EFFECT OF BASIC FIBROBLAST GROWTH-FACTOR ON ANGIOGENESIS IN THE INFARCTED PORCINE HEART

Administration of growth factors is emerging as a new therapeutic appr oach for the enhancement of collateral vessel formation in the ischemi c heart. We have investigated the effects of intramyocardial delivery of FGF-2 in the presence and absence of heparin on angiogenesis in a p orcine model of myocardial infarction. Yorkshire pigs were subjected t o myocardial infarction by the placement of an embolization coil in th e left anterior descending artery (n = 5). Four to five weeks after cr eation of an infarct, FGF-2 (10 mu g) alone or in complex with heparin , heparan sulfate, or heparin agarose beads was injected either into t he normal myocardium or along the infarct border area. Histologic eval uation of each injection site was performed 4 to 5 weeks post-injectio n. The effect of FGF-2 on angiogenesis was evaluated by determining th e number of capillaries (diameter < 20 mu m (and arterioles (> 20 mu m with tunica media) in each area observed. The number of capillaries w ere not affected by the treatment of FGF-2 both in normal myocardium a nd infarct border area. However, in the normal myocardium, the number of arterioles were increased with the treatment of FGF-2 alone (85 +/- 59 %, P < 0.04), FGF-2 plus heparin (281 +/- 193 %, P < 0.004) and FG F-2-coated heparin beads (241 +/- 141 %, P < 0.01), as compared to con trol. Delivery of FGF-2. into the infarct border area, also increased the number of arterioles when FGF-2 was given with heparin (736 +/- 15 4 %, P < 0.001) or heparin beads (700 +/- 109 %, P < 0.001), as compar ed to control. FGF-2 administered with heparin was the most effective method of enhancing angiogenesis as compared to FGF-2 alone, FGF-2 plu s heparan sulfate, or FGF-2 coated heparin agarose beads.