Circulation, Vol 89, 2183-2189, Copyright © 1994 by American Heart Association
S Banai, MT Jaklitsch, M Shou, DF Lazarous, M Scheinowitz, S Biro, SE Epstein and EF Unger
BACKGROUND: Vascular endothelial growth factor (VEGF) is an endothelial
cell-specific mitogen that is angiogenic in vitro and in vivo. It has been
hypothesized that VEGF plays a role in myocardial collateral formation;
however, the effects of VEGF on collateral flow to ischemic myocardium are
unknown. METHODS AND RESULTS: We studied the effect of VEGF on collateral
blood flow in dogs subjected to gradual occlusion of the left circumflex
coronary artery (LCx). Beginning 10 days after placement of an
LCx-constricting device, VEGF 45 micrograms (n = 9) or saline (n = 12) was
administered daily via an indwelling catheter in the distal LCx, at a point
just beyond the occlusion. Treatment was maintained for 28 days. Collateral
blood flow was determined with microspheres 7 days before treatment,
immediately before treatment (day 0), and 7, 14, 21, and 28 days into the
treatment period. Collateral blood flow was quantified during
chromonar-induced maximal vasodilation and expressed as a collateral
zone/normal zone (CZ/NZ) ratio. Treatment with VEGF was associated with a
40% increase in collateral blood flow (final CZ/NZ blood flow ratios of
0.49 +/- 0.06 and 0.35 +/- 0.02 in the VEGF-treated and control groups,
respectively, P = .0037) as well as an 89% increase in the numerical
density of intramyocardial distribution vessels (> 20 microns diameter)
in the CZ (6.6 +/- 1.4 versus 3.5 +/- 0.7 vessels/mm2 in VEGF-treated and
control dogs, respectively, P < .05). CONCLUSIONS: We conclude that
intracoronary VEGF enhances the development of small coronary arteries
supplying ischemic myocardium, resulting in marked augmentation of maximal
collateral blood flow delivery. These results demonstrate the feasibility
of pharmacological enhancement of collateral growth and suggest a new
therapeutic approach for the treatment of myocardial ischemia.
ARTICLES
Angiogenic-induced enhancement of collateral blood flow to ischemic myocardium by vascular endothelial growth factor in dogs
Cardiology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Md. 20892.
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