Angiogenesis induced by acidic fibroblast growth factor as an alternative method of revascularization for chronic myocardial ischemia

Abstract

Background. The effect of periadventitial administration of acidic fibroblast growth factor (FGF) on coronary microvascular reactivity and blood flow was examined in the collateral-dependent and normally perfused myocardium. Methods. Ameroid constrictors were placed on the proximal left circumflex (LCx) coronary artery in 14 pigs. In seven pigs acidic FGF (10 μg) was administered into the perivascular space of the proximal LCx artery by using an ethylene vinyl acetate copolymer slow release device. After 7 to 9 weeks coronary arterial microvessels (70 to 150 μm) were studied in a pressurized (40 mm Hg) no-flow state with video microscopy. Results. Relaxation mediated by β-adrenoceptors and induced by isoproterenol (p < 0.05), and endothelium-dependent relaxation induced by adenosine 5' diphosphate (ADP) (p < 0.05) of isolated microvessels from the collateral-dependent LCx region were markedly reduced compared with the respective responses of vessels from the normally perfused left anterior descending (LAD) artery region. Relaxation induced by the adenylate cyclase activator forskolin and the guanylate cyclase activator sodium nitroprusside were unaltered. Chronic treatment with acidic FGF normalized responses to isoproterenol (p < 0.001 versus nontreated LCx) and ADP (p < 0.001 versus nontreated LCx) in the collateral-dependent LCx region, whereas responses to forskolin and sodium nitroprusside were not changed. Blood flow in the collateral-dependent LCx region (0.49 ± 0.24 ml/min/gm) was less than that in the normally perfused LAD region (0.80 ± 0.24 ml/min/gm, p < 0.05). Treatment with acidic FGF improved perfusion in the LCx region (0.80 ± 0.06 ml/min/gm, p < 0.05) but did not significantly affect blood flow in the LAD territory (0.89 ± 0.09 ml/min/gm). Conclusions. The periadventitial delivery of acidic FGF normalizes vasomotor regulation by β-adrenergic and endothelium-dependent mechanisms and improves myocardial perfusion to the collateral-dependent myocardium. This may have implications regarding the treatment of patients with severe coronary artery disease who are not amenable to conventional methods of revascularization.