Intramyocardial and intracoronary basic fibroblast growth factor in porcine hibernating myocardium: a comparative study

Abstract

Objective Therapeutic angiogenesis is an alternative method of revascularization for end-stage coronary artery disease. We determined the effects of intramyocardial and intracoronary basic fibroblast growth factor 2 on myocardial blood flow and function in a porcine model of hibernating myocardium. Methods Twenty-four mini-swine with 90% left circumflex artery stenosis and documented hibernating myocardium by positron emission tomography and dobutamine stress echocardiography were randomized to intramyocardial basic fibroblast growth factor 2 at 0.6 μg/kg (mid-dose, n = 6, 30 injections/animal), 6 μg/kg (high-dose, n = 6, 30 injections/animal), or intramyocardial vehicle control (n = 6). The intracoronary group received 6 μg/kg basic fibroblast growth factor 2 (n = 6) into the right and left circumflex artery coronary arteries. Positron emission tomography and dobutamine stress echocardiography were repeated at 1 and 3 months. Results In the vehicle group, normalized left circumflex artery myocardial blood flow was 0.74 ± 0.04 at 1 month and 0.75 ± 0.07 at 3 months compared with 0.68 ± 0.03 at baseline. In the intracoronary group, myocardial blood flow was 0.71 ± 0.03 at 1 month and 0.72 ± 0.04 at 3 months compared with 0.67 ± 0.04 at baseline. In the mid group, myocardial blood flow was 0.73 ± 0.06 at 1 month and 0.85 ± 0.05 at 3 months ( P < .001) compared with 0.67 ± 0.04 at baseline. In the high group, myocardial blood flow was 0.81 ± 0.06 at 1 month and 0.83 ± .04 at 3 months ( P = .03) compared with 0.71 ± 0.02 at baseline. No significant improvements in ischemia were demonstrated in any of the groups by dobutamine stress echocardiography at 1 or 3 months. Conclusions In porcine hibernating myocardium, intramyocardial basic fibroblast growth factor 2 significantly improved regional myocardial blood flow 3 months after treatment. There was no significant change in function in any of the 4 groups. These data suggest that intramyocardial dosing of basic fibroblast growth factor 2 (0.6 μg/kg) may be an optimal dose for improving perfusion in the treatment of end-stage coronary artery disease.