title: In vivo tissue distribution of fibroblast growth factor-1 after intraarterial delivery.
abstract: The clinical applicability of fibroblast growth factor-1 (FGF-1) plus heparin delivery in optimizing the healing of both autogenous vein and synthetic vascular grafts has been suggested. The authors have reported enhanced endothelial cell proliferation, concurrent increased capillarization, and minimal intimal hyperplasia using suspensions of FGF-1 and heparin impregnated onto expanded polytetrafluoroethylene grafts. The current study characterizes the tissue distribution of 125I-FGF-1 delivered by continuous intraarterial infusion. 125I-FGF-1 delivered by continuous intraarterial infusion. 125I-FGF-1 (1.1 ng) and heparin (28 U) were continuously infused into the thoracic aorta via the proximal end of the ligated left carotid artery for 24 hr in four New Zealand white rabbits using an Alzet (Alza Corp., Palo Alto, CA) osmotically activated pumping device. Rabbits were sacrificed after 24 hr, exsanguinated, and biopsies taken from the liver, kidneys, spleen, lungs, heart, thyroid gland, muscle, and fat. These samples were assayed for radioactivity and results expressed as cpm 125I/gram of both wet and dry weight of tissue. 125I-FGF-1 uptake (cpm/g dry wt.) was greatest in the thyroid (551.1 +/- 131.4). This was 2.5-5.5 x greater (p < or = 0.01) than those organs with intermediate uptake (lungs, liver, kidneys, spleen, and heart). Lowest uptake was noted in the blood, muscle, and fat. A similar distribution pattern was found in wet weight comparisons. Total organ 125I-FGF-1 content was greatest in the liver at 818.1 +/- 176.3 cpm (p < or = 0.002) and intermediate in the lungs (204.7 +/- 38.5 cpm) and kidneys (191.2 +/- 11.9 cpm). Although no FGF-1-induced toxicity has yet been reported, these results will allow for future tissue-specific toxicology studies before clinical trials.
authors.affiliation: Department of Surgery, Loyola University Medical Center, Maywood, IL 60153, USA.
authors.forename: M K
authors.initials: MK
authors.lastname: Hirko
authors.forename: P H
authors.initials: PH
authors.lastname: Lin
authors.forename: C
authors.initials: C
authors.lastname: Gosselin
authors.forename: D
authors.initials: D
authors.lastname: Ren
authors.forename: H P
authors.initials: HP
authors.lastname: Greisler
mesh_terms: D000818:Animals; D001807:Blood Vessel Prosthesis; D004730:Endothelium, Vascular / Q000187:drug effects / Q000254:growth & development; D005260:Female; D005346:Fibroblast Growth Factors / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D006493:Heparin / Q000008:administration & dosage; D015918:Infusion Pumps, Implantable; D007261:Infusions, Intra-Arterial; D007457:Iodine Radioisotopes; D011817:Rabbits; D014018:Tissue Distribution; D014945:Wound Healing / Q000187:drug effects
chemical_list: D007457:Iodine Radioisotopes; D005346:Fibroblast Growth Factors; D006493:Heparin