Several polypeptides with the potential to cause blood vessel growth (angiogenesis) have been identified during the last few years. Our ultimate goal is to utilize these agent(s) to facilitate myocardial revascularization in patients with coronary heart disease. Basic fibroblast growth factor (bFGF) is one such peptide that may play an important role in coronary collateral formation. We studied the effect of bFGF on collateral blood flow in dogs subjected to gradual occlusion of the left circumflex coronary artery (LCX). In this experiment, the LCX was occluded gradually over a 2 to 3 week period by an ameroid constrictor applied to the proximal vessel, rendering its perfusion territory dependent on collateral vessels. Beginning 10 days after ameroid placement, bFGF 110 micrograms (N=8) or saline (N=ll) was given as a daily bolus injection directly into the LCX at a point just distal to the ameroid. Myocardial blood flow was determined with radiolabeled microspheres 3 days after ameroid placement and weekly for 5 weeks thereafter. Collateral flow was quantified during chromonar-induced maximal vasodilation and expressed as an ischemic/normal zone (IZ/NZ) ratio. After 2 weeks of treatment, the IZ/NZ ratio in bFGF treated dogs surpassed that of control dogs; final IZ/NZ blood flow ratios were 0.49+/-0.13 and 0.34+/-0.08 in the treated and control groups, respectively (p<0.05). We conclude that intracoronary bFGF enhances collateral blood flow in this canine model of single coronary occlusion.
