Intramyocardial delivery of FGF2 in combination with radio frequency transmyocardial revascularization

Therapeutic angiogenesis and percutaneous transmyocardial revascularization (PMR) are potentially synergistic modalities to improve myocardial perfusion. To evaluate the efficiency of FGF2 delivery into an area that has been radio frequency (RF) ablated, we studied two catheter-based delivery methods, a direct injection system (Stiletto) and a combined RF ablation-delivery system (RF-PMR). Four groups (n = 3/group) of pigs received six transendocardial injections of (125)I-FGF2/fluorescent microspheres with either the Stiletto or the RF-PMR catheter. RF-PMR injections were preceded by a 0.6 sec RF ablation step. After either 1 or 24 hr, hearts and other tissues were harvested. Intramyocardial deposition sites were located with UV light and isolated. Specific activity per site was expressed as a percentage of total activity injected per site corrected for quenching. Injection site recovery was high for both catheter systems (average = 88%) and systemic uptake was low (< 6% in the liver). FGF2 retention was significantly higher with the Stiletto than the RF-PMR catheter (Stiletto 1 hr 41% +/- 17%, 24 hr 26% +/- 10%, RF-PMR 1 hr 21% +/- 14%, 24 hr 13% +/- 8%; P < 0.001), principally explained by the differences in catheter design. The Stiletto has a retractable needle and is optimized for intramyocardial delivery, whereas infusion from the RF-PMR device occurs at the endocardial surface and relies on channels created during RF ablation. Overall, FGF2 retention after transendocardial intramyocardial delivery by the Stiletto or the RF-PMR system is significantly higher than previously observed for intracoronary, intravenous and intrapericardial delivery. In conclusion, the combination of RF ablation and growth factor delivery using the RF-PMR system is feasible and efficient. Cathet Cardiovasc Intervent 2001;53:429-434.