Intracoronary administration of FGF-2: a computational model of myocardial deposition and retention

Renee J. Filion, Aleksander S. Popel
2005 American Journal of Physiology. Heart and Circulatory Physiology  
Filion, Renee J. and Aleksander S. Popel. Intracoronary administration of FGF-2: a computational model of myocardial deposition and retention. This study uses a computational model to characterize the myocardial deposition and retention of basic fibroblast growth factor (FGF-2) at the cellular level after intracoronary (IC) administration of exogenous FGF-2. The model is applied to the in situ conditions present within the myocardium of a dog for which the plasma pharmacokinetics resulting from
more » ... IC injection of FGF-2 were recorded. Our estimates show that the processes involved in FGF-2 signaling are not diffusion limited; rather, the response time is determined by the reaction time of FGF-2 binding to cell surface receptors. Additionally, the processes of receptor secretion and internalization are found to play crucial roles in the FGF-2 dynamics; future experiments are required to quantify these processes. The model predictions obtained in this study suggest that IC administration of FGF-2 via either a single bolus or repetitive injections causes a transient increase (time scale of hours) in myocardial FGF-2 concentration if the endogenous level of free interstitial FGF-2 is low enough to allow permeation of FGF-2 molecules from the microvascular to the interstitial spaces. The model shows that the majority (64%) of the extracellular FGF-2 ligands are located within the interstitium, and similar fractions are found in the basement membrane and extracellular matrix. Among the FGF-2 molecules found within the interstitium, 2% are free and 98% are bound to interstitial heparan sulfate proteoglycans. These results support the theory of extracellular control of the bioavailability of FGF-2 via dynamic storage of FGF-2 within the basement membrane and extracellular matrix. basic fibroblast growth factor; mathematical; compartmental; angiogenesis; drug delivery Address for reprint requests and other correspondence: A. S. Popel,
doi:10.1152/ajpheart.00205.2004 pmid:15331374 fatcat:46l5h5tj7zggba74vm5i2ogy4q