Endothelial binding of recombinant tissue plasminogen activator:: Quantification in vivo using a recirculatory model

Binding of tissue plasminogen activator (t-PA) to the endothelium may be important in the prevention of thrombus formation. The aim was to develop a method to quantify endothelial binding in vivo. Nine healthy male volunteers received a 40 min continuous infusion with low dose recombinant t-PA (3.75 mug/min) and an indocycanine green infusion (0.5 mg/min) as control. A three-compartment recirculatory model was developed to account for non-specific circulatory delay effects. t-PA antigen, activity and t-PA/PAI-1 complex profiles showed a marked delay in increase at the beginning of the infusion. A reversible and concentration-dependent binding component was incorporated in the model which resulted in an accurate description of the t-PA concentration profile. t-PA binding was characterized by a dissociation constant of 5.9 ng/ml (SEM 1.8, CV 0%; fixed) and a binding capacity of 70 mug t-PA (SEM 10, CV 48%). This model can be used as a tool to quantify the ability of the endothelium to bind t-PA.