COMPARATIVE EFFECTS OF BASIC FIBROBLAST GROWTH-FACTOR AND VASCULAR ENDOTHELIAL GROWTH-FACTOR ON CORONARY COLLATERAL DEVELOPMENT AND THE ARTERIAL RESPONSE TO INJURY

Background We have shown that the angiogenic peptides basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) en hance canine coronary collateral development when administered for gre ater than or equal to 4 weeks. bFGF, a pluripotent mitogen of mesoderm ally derived cells, could theoretically exacerbate neointimal smooth m uscle cell hyperplasia, a fundamental component of atherosclerosis. VE GF, an endothelial cell-specific mitogen and vascular permeability fac tor, could have deleterious effects related to vascular hyperpermeabil ity. The present investigation had two aims: (1) to ascertain whether brief (7-day) systemic arterial treatment with bFGF or VEGF would impr ove myocardial collateral perfusion and (2) to determine whether these peptides induce neointimal accumulation in vivo. Methods and Results Dogs were subjected to ameroid-induced occlusion of the left circumfle x coronary artery and randomized to bFGF 1.74 mg (n=9), VEGF 0.72 mg ( n=9), or saline (n=10) as a daily left atrial bolus (days 10 to 16). A dditional dogs were randomized to VEGF 0.72 mg (n=6) or saline (n=5); however, treatment was delayed by 1 week. Coincident with the institut ion of treatment, all dogs underwent balloon denudation injury of the iliofemoral artery. bFGF markedly increased max collateral flow but di d not exacerbate neointimal accumulation. VEGF had no discernible effe ct on maximal collateral flow, but it exacerbated neointimal thickenin g after vascular injury. Conclusions Short-term treatment with bFGF en hanced collateral development without increasing neointimal accumulati on at sites of vascular injury. Although VEGF did not increase collate ral development as administered in this study, it significantly exacer bated neointimal accumulation. These data provide support for the clin ical investigation of bFGF in selected patients with ischemic heart di sease.