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 perfusi on. To evaluate the efficiency of FGF2 delivery into an area that has been radio frequency (RF) ablated, we studied two catheter-based delivery method s, a direct injection system (Stiletto) and a combined RF ablation-delivery system (RF-PMR). Four groups (n = 3/group) of pigs received six transendoc ardial injections of I-125-FGF2/fluorescent microspheres with either the St iletto 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 h arvested. Intramyocardial deposition sites were located with UV light and i solated. 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). FGFS 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 ex plained by the differences in catheter design. The Stiletto has a retractab le needle and is optimized for intramyocardial delivery, whereas infusion f rom the RF-PMR device occurs at the endocardial surface and relies on chann els created during RF ablation. Overall, FGFS retention after transendocard ial intramyocardial delivery by the Stiletto or the RF-PMR system is signif icantly higher than previously observed for intracoronary, intravenous and intrapericardial delivery. In conclusion, the combination of RF ablation an d growth factor delivery using the RF-PMR system is feasible and efficient. (C) 2001 Wiley-Liss, Inc.