Intracoronary basic fibroblast growth factor enhances myocardial collateral perfusion in dogs.
OBJECTIVE
In preparation for clinical trials of basic fibroblast growth factor (bFGF) to treat ischemic heart disease, we sought to identify a clinically feasible method of bFGF administration.


BACKGROUND
Basic FGF has been shown to promote collateral development after experimentally induced coronary occlusion; however, methods of bFGF delivery that have been shown to be effective in previous investigations would not be practical for clinical use.


METHODS
Four randomized, blinded, controlled investigations were conducted independently and sequentially in an established canine model. For all studies, dogs underwent operative placement of proximal left circumflex coronary artery ameroid constrictors. The four investigational regimens included: 1) bFGF by central venous bolus injection, 1,740 microg/day for one, two or seven days; 2) bFGF by intravenous infusion, 100 microg/kg body weight per day for seven days; 3) bFGF by pericardial instillation, 2,000 microg/day for 7 days; and 4) bFGF by intracoronary injection (Judkin's technique), 100 microg/kg per day for one or two days. Each substudy included a contemporaneous vehicle control group. Collateral perfusion (microspheres) was assessed during maximal coronary vasodilation during the first month after ameroid placement.


RESULTS
Maximal collateral perfusion in dogs that received intracoronary bFGF for two days exceeded that of concurrent control dogs by 31% (p < 0.01). Perfusion was not increased in dogs that received single-dose intracoronary bFGF. Basic FGF administration by central venous bolus injection, intravenous infusion and pericardial injection failed to enhance collateral perfusion.


CONCLUSIONS
Administration of bFGF by the intracoronary route, an intervention that is feasible in patients, augments collateral development in dogs. These data provide a rationale for clinical testing of intracoronary bFGF in ischemic heart disease.
Rajanayagam
M A
MA
Cardiology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892-1650, USA.
Shou
M
M
Thirumurti
V
V
Lazarous
D F
DF
Quyyumi
A A
AA
Goncalves
L
L
Stiber
J
J
Epstein
S E
SE
Unger
E F
EF
D000818:Animals; D003097:Collateral Circulation / Q000187:drug effects*; D003326:Coronary Circulation / Q000187:drug effects*; D003331:Coronary Vessels; D004195:Disease Models, Animal; D004285:Dogs; D016222:Fibroblast Growth Factor 2 / Q000008:administration & dosage / Q000494:pharmacology*; D007269:Injections, Intra-Arterial; D009203:Myocardial Infarction / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D014664:Vasodilation / Q000187:drug effects
D016222:Fibroblast Growth Factor 2