Effect of basic fibroblast growth factor on myocardial angiogenesis in dogs with mature collateral vessels.
OBJECTIVE
We sought to evaluate the potential of basic fibroblast growth factor (bFGF) to enhance coronary collateral perfusion in dogs with chronic single-vessel coronary occlusion. A secondary goal was to examine whether the salutary effects of bFGF treatment, previously proved effective in the short term, would be maintained in the long term (6 months).


BACKGROUND
bFGF, an angiogenic growth factor, is currently the subject of a Phase I trial in patients with ischemic heart disease. It has been shown to promote collateral development in dogs with progressive coronary occlusion when given during the period of natural collateralization. The effect of bFGF on quiescent collateral vessels, a subject of significant clinical importance, is uncertain.


METHODS
Dogs were subjected to ameroid-induced occlusion of the left circumflex coronary artery and randomized to bFGF (1.74 mg/day for 7 days), a regimen previously proved effective, or to saline solution. Maximal collateral perfusion was assessed 6 months later, and the dogs were reassigned to a course of bFGF or saline solution. Collateral perfusion was reevaluated after the second treatment course.


RESULTS
At 6 months, collateral function was identical in the groups treated initially with bFGF and saline solution. The subsequent course of bFGF did not induce further collateralization.


CONCLUSIONS
Although we previously demonstrated the salutary effects of this bFGF regimen in the short term (5 weeks), collateral flow in control dogs reached parity with that of bFGF-treated dogs after 6 months. bFGF did not induce further collateralization in dogs with mature collateral vessels, underscoring the priming role of ischemia for bFGF-induced collateral development.
Shou
M
M
Cardiology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892-1650, USA.
Thirumurti
V
V
Rajanayagam
S
S
Lazarous
D F
DF
Hodge
E
E
Stiber
J A
JA
Pettiford
M
M
Elliott
E
E
Shah
S M
SM
Unger
E F
EF
D000818:Animals; D003097:Collateral Circulation / Q000187:drug effects* / Q000502:physiology; D003331:Coronary Vessels / Q000502:physiology*; D004285:Dogs; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D006439:Hemodynamics; D008297:Male; D008863:Microspheres; D018919:Neovascularization, Physiologic / Q000187:drug effects* / Q000502:physiology; D013997:Time Factors
D016222:Fibroblast Growth Factor 2