Intramyocardial and intracoronary basic fibroblast growth factor in porcine hibernating myocardium: a comparative study.
OBJECTIVE
Therapeutic angiogenesis is an alternative method of revascularization for end-stage coronary artery disease. We determined the effects of intramyocardial and intracoronary basic fibroblast growth factor 2 on myocardial blood flow and function in a porcine model of hibernating myocardium.


METHODS
Twenty-four mini-swine with 90% left circumflex artery stenosis and documented hibernating myocardium by positron emission tomography and dobutamine stress echocardiography were randomized to intramyocardial basic fibroblast growth factor 2 at 0.6 microg/kg (mid-dose, n = 6, 30 injections/animal), 6 microg/kg (high-dose, n = 6, 30 injections/animal), or intramyocardial vehicle control (n = 6). The intracoronary group received 6 microg/kg basic fibroblast growth factor 2 (n = 6) into the right and left circumflex artery coronary arteries. Positron emission tomography and dobutamine stress echocardiography were repeated at 1 and 3 months.


RESULTS
In the vehicle group, normalized left circumflex artery myocardial blood flow was 0.74 +/- 0.04 at 1 month and 0.75 +/- 0.07 at 3 months compared with 0.68 +/- 0.03 at baseline. In the intracoronary group, myocardial blood flow was 0.71 +/- 0.03 at 1 month and 0.72 +/- 0.04 at 3 months compared with 0.67 +/- 0.04 at baseline. In the mid group, myocardial blood flow was 0.73 +/- 0.06 at 1 month and 0.85 +/- 0.05 at 3 months (P <.001) compared with 0.67 +/- 0.04 at baseline. In the high group, myocardial blood flow was 0.81 +/- 0.06 at 1 month and 0.83 +/-.04 at 3 months (P =.03) compared with 0.71 +/- 0.02 at baseline. No significant improvements in ischemia were demonstrated in any of the groups by dobutamine stress echocardiography at 1 or 3 months.


CONCLUSIONS
In porcine hibernating myocardium, intramyocardial basic fibroblast growth factor 2 significantly improved regional myocardial blood flow 3 months after treatment. There was no significant change in function in any of the 4 groups. These data suggest that intramyocardial dosing of basic fibroblast growth factor 2 (0.6 microg/kg) may be an optimal dose for improving perfusion in the treatment of end-stage coronary artery disease.
Biswas
Shankha S
SS
Division of Cardiothoracic Surgery, Duke University Medical Center, Durham, NC 27710, USA.
Hughes
G Chad
GC
Scarborough
John E
JE
Domkowski
Patrick W
PW
Diodato
Luis
L
Smith
Monica L
ML
Landolfo
Carolyn
C
Lowe
James E
JE
Annex
Brian H
BH
Landolfo
Kevin P
KP
D000704:Analysis of Variance; D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D015150:Echocardiography, Doppler; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D015552:Injections, Intralesional; D008297:Male; D017202:Myocardial Ischemia / Q000188:drug therapy* / Q000473:pathology; D015425:Myocardial Reperfusion / Q000379:methods*; D017682:Myocardial Stunning; D011336:Probability; D011897:Random Allocation; D012016:Reference Values; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D013556:Swine, Miniature; D014055:Tomography, Emission-Computed
D016222:Fibroblast Growth Factor 2