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A kinetic model of the circulatory regulation of tissue plasminogen
activator during exercise, epinephrine infusion, and endurance training
WL Chandler, WC Levy, RC Veith and JR Stratton
Department of Laboratory Medicine, University of Washington, Seattle 98195.
A computer simulation of the circulatory system was used to kinetically
model secretion, inhibition, and clearance of tissue plasminogen activator
(t-PA) during three different processes that increase active t-PA levels:
epinephrine infusion, exercise, and endurance training. Infusion of
epinephrine stimulated an increase in t-PA secretion that was proportional
to the plasma epinephrine concentration. In addition, epinephrine infusion
increased hepatic blood flow and t-PA clearance, thus slowing the increase
of plasma t-PA levels. During exercise, t-PA levels increased due both to
increased t-PA secretion and to decreased clearance secondary to reduced
hepatic blood flow. The increase in t-PA secretion during exercise was
directly proportional to the epinephrine concentration in blood with the
same ratio of t-PA secretion to epinephrine as found during epinephrine
infusion, suggesting that increased plasma epinephrine during exercise was
the primary stimulus for t-PA secretion. Lastly, the simulation predicted
that 6 months of endurance training produced a decrease in resting
plasminogen activator inhibitor type 1 (PAI-1) secretion, resulting in less
t-PA inhibition and an overall increase in active t-PA after training.
Accurate analysis of the regulation of active t-PA levels in blood required
simultaneous modeling of t-PA and PAI-1 secretion, hepatic clearance, and
inhibition of t-PA by PAI-1.
Volume 81,
Issue 12,
pp. 3293-3302,
06/15/1993
Copyright © 1993 by The American Society of Hematology
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