Background-We investigated the feasibility and efficacy of polyethylenimine (PEI) based human vascular endothelial growth factor-165 (hVEGF 165 ) gene transfer into human skeletal myoblasts (HSM) for cell based delivery to the infarcted myocardium. Methods and Results-Based on optimized transfection procedure using enhanced green fluorescent protein (pEGFP), HSM were transfected with plasmid-hVEGF 165 (phVEGF 165 ) carried by PEI (PEI-phVEGF 165 ) nanoparticles. The transfected HSM were characterized for transfection and expression of hVEGF 165 in vitro and transplanted into rat heart model of acute myocardial infarction (AMI): group-1ϭDMEM injection, group-2ϭ HSM transplantation, group-3ϭ PEI-phVEGF 165 -transfected HSM (PEI-phVEGF 165 myoblast) transplantation. A total of 48 rats received cyclosporine injection from 3 days before and until 4 weeks after cell transplantation. Echocardiography was performed to assess the heart function. Animals were sacrificed for molecular and histological studies on the heart tissue at 4 weeks after treatment. Based on optimized transfection conditions, transfected HSM expressed hVEGF 165 for 18 days with Ͼ90% cell viability in vitro. Apoptotic index was reduced in group-2 and group-3 as compared with group-1. Blood vessel density (ϫ400) by immunostaining for PECAM-1 in group-3 was significantly higher (Pϭ0.043 for both) as compared with group-1 and group-2 at 4 weeks. Regional blood flow (ml/min/g) in the left ventricular anterior wall was higher in group-3 (Pϭ0.043 for both) as compared with group-1 and group-2. Improved ejection fraction was achieved in group-3 (58.44Ϯ4.92%) as compared with group-1 (Pϭ0.004).
Conclusion-PEI
Background-Intracoronary ␥-and -radiation have reduced restenosis in animal models. In the clinical setting, the effectiveness of -emitters has not been studied in a broad spectrum of patients, particularly those receiving stents. Methods and Results-A prospective, randomized, sham-controlled study of intracoronary radiotherapy with the -emitting 32 P source wire, using a centering catheter and automated source delivery unit, was conducted. A total of 105 patients with de novo (70%) or restenotic (30%) lesions who were treated by stenting (61%) or balloon angioplasty (39%) received 0 (control), 16, 20, or 24 Gy to a depth of 1 mm in the artery wall. Angiography at 6 months showed a target site late loss index of 11Ϯ36% in radiotherapy patients versus 55Ϯ30% in controls (PϽ0.0001). A low late loss index was seen in stented and balloon-treated patients and was similar across the 16, 20, and 24 Gy radiotherapy groups. Restenosis (Ն50%) rates were significantly lower in radiotherapy patients at the target site (8% versus 39%; Pϭ0.012) and at target site plus adjacent segments (22% versus 50%; Pϭ0.018). Target lesion revascularization was needed in 5 radiotherapy patients (6%) and 6 controls (24%; PϽ0.05). Stenosis adjacent to the target site and late thrombotic events reduced the overall clinical benefit of radiotherapy. Conclusions--radiotherapy with a centered 32 P source is safe and highly effective in inhibiting restenosis at the target site after stent or balloon angioplasty. However, minimizing edge narrowing and late thrombotic events must be accomplished to maximize the clinical benefit of this modality. (Circulation. 2000;102:951-958.)
TMPFC is a quantitative index for the assessment of myocardial perfusion; it allows quantification of TMPG and may serve as a discerning tool to predict prognosis in patients undergoing primary angioplasty.
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