OBJECTIVES

The effects of direct intramyocardial injection of the plasmid encoding vascular endothelial growth factor (phVEGF₁₆₅) in the border zone of myocardial infarct tissue in rat hearts were investigated.

BACKGROUND

Controversy exists concerning the ability of VEGF to induce angiogenesis and enhance coronary flow in the myocardium.

METHODS

Sprague-Dawley rats received a ligation of the left coronary artery to induce myocardial infarction (MI). At 33.1 ± 6.5 days, the rats were injected with phVEGF₁₆₅ at one location and control plasmid at a second location (500 μg DNA, n = 24) or saline (n = 16). After 33.1 ± 5.7 days, the hearts were excised for macroscopic and histologic analysis. Regional blood flow ratios were measured in 18 rats by radioactive microspheres.

RESULTS

phVEGF₁₆₅-treated sites showed macroscopic angioma-like structures at the injection site while control DNA and saline injection sites did not. By histology, 21/24 phVEGF₁₆₅-treated hearts showed increased focal epicardial blood vessel density and angioma-like formation. Quantitative morphometric evaluation in 20 phVEGF₁₆₅-treated hearts revealed 44.4 ± 10.5 vascular structures per field in phVEGF₁₆₅-treated hearts versus 21.4 ± 4.7 in control DNA injection sites (p < 0.05). Regional myocardial blood flow ratios between the injection site and noninfarcted area did not demonstrate any difference between phVEGF₁₆₅-treated hearts (0.9 ± 0.2) and saline-treated hearts (0.7 ± 0.1).

CONCLUSIONS

Injection of DNA for VEGF in the border zone of MI in rat hearts induced angiogenesis. Angioma formation at the injection sites did not appear to contribute to regional myocardial blood flow, which may be a limitation of gene therapy for this application.