A kinetic model of the circulatory regulation of tissue plasminogen activator during exercise, epinephrine infusion, and endurance training

Wayne L. Chandler, Wayne C. Levy, Richard C. Veith, John R. Stratton

Research output: Contribution to journalArticle

43 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)3293-3302
Number of pages10
JournalBlood
Volume81
Issue number12
DOIs
StatePublished - 1993

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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