Selective pressure-regulated retroinfusion of fibroblast growth factor-2 into the coronary vein enhances regional myocardial blood flow and function in pigs with chronic myocardial ischemia

OBJECTIVES: We sought to improve regional myocardial delivery and subsequent collateral perfusion induced by basic fibroblast growth factor-2 (FGF-2) using selective pressure-regulated retroinfusion of coronary veins for delivery. This hypothesis was tested in a newly developed pig model with percutaneous induction of chronic ischemia. BACKGROUND: Selective pressure-regulated retroinfusion of coronary veins is a catheter-based procedure that has been shown to provide effective regional delivery of drugs and gene vectors into ischemic myocardium. METHODS: A high-grade stenosis with subsequent progression to total occlusion within 28 days was induced by implanting a reduction stent graft into the left anterior descending artery (LAD). After seven days, a 30-min retroinfusion (anterior cardiac vein) was performed with (n = 7) or without (n = 7) 150 μg FGF-2 and compared with a 30-min antegrade infusion of 150 μg FGF-2 into the LAD (n = 7). Sonomicrometry to assess regional myocardial function at rest and during pacing, and microspheres to assess regional myocardial blood flow, were performed 28 days after implantation of the reduction stent. RESULTS: Retroinfusion of FGF-2 compared favorably with controls and with antegrade infusion of FGF-2 with regard to regional myocardial function at rest (18.5 ± 4.1% vs. 5.7 ± 2.9% vs. 7.9 ± 1.8%, respectively, p < 0.05) and during pacing. Regional myocardial blood flow was also higher in the LAD territory after retroinfusion of FGF-2 (1.07 ± 0.14 vs. 0.66 ± 0.07 vs. 0. 72 ± 0.17 ml·min^-1·g^-1, p < 0.05). CONCLUSIONS: Selective pressure-regulated retroinfusion increased tissue binding of FGF-2 and enhanced functionally relevant collateral per fusion compared with antegrade intracoronary delivery in pigs with chronic myocardial ischemia.