ANGIOGENESIS INDUCED BY ACIDIC FIBROBLAST GROWTH-FACTOR AS AN ALTERNATIVE METHOD OF REVASCULARIZATION FOR CHRONIC MYOCARDIAL-ISCHEMIA

Background. The effect of periadventitial administration of acidic fib roblast growth factor (FGF) on coronary miscriovascular reactivity and bloodflow was examined in the collateral-dependent and normally perfu sed myocardium. Methods. Ameroid constrictors were placed on the proxi mal left circumflex (LCx) coronary artery in 14 pigs. In seven pigs ac idic FGF (10 mu g) 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 mu m) were studied in a pressurized (40 mm Hg) no-flow state w ith video microscopy. Results. Relaxation mediated by beta-adrenocepto rs and induced by isoproterenol (p < 0.05), and endothelium-dependent relaxation induced by adenosine 5' diphosphate (ADP) (p < 0.05) of iso lated microvessels from the collateral-dependent LCx region were marke dly reduced compared with the respective responses of vessels from the normally perfused left anterior descending (LAD) artery region. Relax ation induced by the adenylate cyclase activator forskolin and the gua nylate 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. Bloodflow 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 fl ow in the LAD territory (0.89 +/- 0.09 ml/min/gm). Conclusions. The pe riadventitial delivery of acidic FGF normalizes vasomotor regulation b y beta-adrenergic and endothelium-dependent mechanisms and improves my ocardial perfusion to the collateral-dependent myocardium. This may ha ve implications regarding the treatment of patients with severe corona ry artery disease who are not ameneable to conventional methods of rev ascularization.