Several polypeptides with the potential to cause blood vessel growth (angiogenesis) have been sequenced and synthesized during the last few years. Our ultimate goal is to utilize these angiogenic 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. In previous investigations we administered basic fibroblast growth factor (BFGF) for durations of 4 to 9 weeks and demonstrated enhancement of coronary collateral blood flow in dogs by as much as 40%. The data also suggested that the angiogenic effect of BFGF is most pronounced during the period of maximal collateral development; however, treatment limited to this interval has not been studied.
The aim of this study was to determine if limited (7 day) exposure to BFGF would substantially increase collateral blood flow. Dogs were subjected to progressive ameroid- induced left circumflex occlusion, and randomized to receive BFGF 1.74 mg/d (n=9) or vehicle (n=10) as an intra-atrial bolus. Treatment was begun 10 days after ameroid placement and continued for 7 days. Maximal collateral blood flow (microsphere technique), assessed on days 10, 17, 24, and 38, diverged between groups. At the 38 day end of the study, collateral conductance was 3.72+/-0.68 vs. 2.55+/-.84 ml/min/100g/mmhg in treated and control dogs, respectively, (mean+/-SD, p<0.01). Mean arterial blood pressure and non-ischemic zone conductance were similar in the two groups. Thus, brief (7 day) systemic BFGF administration during the period of active collateral development progressively improved collateral blood flow: a 46% increase in collateral blood flow was apparent 21 days after cessation of treatment. More prolonged exposure to BFGF appears to be unnecessary. These findings may have important clinical implications: brief BFGF treatment in patients with refractory ischemia could enhance collateral blood flow while limiting potential deleterious side effects.
