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(Circulation. 1996;94:1927-1933.)
© 1996 American Heart Association, Inc.
Articles |
Reduction in Myocardial Infarct Size by Basic Fibroblast Growth Factor After Temporary Coronary Occlusion in a Canine Model
the Experimental Thrombosis Laboratory, Joseph J. Jacobs Center for Thrombosis and Vascular Biology, Department of Cardiology, and Department of Biomedical Engineering (D.G.V.), The Cleveland Clinic Foundation, Cleveland, Ohio.
Correspondence to Eric J. Topol, MD, Department of Cardiology (F-25), The Cleveland Clinic Foundation, 9500 Euclid Ave, Cleveland, OH 44195. E-mail topole@cesmtp.ccf.org.
Background Basic fibroblast growth factor (bFGF) has been shown to reduce infarct size in canine acute myocardial infarction; however, the mechanism of tissue salvage remains uncertain. We evaluated the effect of bFGF on infarct size in a model of acute infarction in which coronary occlusion was followed by prolonged reperfusion and sought to determine whether reperfusion attenuates the stimulus for myocardial neovascularization.
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 before occlusion, after reperfusion, and preceding euthanasia on day 7. Infarct size, expressed as a percentage of the area at risk, was reduced in bFGF-treated dogs (13.7±2.1% versus 28±3.4%; P=.002). Changes in left ventricular ejection fraction, capillary density, and cellular proliferation—assessed immunohistochemically with factor VIII and proliferating cell nuclear antigen antibodies—were similar in both groups. To assess coronary vasomotor responses to bFGF, a separate hemodynamic study was performed in five anesthetized nonischemic dogs in which incremental bFGF doses up to 100 µg induced no vasodilator response.
Conclusions Treatment with bFGF was associated with a reduction in infarct size without hemodynamic effects or evidence of neovascularization. These data suggest that bFGF mediates myocardial salvage independently of angiogenesis and that reperfusion after infarction may attenuate the stimulus for neovascularization.
Key Words: growth substances • myocardial infarction • vessels • vasodilation
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