TRANSENDOCARDIAL AND TRANSEPICARDIAL INTRAMYOCARDIAL FIBROBLAST GROWTH FACTOR-2 ADMINISTRATION: MYOCARDIAL AND TISSUE DISTRIBUTION
Open Access
- 6 May 2005
- journal article
- research article
- Published by American Society for Pharmacology & Experimental Therapeutics (ASPET) in Drug Metabolism and Disposition
- Vol. 33 (8), 1101-1107
- https://doi.org/10.1124/dmd.104.002774
Abstract
Effective local delivery to the heart remains an obstacle to successful therapeutic application of a number of drugs and biological agents. This study was designed to study and optimize the delivery characteristics of transendocardial intramyocardial (IM) administration, determine myocardial deposition and retention over time, and compare it to transepicardial IM injection. Thirty-nine pigs were used for the study (15 for catheter optimization, 15 for transendocardial IM delivery, and 9 for transepicardial IM delivery). 125I-Fibroblast growth factor-2 (FGF2) (25 μCi) was used as the prototype molecule. Tissue and myocardial distribution was determined at 1 and 24 h and 7 days. Using 1-h 125I-FGF2 myocardial deposition as a parameter for delivery efficiency, the optimal needle length and delivery volume for transendocardial based delivery were determined to be 6 mm and 0.1 ml, respectively. Using these parameters for endocardial delivery, 125I-FGF2 cardiac activity was 18.01 ± 3.84% of delivered activity at 1 h, 11.65 ± 5.17% at 24 h, and 2.32 ± 0.87% at 7 days in ischemic animals. Studies in nonischemic animals produced similar results. For transepicardial delivery, 125I-FGF2 cardiac-specific activity was 23.14 ± 12.67% for the 6-mm needle, declining to 12.32 ± 8.50% at 24 h, and did not significantly differ from values obtained following transendocardial delivery. Thus, optimized transendocardial intramyocardial delivery using Biosense guidance results in efficient delivery of FGF2 to the target myocardium that is comparable with transepicardial delivery, both providing markedly higher myocardial deposition and retention and lower systemic recirculation of FGF2 than intracoronary, intrapericardial, or intravenous delivery. However, myocardial distribution is limited to injection sites.Keywords
This publication has 26 references indexed in Scilit:
- The VIVA TrialCirculation, 2003
- Intrapericardial administration of basic fibroblast growth factor: Myocardial and tissue distribution and comparison with intracoronary and intravenous administrationCatheterization and Cardiovascular Interventions, 2003
- Pharmacological Treatment of Coronary Artery Disease With Recombinant Fibroblast Growth Factor-2Circulation, 2002
- Electromagnetic guidance for catheter-based transendocardial injection: a platform for intramyocardial angiogenesis therapyJournal of the American College of Cardiology, 2000
- VEGF Improves Myocardial Blood Flow but Produces EDRF-Mediated Hypotension in Porcine HeartsJournal of Surgical Research, 1996
- Heparin Structure and Interactions with Basic Fibroblast Growth FactorScience, 1996
- Detection of Elevated Basic Fibroblast Growth Factor During Early Hours of in Vitro Angiogenesis Using a Fast ELISA ImmunoassayBiochemical and Biophysical Research Communications, 1994
- Vascular Endothelial Growth Factor in Ocular Fluid of Patients with Diabetic Retinopathy and Other Retinal DisordersNew England Journal of Medicine, 1994
- Basic fibroblast growth factor improves myocardial function in chronically ischemic porcine hearts.JCI Insight, 1994
- Salvage of Infarcted Myocardium by Angiogenic Action of Basic Fibroblast Growth FactorScience, 1992