Intracoronary and intravenous administration of basic fibroblast growth factor: myocardial and tissue distribution.
Therapeutic angiogenesis using various heparin-binding growth factors is a promising treatment for ischemic heart disease. Single dose intracoronary (IC) or i.v. delivery are most practical for clinical use. This study was designed to investigate the myocardial and tissue deposition of basic fibroblast growth factor (bFGF) after IC and i.v. administration in normal and chronically ischemic animals. Twenty-four Yorkshire pigs were used (12 normal and 12 ischemic animals) with IC and i.v. administration of 125I-bFGF (25 microCi) combined with cold bFGF (30 microg) and heparin (3 mg). Tissue and myocardial distribution was determined at 1 and 24 h by measuring 125I-bFGF specific activity and by organ and light level autoradiography. The liver accounted for the majority of 125I-bFGF activity at 1 h (37.6 +/- 17.1% for IC and 42.1 +/- 17.7% for i.v. delivery), with a reduction to 2.8 +/- 1.5% for IC and 1.5 +/- 0.9% for i.v. delivery by 24 h. Total cardiac specific activity at 1 h was 0.88 +/- 0.89% for IC and 0.26 +/- 0.08% for i.v. administration (p =.12) and decreased to 0.05 +/- 0.04% (p =.05, versus 1 h) and 0. 04 +/- 0.01% (p <.001, versus 1 h) at 24 h, respectively. IC but not i.v. delivery resulted in higher deposition in ischemic than normal myocardium. IC delivery resulted in enhanced bFGF deposition only in myocardial territories subtended by the infused artery. Intravenous delivery compares favorably with IC delivery with a 3- to 4-fold reduction in myocardial deposition at 1 h and with similar solid organ deposition. The less invasive nature of i.v. delivery, its potential for repeat administration, and its applicability to a larger population may offset its resultant reduced myocardial deposition. Efficacy studies are ongoing.
Laham
R J
RJ
Angiogenesis Research Center, Department of Medicine, Harvard Medical School, and Beth Israel Deaconess Medical, Boston, MA 02215, USA. rlaham@caregroup.harvard.edu
Rezaee
M
M
Post
M
M
Sellke
F W
FW
Braeckman
R A
RA
Hung
D
D
Simons
M
M
D000818:Animals; D004333:Drug Administration Routes; D016222:Fibroblast Growth Factor 2 / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics / Q000652:urine; D006321:Heart; D007262:Infusions, Intravenous; D007668:Kidney / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D013552:Swine; D014018:Tissue Distribution
D016222:Fibroblast Growth Factor 2