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

Academic Article
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publication date

  • April 1999

abstract

  • In a canine model of permanent coronary occlusion it has been shown that basic fibroblast growth factor (bFGF) reduced infarct size and this was associated with an increase in myocardial capillary density a week after infarction. In a preliminary work from our own laboratory using a model of occlusion followed by prolonged reperfusion we observed a similar reduction in infarct 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 myocardial neovascularization would be excluded as a mechanism by the short duration of the study. Seventeen mongrel dogs were anesthetized and the heart was exposed through a left thoracotomy. The left anterior descending (LAD) coronary artery was isolated and occluded for 3 h. Fifteen min after LAD occlusion dogs received bFGF 20 microg of bFGF (n=6) or placebo (n=11) by intracoronary 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 the dogs were euthanized and infarct size was measured. Regional CBF was similar between the two groups of dogs throughout all the study. The SF was similar between the two groups prior the onset of ischemia and at the beginning 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 infarct size, normalized for the area at risk was 14.2+/-5.2% in bFGF group vs 25.8+/-8.2% in placebo group (P=0.015). In summary we have demonstrated that bFGF significantly limits myocardial necrosis after acute coronary occlusion, and that this occurred without an increase in regional myocardial perfusion and within a period of time too brief for angiogenesis to have occurred. By exclusion, it appears that the salutary effect of bFGF is likely to be mediated by a cellular mechanism. The mechanism or mechanisms responsible for myocardial salvage by bFGF may have significant potential to be exploited in the clinical arena as the basis for therapies to protect the acutely ischemic myocardium.