

Abstract

Methods In this study the HGF gene was injected intramyocardially in reperfused infarction (2 hr occlusion), for the purpose of evaluating this strategy as a therapeutic approach for protection from LV remodeling. MR imaging was performed at 3 days and 7–8 weeks on a 1.5-T MR clinical scanner (Philips Medical Systems). First pass perfusion, delayed contrast enhancement and cine MR imaging was used in the evaluation. Triphenyltetrazolium chloride (TTC) and histopathological (Masson's trichrome and Biotinylated Bandeiria simplicifolia isolectin B4) stains were utilized to quantify vascular density and myocardial viability. Results The peak signal intensity (SI), extents of hypoenhanced ischemic myocardium and max upslope data in the two groups were not significantly different at 3 days. At 7–8 weeks peak signal intensity was higher and maximum upslope data was steeper in treated animals compared to controls. The extent of hyperenhanced scar was significantly larger in control (13.2 ± 1.6% LV) compared with HGF treated (7.0 ± 0.5% LV) animals. TTC analysis also showed that the extent of scar tissue was significantly larger in control (12.0 ± 1.7%) compared with treated (6.6 ± 0.7% LV, P = 0.04) animals. There was no significant difference between the extent of hyperenhanced scar on MRI and TTC (P = 0.32). The infarction tended to be non-transmural with a residual thicker wall in treated compared with control animals both on MR images and TTC. Control animals showed evidence of LV remodeling, which was reflected by increased end systolic volumes and decline in ejection fraction. Treated animals showed a decrease from in end diastolic (2.15 ± 0.12 to 1.82 ± 0.12, P = 0.008) and end systolic (1.33 ± 0.07 to 1.00 ± 0.08, P = 0.001) volumes. They also showed increased ejection fraction (40.3 ± 1.3 to 45.7 ± 1.8, P = 0.001).