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- Title
Effects of intramyocardial pVEGF<sub>165</sub> delivery on regional myocardial blood flow: evidence for a spatial ‘delivery-efficacy’ mismatch.
- Authors
Radke, P. W.; Heinl-Green, A.; Frass, O. M.; Griesenbach, U.; Ferrari, S.; Geddes, D. M.; Alton, E. W. F. W.
- Abstract
The aim of this study was to determine the effects of direct intramyocardial pVEGF165 gene transfer on regional myocardial blood flow in a porcine model of chronic myocardial ischaemia. Pigs underwent placement of an ameroid constrictor around the left circumflex coronary artery. After 3 weeks, animals received direct intramyocardial injections of pVEGF165 (20 × 50?µl at 1?µg/µl, n=11) or a plasmid vector encoding chloramphenicol acetyltransferase (20 × 50?µl at 1?µg/µl, n=11) into a specified target area (TA) of the left lateral wall. At 3 weeks after gene transfer, animals underwent final evaluation including a systematic assessment of regional myocardial blood flow (MBF) under resting and stress conditions. In all, 20 animals (10 per group) reached final studies. There was no change in mean arterial blood pressure or Rentrop collateral score from gene delivery to final studies in either group, nor were there differences between study groups. MBF was significantly higher in the areas adjacent to the TA in the VEGF group under resting (P<0.001) and stress conditions (P<0.05). In addition, pVEGF165 gene transfer abolished flow differences between the adjacent areas and the septum. MBF was not different between study groups in the TA, the anterior wall, or the septum. In conclusion, direct intramyocardial pVEGF165 gene transfer significantly improves myocardial blood flow. However, this effect is limited to the myocardial segments adjacent to the area of gene delivery. These data, therefore, demonstrate a spatial ‘delivery-efficacy’ mismatch with implications for myocardial gene delivery sites and detection of treatment effects in vivo.Gene Therapy (2004) 11, 1249-1255. doi:10.1038/sj.gt.3302296 Published online 24 June 2004
- Subjects
VASCULAR endothelial growth factors; BLOOD flow; GENETIC transformation; CORONARY disease; HEART blood-vessels; CORONARY arteries; DRUG administration; THERAPEUTICS
- Publication
Gene Therapy, 2004, Vol 11, Issue 16, p1249
- ISSN
0969-7128
- Publication type
Article
- DOI
10.1038/sj.gt.3302296