Angiogenic-induced enhancement of collateral blood flow to ischemic myocardium by vascular endothelial growth factor in dogs.
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.


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.
Banai
S
S
Cardiology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Md. 20892.
Jaklitsch
M T
MT
Shou
M
M
Lazarous
D F
DF
Scheinowitz
M
M
Biro
S
S
Epstein
S E
SE
Unger
E F
EF
D000818:Animals; D003097:Collateral Circulation / Q000187:drug effects* / Q000502:physiology; D003326:Coronary Circulation / Q000187:drug effects / Q000502:physiology*; D003331:Coronary Vessels / Q000187:drug effects*; D004285:Dogs; D016228:Endothelial Growth Factors / Q000494:pharmacology* / Q000502:physiology; D004730:Endothelium, Vascular / Q000187:drug effects; D005260:Female; D008222:Lymphokines / Q000494:pharmacology* / Q000502:physiology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D017202:Myocardial Ischemia / Q000188:drug therapy* / Q000503:physiopathology; D009389:Neovascularization, Pathologic; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors