The Fate of Intravenously Administered bFGF and the Effect of Heparin

Abstract

The fate and effects of intravascular bFGF are unknown. We have investigated the fate of bFGF administered intravenously to rats in the presence and absence of heparin, and evaluated the effect of a 3-day IV infusion of bFGF on proliferation of endothelial and vascular smooth muscle cells in situ. [¹²⁵I]bFGF, administered as an IV bolus, was rapidly cleared from the circulation (t_1/2 = 1.5 min) by the liver. Nevertheless, it was maintained at a constant, predictable concentration in the blood (9.7 ± 4% of the amount infused) by continuous IV infusion. Heparin consistently altered the pattern: slowing the rate of clearance (t_1/2 = 4.5 min), increasing the plateau concentration in the blood during continuous infusion (32.5 ± 14.3% of the amount infused), and allowing intact (as determined by gel analysis) bFGF to cross from the circulation into the urine. A 3-day infusion of bFGF alone (2.5 ng/kg/min) and with adenosine (11.6 μM/kg/hr) did not increase [³H]thymidine incorporation in either endothelial cells or vascular smooth muscle cells, suggesting that they are refractory to this factor when it is administered intravascularly.

Key Words:

• bFGF
• Heparin
• endothelial cells
• Kupffer cells
• vascular smooth muscle cells
• pharmacokinetics
• intravenous
• growth factor