Basic fibroblast growth factor is upregulated in hibernating myocardium.
BACKGROUND
Ischemia is known to be a potent stimulus for the upregulation of angiogenic growth factors, such as basic fibroblast growth factor (bFGF). While previous investigations have shown that many angiogenic growth factors are upregulated in animal models of myocardial ischemia, the models used are limited in their ability to produce stable ischemia beyond a few weeks. Our laboratory uses a stable model of hibernating myocardium where later time points may be examined. Therefore, the goal of this study was to examine bFGF protein levels in the myocardium at baseline and 3 or 6 months following the onset of myocardial ischemia.


METHODS
A total of 18 miniswine were studied. Basal endogenous levels of bFGF were measured in control animals (n = 6) immediately following sacrifice, while 12 other pigs underwent a 90% left circumflex artery occlusion with documented hibernating myocardium by positron emission tomography ((13)N-ammonia) and dobutamine stress echocardiography. These animals were studied at 3 (n = 7) and 6 months (n = 5) postoperatively. At sacrifice, six 3 x 3 mm samples were harvested from the left circumflex (hibernating) myocardium. Basic FGF levels (picograms per microgram of protein) were determined using ELISA kits.


RESULTS
Basic FGF protein levels 3 months after the creation of hibernating myocardium were three times greater than in nonischemic control animals (P < 0.05), while levels at 6 months were increased sixfold compared to control animals (P < 0.05 versus both control and 3-month groups).


CONCLUSIONS
Endogenous bFGF production is upregulated at 3 and 6 months in hibernating porcine myocardium. The angiogenic effects of exogenous bFGF delivered into ischemic myocardium with varying levels of endogenous growth factors must be determined.
Scarborough
John E
JE
Division of Cardiovascular and Thoracic Surgery, Duke University Medical Center, Durham, North Carolina 27710, USA.
Smith
Monica L
ML
Domkowski
Patrick W
PW
Diodato
Luis H
LH
Pippen
Anne M
AM
Smith
Peter K
PK
Annex
Brian H
BH
Landolfo
Kevin P
KP
D000818:Animals; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism*; D008297:Male; D017682:Myocardial Stunning / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D012016:Reference Values; D013552:Swine; D013556:Swine, Miniature; D013997:Time Factors; D015854:Up-Regulation
D016222:Fibroblast Growth Factor 2