Several polypeptides have been identified during the last few years with the ability to induce blood vessel development (angiogenesis), and we believe these agents have the potential to facilitate myocardial revascularization in patients with coronary heart disease. We have shown that the angiogenic peptide basic fibroblast growth factor (bFGF), a pluripotent mitogen of mesodermally-derived cells, enhances coronary collateral development in dogs when administered directly into the coronary circulation for 4 weeks, or into the systemic arterial circulation via left atrial injection for one or more weeks. More recently, we have found that comparable serum concentrations of bFGF are achieved following either intravenous or intra-atrial administration. Therefore, the aims of the present study were to determine 1) whether intravenous bFGF would enhance collateral blood flow and 2) the minimum duration of treatment required to improve collateral flow. Dogs were subjected to ameroid-induced occlusion of the left circumflex coronary artery and randomized to receive bFGF 1.74 mg/d as an intravenous bolus for 7 days (10-16 days after ameroid placement), bFGF for 2 days (days 14 and 16), or bFGF for 1 day (day 16). A control group received placebo. Collateral blood flow was assessed with microspheres during maximal coronary vasodilatation and expressed as a ratio of ischemic/normal zone (IZ/NZ) blood flow. Maximal collateral flow in dogs treated for 7 days was similar to that of dogs treated for 2 days and 1 day. Analyzed as a group, collateral flow in bFGF-treated dogs exceeded that of control dogs on day 17, with IZ/NZ ratios of 0.29plus/minus0.03 vs. 0.18plus/minus0.05 in treated and control groups, respectively (pless than 0.01). On day 24, collateral flow in bFGF-treated dogs exceeded that of controls, with IZ/NZ ratios of 0.34plus/minus0.03 vs. 0.27plus/minus0.05, respectively (pless than 0.05). These data are preliminary, but suggest that a single intravenous dose of bFGF improves collateral flow in dogs. Completion of the study will allow direct comparison between 1, 2, and 7 days of bFGF treatment.
