REDUCTION IN MYOCARDIAL INFARCT SIZE BY BASIC FIBROBLAST GROWTH-FACTOR AFTER TEMPORARY CORONARY-OCCLUSION IN A CANINE MODEL

Background Basic fibroblast growth factor (bFGF) has been shown to red uce infarct size in canine acute myocardial infarction; however, the m echanism of tissue salvage remains uncertain. We evaluated the effect of bFGF on infarct size in a model of acute infarction in which corona ry occlusion was followed by prolonged reperfusion and sought to deter mine whether reperfusion attenuates the stimulus for myocardial neovas cularization. Methods and Results Anesthetized dogs undergoing 4-hour balloon occlusion of the left anterior descending coronary artery were treated with intracoronary bFGF (n=8) or vehicle (n=6). Ten-microgram doses of bFGF were administered 10 minutes after occlusion and again immediately before reperfusion. Left ventriculograms were obtained bef ore occlusion, after reperfusion, and preceding euthanasia on day 7. I nfarct size, expressed as a percentage of the area at risk, was reduce d in bFGF-treated dogs (13.7+/-2.1% versus 28+/-3.4%; P=.002). Changes in left ventricular ejection fraction, capillary density, and cellula r proliferation-assessed immunohistochemically with factor VIII and pr oliferating cell nuclear antigen antibodies-were similar in both group s. To assess coronary vasomotor responses to bFGF, a separate hemodyna mic study was performed in five anesthetized nonischemic dogs in which incremental bFGF doses up to 100 mu g induced no vasodilator response . Conclusions Treatment with bFGF was associated with a reduction in i nfarct size without hemodynamic effects or evidence of neovascularizat ion. These data suggest that bFGF mediates myocardial salvage independ ently of angiogenesis and that reperfusion after infarction may attenu ate the stimulus for neovascularization.