Reduction in myocardial infarct size by basic fibroblast growth factor following coronary occlusion in a canine model

In a canine model of permanent coronary occlusion it has been shown that ba sic fibroblast growth factor (bFGF) reduced infarct size and this was assoc iated with an increase in myocardial capillary density a week after infarct ion. In a preliminary work from our own laboratory using a model of occlusi on followed by prolonged reperfusion we observed a similar reduction in inf arct size without evidence of myocardial neovascularization, The aim of the present investigation was to evaluate the effects of bFGF on infarct size and blood flow to the infarct zone in an acute experiment in which myocardi al neovascularization would be excluded as a mechanism by the short duratio n of the study. Seventeen mongrel dogs were anesthetized and the heart was exposed through a left thoratocomy. The left anterior descending (LAD) coro nary artery was isolated and occluded for 3 h. Fifteen min after LAD occlus ion dogs received bFGF 20 mu g of bFGF (n=6) or placebo (n=11) by intracoro nary injection infused over 5 min. We measured heart rate, aortic pressure, regional coronary blood flow (CBF), regional shortening fraction (SF) at 1 , 30 and 180 min of occlusion, then the LAD was reperfused for 5 min then t he dogs were euthanized and infarct size was measured. Regional CBF was sim ilar between the two groups of dogs throughout all the study. The SF was si milar between the two groups prior the onset of ischemia and at the beginni ng of the ischemic period. After 180 min of ischemia SF was 2.7+/-4.1% for bFGF and -3.1+/-4.7 for placebo (P=0.049), and during reperfusion SF was 3. 4+/-4.6% for bFGF and 0.4+/-1.0% for placebo treated dogs (P=0.023). The in farct size, normalized for the area at risk was 14.2+/-5.2% in bFGF group v s 25.8+/-8.2% in placebo group (P=0.015). In summary we have demonstrated t hat bFGF significantly limits myocardial necrosis after acute coronary occl usion, and that this occurred without an increase in regional myocardial pe rfusion and within a period of time too brief for angiogenesis to have occu rred. By exclusion, it appears that the salutary effect of bFGF is likely t o be mediated by a cellular mechanism. The mechanism or mechanisms responsi ble for myocardial salvage by bFGF may have significant potential to be exp loited in the clinical arena as the basis for therapies to protect the acut ely ischemic myocardium. (C) 1999 Elsevier Science ireland Ltd. All rights reserved.