Vascular endothelial growth factor administration in chronic
myocardial ischemia.
Harada, Kazumasa, Menachem Friedman, John J. Lopez, Steven Y. Wang,
Jian Li, Pottumarthi V. Prasad, Justin D. Pearlman, Elazer R.
Edelman, Frank W. Sellke, and Michael Simons.
Vascular Biology Unit, Charles A. Dana Research Institute and
Harvard-Thorndike Laboratory, the Department of Medicine
(Cardiovascular Division), Department of Surgery, and Department of
Radiology, Beth Israel Hospital, Harvard Medical School, Boston, MA
02215, and Program in Health, Science and Technology. MIT, Cambridge,
MA 02139
APStracts 3:0104H, 1996.
Vascular endothelial growth factor (VEGF) is a potent mitogen capable
of stimulating angiogenesis. We examined the effect of VEGF
administration in a model of chronic porcine myocardial ischemia.
Nineteen pigs were instrumented with proximal circumflex coronary
artery (LCX) ameroid constrictors. In 8 animals VEGF (2 [mu]g) with
heparin (50 U) was administered extraluminally to the LCX myocardium
with an osmotic pump for 4 weeks and 11 other animals served as
controls. VEGF treated animals demonstrated higher flow in the LCX
territory during both rest and pacing compared to untreated controls
(rest: 1.35 +/- .1 vs. 0.80 +/- .09 ml/min/g; pacing: 2.01 +/- .37
vs. 1.01 +/- .07 ml/min/g, p<0.05, VEGF vs. controls). The
observed improvement in regional coronary flow in VEGF-treated
animals resulted in better preservation of endothelium-dependent
microvessel relaxation as well as fractional LV shortening in the LCX
territory during pacing in the VEGF-treated than in control animals
(% FSLCX controls: 7.1+/-2.6 vs. 3.6+/-2.0, rest vs. pacing; VEGF:
6.9+/-2.9 vs. 6.3+/-2.9, rest vs. pacing, p=NS). We conclude that
VEGF administration in a gradual coronary occlusion model in pigs
results in improvement of coronary flow and preservation of regional
hemodynamics in the compromised myocardium.
Received 14 July 1995; accepted in final form 11 September 1995.
APS Manuscript Number H659-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 20 March 96