Intracoronary basic fibroblast growth factor enhances myocardial collateral perfusion in dogs

OBJECTIVES In preparation for clinical trials of basic fibroblast growth fa ctor (bFGF) to treat ischemic heart disease, we sought to identify a clinic ally feasible method of bFGF administration. BACKGROUND Basic FGF has been shown to promote collateral development after experimentally induced coronary occlusion; however, methods of bFGF delive ry that have been shown to be effective in previous investigations would no t be practical for clinical use. METHODS Four randomized, blinded, controlled investigations were conducted independently and sequentially in an established canine model. For:all stud ies, dogs underwent operative placement of proximal left circumflex: corona ry artery ameroid constrictors. The four investigational regimens included: 1) bFGF by central venous bolus injection, 1,740 mu g/day for one, two or seven days; 2) bFGF by intravenous infusion, 100 mu g/kg body weight per da y for seven days; 3) bFGF by pericardial instillation, 2,000 mu g/day for 7 days; and 4) bFGF by intracoronary injection (Judkin's technique); 100 mu g/kg per day for one or two days. Each substudy included a contemporaneous vehicle control group. Collateral perfusion (microspheres) was assessed dur ing maximal coronary vasodilation during the first month after ameroid plac ement. RESULTS Maximal collateral perfusion in dogs that received intracoronary bF GF for two days exceeded that of concurrent control dogs by 31% (p < 0.01). Perfusion was not increased in dogs that received single-dose intracoronar y bFGF. Basic FGF administration by central venous bolus injection, intrave nous infusion and pericardial injection failed to enhance collateral perfus ion. CONCLUSIONS Administration of bFGF by the intracoronary route, an intervent ion that is feasible in patients, augments collateral development:in dogs. These data provide a rationale for clinical testing of intracoronary bFGF i n ischemic heart disease. (J Am Coll Cardiol 2000;35: 519-26) (C) 2000 by t he American College of Cardiology.