Delayed Incorporation of [75Se]Selenomethionine into Fibrinogen: Its Effect upon Kinetic Studies of Fibrinogen with [75Se]Selenomethionine in Rabbits

Summary . When data-points on the descending phase of autoendogenous plasma [^75Se]selenomethionine-fibrinogen (⁷⁵SeM-fibrinogen) radioactivity curves in rabbits were expressed as per cent of maximum radioactivity, they could be fitted to single exponential curves both in controls and in animals with enhanced fibrinogen synthesis from multiple causes. Intravascular half-disappearance times (HDTs) determined from these slopes were inversely related to maximum per cent incorporation of ⁷⁵SeM into fibrinogen (r= 0.662, P<0.001). The mean HDT for 17 controls was 112 hr, whereas the mean HDT for animals with marked stimulation of fibrinogen production was close to 56 hr, the value for the mean HDT for the second slope of fibrinogen radioactivity in 13 normal recipient rabbits injected with donor ⁷⁵SeM-fibrinogen. Two kinetic compartmental models were proposed to account for the marked difference between the autoendogenous ⁷⁵SeM-fibrinogen decay slope of control animals and the second slope of fibrinogen radioactivity in recipient animals. Both models account for a random, delayed input from the liver of ⁷⁵SeM-fibrinogen, which decreases when fibrinogen synthesis is stimulated. In one model, the delay occurs before synthesis of labelled fibrinogen, whereas in the other model the delay occurs after synthesis of labelled fibrinogen. Both models indicate that in control animals only about 50% of ⁷⁵SeM-fibrinogen enters the plasma from the liver without delay. In contrast, in rabbits with ACTH-stimulated fibrinogen production, over 80% of ⁷⁵SeM-fibrinogen enters the plasma without delay. Although both models fit the kinetic data, a steady state calculation for the model in which delay occurs after synthesis of labelled fibrinogen molecules gives a size for the intracellular fibrinogen delay pool in the liver which exceeds the size for the plasma fibrinogen pool. Therefore, this model seems untenable. Our evidence of a marked effect of variation in delayed input of ⁷⁵SeM-fibrinogen upon the degradation phase of the autoendogenous fibrinogen radioactivity curve raises doubts about the validity of using isolated portions of such curves for separate estimations of fibrinogen synthesis and catabolism.