Intrapericardial administration of basic fibroblast growth factor: Myocardial and tissue distribution and comparison with intracoronary and intravenous administration

• Published in: Catheterization and cardiovascular interventions 2003-03, Vol.58 (3), p.375-381
• Main Authors: Laham, Roger J., Rezaee, Mehrdad, Post, Mark, Xu, Xunyu, Sellke, Frank W.
• Format: Article
• Language: English
• Subjects: angiogenesis; Animals; Autoradiography; basic fibroblast growth factor; Disease Models, Animal; Female; Fibroblast Growth Factor 2 - administration & dosage; Fibroblast Growth Factor 2 - pharmacokinetics; Fibroblast Growth Factor 2 - therapeutic use; Heart - diagnostic imaging; Heart - drug effects; Injections; Injections, Intravenous; Instillation, Drug; Male; Myocardial Ischemia - diagnostic imaging; Myocardial Ischemia - drug therapy; pericardial delivery; Pericardium - diagnostic imaging; Pericardium - drug effects; Radiography; Swine; tissue distribution; Tissue Distribution - drug effects
• ISSN: 1522-1946; 1522-726X
• DOI: 10.1002/ccd.10378

Growth factor‐induced angiogenesis is being investigated in ischemic heart disease. Intracoronary and intravenous delivery are the most practical, but are limited by low myocardial uptake and significant systemic recirculation. The pericardial space may act as a drug delivery reservoir with increased myocardial uptake and reduced systemic toxicities. This study was designed to investigate the myocardial and tissue deposition and retention of basic fibroblast growth factor (FGF‐2) after intrapericardial administration in normal and chronically ischemic animals. Twelve Yorkshire pigs were used for the study [six normal and six animals with chronic myocardial ischemia (ameroid constrictor on LCx)] with bolus intrapericardial administration of 125I–FGF‐2 (25 μCi) with 30 μg of cold FGF‐2 and 3 mg of heparin. Tissue and myocardial distribution was determined at 1 and 24 hr by measuring 125I‐bFGF–specific activity. In addition, regional myocardial deposition was determined using 125I‐bFGF activity and organ level autoradiography. The heart (pericardium and myocardium) accounted for the majority of 125I‐bFGF activity in ischemic animals (30.9% at 1 hr and 23.9% at 24 hr). Left anterior descending artery territory activity/gm of tissue for nonischemic and ischemic animals was 0.01% and 0.01% at 1 hr and 0.0009% and 0.12% at 24 hr, respectively. LCx territory activity for nonischemic and ischemic animals was 0.006% and 0.008% at 1 hr and 0.03% and 0.05% at 24 hr, respectively. Endocardial activity was low at all time points. Liver uptake was 0.47% (nonischemic) and 0.34% (ischemic) at 1 hr and 0.23% (nonischemic) and 0.54% (ischemic) at 24 hr. Intrapericardial delivery of FGF‐2 provides markedly higher myocardial deposition and retention and lower systemic recirculation than intracoronary or intravenous delivery at the expense of poor subendocardial penetration. This limitation, however, did not affect its efficacy. Cathet Cardiovasc Intervent 2003;58:375–382. © 2003 Wiley‐Liss, Inc.